Summary— Introduction: HIV (human immunodeficiency virus) is a virus that attacks and destroys one type of white blood cell in particular, the CD4 lymphocytes, which are responsible for the body's immune response. This weakens the immune system to such an extent that it can no longer fight other viruses, bacteria, protozoa, fungi and tumours. Methods: We investigated the potential biological role of the natural compound Polydatin (or piceid) using SwissDock, a web service to predict the molecular interactions that can occur between a target protein and a small molecule. Discussion: For the first time, we have investigated the role of polydatin against HIV-1 protease and HIV-2 protease through a computational approach by comparing their estimated ΔG values (kcal/mol) and the nature of the interactions between the residues in the catalytic centre of the HIV proteases.Conclusion: From these simulations, Polydatin has excellent physical properties and an excellent estimated ΔG value (kcal/mol) of about -9.9 kcal/mol against HIV-2 protease and ΔG value (kcal/mol) of about -9.5 kcal/mol against HIV-1 protease. In addition, Polydatin was able to bind to two key amino acids of the catalytic triad sequence common to asparagine proteases (Asp25 and Gly27)

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02-restricted CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope exclusively restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.

We investigated differences in mpox clinical outcomes in people with HIV (PWH) and without HIV (PWoH) and the impact of vaccination in Catalonia, Spain. We used surveillance data and the PISCIS HIV Cohort. We included all confirmed mpox cases (May-December 2022). Of 2122 mpox cases, the majority had mild disease, 56% were Spanish, and 24% from Latin-America. Forty percent were PWH, with median CD4+T-cell 715 cells/µL, 83% had HIV-RNA<50 copies/ml and 1.8% CD4+T-cell<200 cells/L. PWH had no increased risk for complications, except in cases of immunosuppression. PWH with CD4+T-cell<200 cells/µL were more likely to be from Latin-America, had more generalized exanthema, and required hospitalization more frequently (p=0.001). Diagnosis of other sexually transmitted infections (STIs) was common, both at mpox diagnosis (17%) and 2 years before (43%). Dose-sparing smallpox vaccination was accompanied by a sharp decrease in mpox incidence in both populations (p<0.0001). In conclusion, PWH were not at increased risk of severe disease or hospitalization unless immunosuppressed. Mpox is a marker of high-risk sexual behavior and was associated with high HIV and STI rates, supporting the need for screening in all mpox cases. Ethnicity disparities underscore the need for interventions to ensure equitable healthcare access. Dose-sparing smallpox vaccination retained effectiveness.

Introduction: This study aimed to identify factors associated with late diagnosis and clinically monitor newly diagnosed HIV/AIDS patients. Method: Retrospective longitudinal study, based on secondary data from a specialized unit at a tertiary hospital. Data collection included sociodemographic, behavioral, clinical, and laboratory data of newly diagnosed HIV patients between 2015-2019. Data analysis adopted inferential statistical tests using the SPSS program, considering α ≤ 0.05. Results: 314 individuals were newly diagnosed with HIV/AIDS. 70.3% (208) had a late diagnosis, and 57.1% (169) were diagnosed very late. There was an association of the very late diagnosis with the variables sex and education and with origin, entry, occurrence of opportunistic diseases, use of ARV therapy, and death, associated with late and very late diagnosis, respectively. The results of the regression model indicate that males had 2.28 [95% CI 1.11 - 4.46] higher chances of having a late diagnosis compared to females. Conclusions: This study evidenced a high prevalence of late and very late diagnoses in newly diagnosed male HIV patients who presented with opportunistic diseases, requiring hospitalization, and having a significant risk of progressing to death.

HIV/AIDS infection increases vulnerability to ill-health states and has a major impact on the general health status. This study aims to describe Angolan adolescents and adults’ comprehensive knowledge of HIV/AIDS and its associated factors based on the 2016 demographic and health survey (DHS). Data from 19,785 individuals between the ages of 15 and 49 years old, who re-sponded to all the DHS questions between October 2015 and March 2016 were included in this study. Multivariable analysis using logistic regression was used to compute the adjusted odds ratio and respective 95% confidence intervals. In Angola, 47.7% of the respondents had general com-prehensive knowledge of HIV/AIDS. The odds of having comprehensive knowledge about HIV/AIDS were higher among individuals who watch television (aOR: 2.40; 95% CI: 2.11, 2.72) or read journals and magazines (aOR: 1.99; 95% CI: 1.72, 2.30) more than once a week and, people with primary or higher-level education (aOR: 1.83; 95% CI: 1.67, 2.00). Similarly, for people living in urban areas (aOR: 1.51; 95% CI: 1.34, 1.71). These results may reflect important inequities and can assist decision-makers in advocating to continue to invest in health literacy for HIV but also in the development of tailored interventions in this area.

(1) Background: The HIV subtype D is generally associated with a faster decline in CD4+ T cell counts, a higher viral load, and a faster progression to AIDS. However, it is still poorly characterized in Brazil. In this study, we used genomics and epidemiological data to investigate the transmission dynamics of HIV subtype D in the state of Bahia, Northeast Brazil. (2) Methods: to achieve this goal, we obtained four novel HIV-1 subtype D partial pol genome sequences using the Sanger method. To understand the emergence of this novel subtype in the state of Bahia, we used phylodynamic analysis on a dataset comprising 3,704 pol genome sequences downloaded from the Los Alamos database. (3) Results: Our analysis revealed three branching patterns, indicating multiple introductions of the HIV-1 subtype D in Brazil from the late 1980s to the late 2000s and a single introduction event in the state of Bahia. Our data further suggest that these introductions most likely originated from European, Eastern African, Western African and Southern African countries. (4) Conclusion: Understanding the distribution of HIV-1 viral strains and their temporal dynamics is crucial for monitoring the real-time evolution of circulating subtypes and recombinant forms, as well as for designing novel diagnostic and vaccination strategies. We advocate for a shift to active surveillance, to ensure adequate preparedness for future epidemics mediated by emerging viral strains.

Background: Human papillomavirus (HPV) is responsible for most cervical cancer cases globally, with women living with HIV at higher risk of persistent HPV infection and HPV-associated disease. The HPV vaccine is a promising solution to reducing cervical cancer rates, but its uptake among women living with HIV in Nigeria is unknown. Methods: A facility-based, cross-sectional survey was conducted with 1,371 women living with HIV to assess their knowledge of HPV, cervical cancer, and the HPV vaccine, as well as their willingness to pay for the vaccine at the HIV treatment clinic, Nigerian Institute of Medical Research, Lagos. Willingness to pay for the HPV vaccine was also assessed. Multivariable logistic regression models were developed to identify factors associated with willingness to pay for the HPV vaccine. Results: The study found that 79.1% of participants had not heard of the vaccine, and only 29.0% knew of its efficacy in preventing cervical cancer. Moreover, 68.3% of participants were unwilling to pay for the vaccine, and the average amount they were willing to pay was low. Knowledge of HPV, the HPV vaccine, cervical cancer, and income were factors associated with willingness to pay for the vaccine. Health workers were the primary source of information. Conclusion: The study found that 79.1% of participants had not heard of the vaccine, and only 29.0% knew of its efficacy in preventing cervical cancer. Moreover, 68.3% of participants were unwilling to pay for the vaccine, and the average amount they were willing to pay was low. Knowledge of HPV, the HPV vaccine, cervical cancer, and income were factors associated with willingness to pay for the vaccine. Health workers were the primary source of information.

Globally, non-communicable diseases like hypertension are on the rise, existing concurrently with the human immunodeficiency virus (HIV) in populations, especially those in low- to middle-income countries. The introduction of antiretroviral treatment (ART) for people living with HIV was welcomed with great enthu-siasm across populations. A cross-sectional study of 100 purposively selected adult participants on an-tiretroviral treatment living in the OR Tambo district was conducted to determine factors associated with treatment outcomes among patients living with HIV and hypertension comorbidity. The data was analyzed using the Statistical Package for Social Sciences, with a p-value of 0.05 considered significant. A total of 86% of the female population, with a mean age of 39.76, was studied. Participants with improved viral load and CD4 cell count after initiation of ART increased from 63% to 68% and 74% to 90%, respectively whilst viral load suppression increased from 45.1% to 90.2%. Hypertension post-ART initiation increased from 9% to 34%, exacerbated by smoking (12%), alcohol (14%), vegetable consumption (39%), skipping breakfast (50%), sugar use (62%), and vigorous physical activity (12%). The onset of hypertension was linked to the start of ART, and risky behaviors influenced treatment outcomes. Primordial prevention, like strong health promotion inter-ventions for risk factors, is needed to improve life expectancy.

TB and HIV continue to increase and constitute major public health concerns worldwide, mainly in resource-limited countries, showing that we are not going to end HIV if we do not also end TB. Herein, we investigated the risk factors related to HIV infection among TB patients in Luanda, the capital city of Angola. This was a retrospective cohort study conducted on the medical records of 117 TB patients from January to September 2016. Overall, the HIV/TB co-infection rate was 12%. The mean age of coinfected patients was 37.7±10.1 years. No statistically significant relationship was observed between sociodemographic or clinical features with HIV/TB co-infection (p>0.05). TB patients aged 30 years or older (OR: 4.13, p=0.072), female (OR: 1.08, p=0.898), residing in urbanized areas (OR: 1.90, p=0.578), with a history of treatment abandonment (OR: 3.74, p=0.083), with polyresistance (OR: 1.62, p=0.603), and MDR-TB (OR: 2.00, p=0.454), were more likely to have HIV/TB co-infection, while latent TB infection (OR: 0.63, p=0.559) and treatment-susceptible TB patients (OR: 0.56, p=0.616), presented a lower chance of HIV/TB coinfection. Our finding showed a slightly high HIV/TB coinfected rate, which suggests that the dual HIV/TB epidemic keeps evolving and poses a huge concern to the public health in Angola. Further studies on features related to HIV/TB coinfection and its impact on disease progression and clinical outcome in adults from high-risk Angolan communities, should be carried out to intensify and strengthen collaborative activities between national TB and HIV programs in Angola.

HIV-1 protease (PR) is a viral enzyme that cleaves viral polyprotein precursors to convert them into functional forms, a process essential to generate infectious viral particles. Due to its broad substrate specificity, HIV-1 PR can also cleave certain host cell proteins. Several studies have identified host cell substrates of HIV-1 PR and described the potential impact of their cleavage on HIV-1-infected cells. Of particular interest is the interaction between PR and the caspase recruitment domain-containing protein 8 (CARD8) inflammasome. While PR typically has low levels of intracellular activity prior to viral budding, induction of premature PR activation to trigger CARD8-mediated cell killing may help eliminate latent reservoirs in people living with HIV. In this review, we discuss the viral and host substrates of HIV-1 protease and highlight potential applications and advantages of targeting CARD8 sensing of HIV-1 PR.

Introduction: Established predictors for COVID-19 related mortalities are diverse, with cytokine release syndrome (CRS), a key intermediator to the case fatalities being dominant and multi-faceted. The impact of these several risk factors on coronavirus mortality have been previously reported in several meta‐analyses limited by small sample sizes and premature data, and CRS not fully being accounted for. The objective of this systematic review and meta-analysis was to evaluate the evidence on the risk of COVID-19 related CRS and mortality with HIV serostatus using published data, and a meta-regression to account for possible covariates. Method: Electronic databases including Google Scholar, Cochrane Library, Web of Sciences (WOS), EMBASE, Medline/PubMed, COVID-19 Research Database, and Scopus, were systematically searched till 30th February, 2022. All human studies were included irrespective of publication date or region. Twenty-two studies with a total of 19,783,097 patients detailing COVID-related mortality and eleven with a total of 2,005,274 were included. To pool the estimate, a random-effects model with risk ration as the effect measure was used. Moreover, publication bias and sensitivity analysis were evaluated followed by meta-regression. The trial was registered (CRD42021264761) on the PROSPERO register. Results: The findings were consistent in stating the contribution of HIV infection for COVID-19 related CRS and mortality. The cumulative COVID-19 related mortality and CRS was 110270 (0.6%) and 48863 (2.4%) with total events of 2010 (3.6%), 108260 (0.5%) and 837(4.6%), 48026 (2.4%) among HIV-positive and negative persons respectively. HIV infection showed an increased risk of COVID-19 related CRS and mortality [RR= 1.48, 95% CI (1.16, 1.88) (P=0.002)] and [RR =1.19, 95% CI (1.02 -1.39) (P=0.00001)] respectively, both with substantial heterogeneity (I² > 80%). The true effects size in 95% of all the comparable populations fell between 0.64 to 2.22 and 0.67 to 3.29 for mortality and CRS respectively. MC studies and COVID-19 mortality with HIV infection showed a significant association [RR = 1.305, 95% CI (1.092 -1.559) (P = 0.003)], similar to studies conducted in America (RR = 1.422, 95% CI 1.233–1.639) and South Africa (RR = 1.123, 95% CI 1.052–1.198). HIV infection showed a risk for ICU admission [(P=0.00001) (I² = 0%)] and mechanical ventilation [(P=0.04) (I² = 0%)] as parameters of CRS. Furthermore, risk of COVID-19 related CRS is influenced by the year a study was conducted (R² = 0.55) and the region (R² = 0.11) same for mortality (R² = 0.60). The variance proportion explained by covariates was significant for CRS (I² = 86.5%, Q = 73.99, df = 10, P = 0.0000) (R² = 0.78) and mortality (I² = 87.5%, Q = 168.02, df = 21, p = 0.0000) (R² = 0.67). Conclusion: Our updated meta-analysis indicated that HIV infection was significantly associated with an increased risk for both COVID-19 – CRS and mortality, which might be modulated by regions, study setting and year. Risk for ICU admission and mechanical ventilation are the key indicators of CRS. We believe the updated data further anchoring CRS will contribute to more substantiation of the findings reported by similar earlier studies (Dong et al., 2021; K. W. Lee et al., 2021; Massarvva, 2021; Mellor et al., 2021; Ssentongo et al., 2021)

HIV-1 Nef is a multifunctional protein with well-known lethal properties. HIV infects various cells from the brain compartment and expressed nef is responsible for developing neuropathogenic potential. HIV-infected glial cells express nefvirotoxinand stimulate the cascade of various pathways to activate uninfected cells to release neurotoxic elements damaging cells themselves. A lot of genetic variabilities of this protein have been reported from patients with HIV-associated neurocognitive disorders. To determine the neurotoxic potential of subtype-specific nef plasmids and nef plasmids of clinical samples with and without HAND were transfected in normal human astrocytes (NHA) and monocyte-derived macrophages (MDM) using nef-pCMV-HA plasmid constructs. Supernatants from subtype-specific Nef plasmids indicated the upregulation of proinflammatory cytokines. The induced expression might be due to the nef genetic variability or variations in the transfection efficiency and expression levels of nef.The mRNA expression of IL-6, IP-10, and TNF-α indicated upregulation of 5.0-fold in NHA and 3-fold in MDM with respect to empty vector control transfection. Further, the kynurenine metabolites were also assessed from culture supernatants of NHA and MDM indicating the upregulation of IDO and KYNU in NHA by 3.0-fold and 3.2-fold in MDM.The expression levels of nef and cytokines at the translational level were confirmed by western blotting and bio-plex Pro cytokine estimation assay respectively along with controls expressing green fluorescent protein (GFP).The oxidative stress was also found to be elevated as compared to control cells as determined by the estimation of nitric oxide from the culture supernatant to confirm the neurotoxic potential of HIV nef plasmids. The downregulation in the levels of cytokines, as well as kynurenine metabolites, was observed in culture supernatants after blocking the expression of nef using HIV nef siRNA. Phylogenetic analysis of Nef sequences indicated subtype C predominance except one sequence showing the partial sequence of HIV-1 subtype B sequence forming BC recombinantThe upregulation in the cytokine and pathway-specific metabolites might be linked with the neurotoxic potential of HIV-1 Nef leading to neuropathogenesis. In conclusion, the variation in the transfection efficiency, nef expression levels, and the genetic variability of Nef might be responsible for upregulating the expression levels of cytokines and kynurenine metabolites in astrocytes and MDM.

Background: Objectives were to determine the real-life effectiveness and safety of DT with dolutegravir (50 mg/QD) plus lamivudine (300 mg/QD) in multiple-tablet regimen (MTR) in naïve PLHIV followed up for 48 weeks and to evaluate the compliance and satisfaction of patients. Material and methods: Open, single-arm, multicenter, non-randomized clinical trial from May 2019 through September 2020 with 48-week follow-up. Results: The study included 88 PLHIV (91% male) with mean age of 35.9 years; 76.1% were MSM. Mean baseline CD4 was 516.4 cells/uL, with viral load (VL) of 104,828 cop/mL, and 11.4% were in AIDS stage. DT started within 7 days of first specialist consultation in all patients and the same day in 84.1%; 3.4% had baseline resistance mutations (K103N, V106I+E138A, and V108I); 12.5% were lost to follow-up. At week 48, 86.3% had VL< 50 cop/uL by intention-to-treat analysis and 98.7% by per-protocol (PP) analysis. Virological failure (VF) was recorded in 1.1%, with no resistance mutation. One blip was detected in 5.2%, without VF. Three reported anxiety, dizziness, and cephalgia, respectively, at week 4 and one insomnia at week 24; none reported adverse events at week 48. Mean weight was 4 kg higher at 48 weeks (p=0.0001) and abdominal circumference 3 cm larger at 24 weeks (p=0.022). No forgetfulness occurred in 98.7% of patients. Patient satisfaction was 90/100 at 4, 24, and 48 weeks. Conclusion: Real-world data demonstrate that dolutegravir plus lamivudine in MTR is effective, safe, and satisfactory, moderately increasing weight and abdominal circumference and administrable on a test-and-treat strategy.

Several factors enhance the possibility of vertical HIV transmission in the pediatric population. Unfortunately, the data of the prevalence of HIV and associated risk factors in these populations remain limited in Rwanda. The study aimed to assess HIV prevalence and risk factors for infants born to mothers on ARV treatment at CHUB/Rwanda. MethodsA cross-sectional study was carried out on infants who were born to mothers under ARV treatment at CHUB. The associated risk factors were retrospectively assessed using prevention vertical HIV transmission records, and Dried Blood spots (DBS) were prospectively tested using Polymerase Chain Reaction (PCR). Data were analyzed by logistic regression. Ethical clearance (Ref: CMHS/IRB/198/2017) was issued by University of Rwanda to fulfill research ethical consideration.ResultsAmong 185(100%) infants born to HIV-positive mothers under ARV treatment, 5(2.7%) were HIV positive. The most associated risk factors were increased to over 1log copies/ml mother’s viral load (OR 9.3, 95% CI 1.01-85.45, P= 0.04) and mother’s CD4 count lower than 350 cells/µl (OR 6.4, 95% CI 1.03-40.06, P=0.04). The factors found to reduce the rate of vertical transmission of HIV were health facility as a delivery place (P=0.03), exclusive breastfeeding for 6 months (P= 0.006), and attending the antenatal care (P=0.01) while feeding children and vaginal delivery were associated risks but not statistically significant.ConclusionThe current study supports that the more mothers’ viral load and CD4 count decrease, so does the risk of HIV to their infants. A fact which indicates that both prevalence and risk factors remain an alarming issue. Much effort and multi-disciplinary approach are highly recommended.

Despite widespread use of combined antiretroviral therapy (cART) and increased life expectancy in people living with HIV (PLWH), HIV-related lymphomas (HRL) remain a leading cause of cancer morbidity and mortality for PLWH, even in patients optimally treated with cART. While incidence of aggressive forms of non-Hodgkin lymphoma decreased after cART advent, incidence of Hodgkin lymphoma (HL) has increased among PLWH in recent decades. The coinfection of Epstein Barr virus plays a crucial role in the pathogenesis of HL in the HIV setting. Currently, PLWH with HRL, including HL, are treated similarly to HIV-negative patients and, importantly, the prognosis of HL in PLWH is approaching to that of the general population. In this regard, effective chem-otherapy is strongly recommended since it has been shown to improve survival rates in all lymphoma subtypes, including HL. As a consequence, interdisciplinary collaboration between HIV specialists and hemato-oncologists for the management of potential drug-drug interactions and overlapping toxicities between antiretroviral and antineoplastic drugs is crucial for the op-timal treatment of PLWH with HL. In this article the authors review and update the epidemio-logical, clinical and biological aspects of HL presenting in PLWH with special emphasis in the improvement on prognosis and the factors that have contributed to it.

Despite widespread use of combined antiretroviral therapy (ART) and increased life expectancy in people living with HIV (PLWH), HIV-related lymphomas (HRL) remain a leading cause of cancer morbidity and mortality for PLWH, even in patients optimally treated with ART. While incidence of aggressive forms of non-Hodgkin lymphoma decreased after ART advent, incidence of Hodgkin lymphoma (HL) has increased among PLWH in recent decades. The coinfection of Epstein Barr virus plays a crucial role in the pathogenesis of HL in the HIV setting. Currently, PLWH with HRL, including HL, are treated similarly to HIV-negative patients and, importantly, the prognosis of HL in PLWH is approaching to that of the general population. In this regard, effective chemotherapy is strongly recommended since it has been shown to improve survival rates in all lymphoma subtypes, including HL. As a consequence, interdisciplinary collaboration between HIV specialists and hemato-oncologists for the management of potential drug-drug interactions and overlapping toxicities between antiretroviral and antineoplastic drugs is crucial for the optimal treatment of PLWH with HL. In this article the authors review and update the epidemiological, clinical and biological aspects of HL presenting in PLWH with special emphasis in the improvement on prognosis and the factors that have contributed to it.

HIV-associated neurocognitive disorders (HAND) persist under antiretroviral therapy as a complex pathology that has been difficult to study in cellular and animal models. Therefore, we generated an ex vivo human brain slice model of HIV-1 infection from surgically resected adult brain tissue. Brain slice cultures processed for flow cytometry showed >90% viability of dissoci-ated cells within the first three weeks in vitro, with parallel detection of astrocyte, myeloid, and neuronal populations. Neurons within brain slices showed stable dendritic spine density and mature spine morphologies in the first weeks in culture, and they generated detectable activity in multi-electrode arrays. We infected cultured brain slices using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs) that were exposed to a GFP-expressing R5-tropic HIV-1 in vitro. Infected slice cultures expressed viral RNA and developed a spreading infection up to 9-days post-infection, which were significantly decreased by antiretrovirals. We also detected infected myeloid cells and astrocytes within slices and observed minimal effect on cellular via-bility over time. Overall, this human-centered model offers a promising resource to study the cel-lular mechanisms contributing to HAND (including antiretroviral toxicity, substance use, and aging), infection of resident brain cells, and new neuroprotective therapeutics.

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors including physical, cultural, structural, and financial barriers have contributed to HIV late detection. This is the first-of-its-kind study on the regional differences in early detection of HIV within Tajikistan and any country in the Central Asia region. Utilizing Tajikistan Ministry of Health's national HIV data (N=10,700) spanning 2010 to 2023, we developed median regression models with median CD4 cell count as the outcome and as predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old are more likely to be detected early for HIV, whereas those older than 39 years are more prone to late detection. Given their active engagement in age-related and sexual activities, those older than 39 years face a higher risk of HIV transmission to others if diagnosed late. Therefore, they require further attention and targeted interventions. Females are detected earlier compared to their male counterparts, regardless of region of residence. Rural populations are detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. These fluctuations in early detection may signify a shift in attention and resource allocation, potentially affecting efforts to address access gaps during the initial year of the COVID-19 pandemic. There are significant health inequities among different demographic and geographic groups which warrant further attention.

In contrast to some low molar-mass per- and polyfluoroalkyl substances (PFASs), well-established to be toxic, persistent, bioaccumulative and mobile, fluoropolymers (FPs) are water insoluble, safe, bio-inert, durable niche high performance polymers which fulfil the 13 polymer of low concern (PLC) criteria in their recommended conditions of use. In addition, more recent innovations (e.g., the use of non-fluorinated surfactants in aqueous radical (co)polymerization of fluoroalkenes) from industrial manufacturers of FPs are highlighted. This review also aims at showing how these specialty polymers endowed with outstanding properties are essential (even irreplaceable since hydrocarbon polymer alternatives used in similar conditions fail) for our daily life (electronics, Energy, optics, internet of things, transportation, etc) and constitute a special family a part from other “conventional” C1-C10 PFASs found everywhere on the Earth and Oceans. Furthermore, some information reports the recycling (e.g. the unzipping depolymerization of polytetrafluoroethylene, PTFE, into TFE), end of life of FPs, their risk assessment, circular economy and regulations. Various researches are devoted to Environment involving FPs, though they represent a niche volume (with a yearly production of 330,300 tonnes) compared to all plastics (with 460 million tonnes). Complementary to other reviews on PFASs, which lack of such above data, this review presents both fundamental and applied strategies as evidenced by major FP producers.

Background: Community pharmacies have unparalleled potential to increase access to pre-exposure prophylaxis medications (PrEP) for HIV prevention; however, only 17 out of 50 states in the United States have statewide authority for pharmacists to provide PrEP at community pharmacies. Few studies have reported on how pharmacists overcome the legislative barrier and provide PrEP services in restrictive pharmacy prescription states. The objective of this article is to identify the existing primary literature describing pharmacist PrEP service in the community in states with restrictive prescription authority. Methods: A systemic literature review was conducted to identify primary literature that involved community pharmacy service and PrEP conducted in states that do not have expanded pharmacist prescriptive authority between 2000 and 2024. Results: Ten publications were identified describing nine studies, including four interview and survey studies, three intervention reports, and two ongoing clinical trials. None of these studies have a control group. Most pharmacists provide PrEP service in the community through a collaborative practice agreement with a primary care provider. Conclusions: Future clinical studies with randomized controlled designs are required to test novel strategies in the education and implementation of pharmacy-led PrEP services in a community pharmacy setting to increase PrEP access.

The increased life expectancy of PLHIV (People Living with HIV) and the successful highly com-bined antiretroviral therapy (cART) poses new clinical challenges regarding aging and its co-morbid condition. It is commonly believed that HIV infection "accelerates" aging. Human immunodeficiency virus type 1 (HIV-1) infection is characterised by inflammation and immune activation that persists despite cART and that may contribute to the development of co-morbid conditions. Toxicity associated with cART contributes to persistent immune dysregulation. Therefore, we aimed to compare current cART regimens in the light of premature aging to evaluate residual immune activation and inflammation in virologically suppressed patients. We studied a panel of biomarkers (IFN-γ, IL-1β, IL-12p70, IL-2, IL-4, IL-5, IL-6, IL-13, IL-18, GM-CSF, TNF-α, C-reactive protein, D-dimer, soluble CD14), which could provide a non-invasive and af-fordable approach to monitor HIV-related chronic inflammation. The results of the current study do not provide hard evidence favoring a particular cART regimen, although they show less fa-vorable regimen profile containing protease inhibitor. Our data suggests incomplete reduction of inflammation and immune activation in terms of the effective cART. It is likely that the inter-est in various biomarkers related to immune activation and inflammation as predictors of clini-cal outcomes among PLHIV will increase in the future.

Both bacteria product flagellin and macrophages are implicated in HIV infection/disease progression. However, the impact of their interaction on HIV infection and the associated mechanisms remain to be determined. We thus examined the effect of the flagellins on HIV infection of primary human macrophages. We observed that the pretreatment of macrophages with the flagellins from the different bacteria significantly inhibited HIV infection. The mechanistic investigation showed that the flagellin treatment of macrophages downregulated the major HIV entry receptors (CD4 and CCR5) and upregulated the CC chemokines (MIP-1α, MIP-1β, and RANTES), the ligands of CCR5. These effects of the flagellin could be compromised by a toll like receptor 5 (TLR5) antagonist. Given the important role of flagellin as a vaccine adjuvant in TLR5 activation-mediated immune regulation and in HIV infection of macrophages, future investigations are necessary to determine the in vivo impact of flagellin-TLR5 interaction on macrophage-mediated innate immunity against HIV infection and the effectiveness of flagellin adjuvant-based vaccines studies.

Infection with human immunodeficiency virus (HIV) and induced acquired immune deficiency syndrome (AIDS) represent one of the greatest health burdens worldwide. The complex pathophysiological pathways that link highly active antiretroviral therapy (HAART) and HIV infection per se with dyslipidemia make the management of lipid disorders and the subsequent increase in cardiovascular risk essential for the treatment of people living with HIV (PLHIV). Amongst the HAART regimens, darunavir and atazanavir in terms of protease inhibitors, tenofovir disoproxil fumarate, nevirapine or rilpivirine in terms of nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors respectively, and especially integrase inhibitors, have demonstrated the most favorable lipid profile emerging as sustainable options in HAART substitution. To this day, statins remain the cornerstone pharmacotherapy for dyslipidemia in PLHIV, although important drug-drug interactions with different HAART agents should be taken into account upon treatment initiation. For those intolerant or not meeting therapeutic goals, the addition of ezetimibe, PCSK9, bempedoic acid, fibrates or fish oils should also be considered. This review summarizes the current literature on the multifactorial etiology and intricate pathophysiology of hyperlipidemia in PLHIV, with an emphasis on the role of different HAART agents, while also providing valuable insights into potential switching strategies and therapeutic options.

In a single-center, retrospective study, 22 cases were enrolled and divided into two groups: those who underwent surgical wide excision (group A) and those who did not (group B). The study included 13 cases in group A and 9 cases in group B. In group A, 6 cases solely underwent surgical wide excision, while 7 cases received additional treatments like radiotherapy or chemotherapy. Conversely, in group B, 4 cases received chemotherapy, 4 cases received radiotherapy, and 1 case was managed through observation alone. The mean follow-up time was 60.15 months in group A and 43.44 months in group B, with no significant difference observed. In group A, 9 cases resulted in mortality, whereas 6 cases died within the follow-up period in group B. Lesion-free intervals post-operation were observed predominantly in group A, while 7 cases in group B never experienced freedom from skin lesions. Kaplan-Meier survival curve analysis demonstrated a significant difference between the survival curves of the two groups (P = 0.046). Among non-HIV Kaposi’s sarcoma patients, surgical wide excision appears to have a role in treatment. Patients in group A exhibit a more favorable outcome in the survival curve analysis.

There is currently no cure for HIV infection although adherence to effective antiretroviral therapy (ART) suppresses replication of the virus in blood, increases CD4+ T-cell counts, reverses immunodeficiency, and increases life expectancy. Despite these substantial advances, ART is a lifelong treatment for people with HIV (PWH) and upon cessation or interruption, the virus quickly rebounds in plasma and anatomic sites including the central nervous system (CNS), resulting in disease progression. With recent advances in quantifying viral burden, detection of genetically intact viral genomes, and isolation of replication-competent virus from brain tissues of PWH receiving ART, it has become apparent that the CNS viral reservoir (largely comprised of macrophage type cells) poses a substantial challenge for HIV cure strategies. Other obstacles impacting the cure of HIV include ageing populations, substance use, comorbidities, limited antiretroviral drug efficacy in CNS cells and ART-associated neurotoxicity. Herein, we review recent findings including studies of the proviral integration sites, reservoir decay rates, and new treatment/prevention strategies in the context of the CNS, together with highlighting the next steps for investigations of the CNS as a viral reservoir.

Background: The increased vascular risk associated to Varicella- Zoster Virus (VZV) reactivation is extensively established in the general population. This retrospective cohort study investigates whether this observation holds true for People Living With HIV (PLWH), a group already con-fronting heightened cardiovascular risk. Methods: Among PLWH who initiated antiretroviral therapy (ART) at our center and have been under our care for > 24 months since January 1st, 2005, individuals with a history of Herpes Zoster (HZ) were identified and compared their features with those of PLWH with no history of HZ. The prevalence of ischemic events (Deep Venous Thrombosis, Stroke, Acute Myocardial Infarction) was calculated and compared using Chi Square. Odds Ratios (O.R.) with 95% Confidence Intervals (C.I.) for ischemic events following HZ were evaluated through univariate and multivariate logistic regression. Results: Overall, 45/581 PLWH reported HZ. Ischemic events followed HZ significantly more often than the other group (13% vs. 5%, p=0.01). Both positive serology for VZV and HZ correlated with increased ischemic risk (O.R. 4.01, 95% C.I. 1.38-11.6, p=0.01 and O.R. 3.14, 95% C.I. 1.12-7.68, p=0.02, respectively), though pre-existing heart disease demonstrated stronger predictive value in multivariate analysis(O.R. 8.68, 95% C.I. 2.49-29.50, p=0.001). Conclusions: VZV potentially exacerbates vascular risk for PLWH, particularly in the presence of other predisposing factors. Further research is needed to confirm our data.

The human interferon-induced transmembrane (IFITM) proteins inhibit the fusion of a broad spectrum of enveloped viruses, both when expressed in target cells and when present in infected cells. Upon expression in infected cells, IFITMs incorporate into progeny virions and reduce their infectivity by a poorly understood mechanism. Since only a few Env glycoproteins are present on HIV-1 particles, and Env clustering has been proposed to be essential for optimal infectivity, we asked if IFITM protein incorporation modulates HIV-1 Env clustering. The incorporation of two members of the IFITM family, IFITM1 and IFITM3, into HIV-1 pseudoviruses verified by Western blotting correlated with a marked reduction of infectivity. Super-resolution imaging of Env distribution on single HIV-1 pseudoviruses did not reveal significant effects of IFITMs on Env clustering. However, IFITM3 markedly reduced the Env processing and incorporation into virions relative to control and IFITM1-containing viruses. These results suggest that IFITM1 and IFITM3 restrict progeny HIV-1 infectivity via distinct mechanisms. We propose that IFITM1 interferes with viral fusion by altering the properties of the viral membrane or Env functionality by means other than disrupting Env clusters, while IFITM3 also targets Env processing and incorporation into progeny virions.

Intimate partner violence (IPV), particularly sexual and emotional violence, against Black mothers who acquire human immunodeficiency virus (HIV) during childbearing age is a significant health and social concern worldwide requiring targeted interventions and precautions. IPV against women increases the chances of early mixed feeding, putting infants at high risk of mother-to-child transmission of HIV and increased infant morbidities. Although violence complicates many Black mothers’ lives, there is limited research evidence about the critical intersections of violence, HIV, and Black motherhood. Women's fears associated with IPV make them less likely to disclose their positive HIV status to their partners which subsequently prevents them from using the recommended guidelines for safe infant feeding practices. This review aims to explore the critical intersections between IPV and HIV and the impact of both on the infant feeding practices of Black mothers living with HIV. Furthermore, the theme of IPV and how it overlaps with other factors such as HIV-positive status and gender dynamics to compromise the Black motherhood experience are the focus of this narrative review of existing literature. Understanding the intersection of IPV and other factors influencing infant feeding practices among women living with HIV will help inform programming and policy interventions for HIV-positive Black mothers who may be experiencing IPV during the perinatal period.

Aims: The aims of this meta-analysis were to assess: the prevalence of Post-Acute COVID-19 sequalae in HIV positive patients; average time of diagnosis; and meta-regress for possible moderators of PACS.Methods: A standard search strategy was used in PubMed, and then later modified according to each specific database to get the best relevant results. These included Medline indexed journals; PubMed Central; NCBI Bookshelf and publishers' Web sites in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Search terms included “long COVID-19 or post-acute COVID-19 syndrome/sequalae”, “persons living with HIV or HIV. The criteria for inclusion were published clinical articles reporting HIV in association with long COVID-19, further, the average time to an event of post-acute COVID-19 sequelae among primary infected patients with COVID-19. Random-effects model was used. Rank Correlation and Egger's tests were used to ascertain publication bias. Sub-group, sensitivity and meta-regression analysis were conducted. A 95% confidence intervals were presented and a p-value < 0.05 was considered statistically significant. Review Manager 5.4 and comprehensive meta-analysis version 4 (CMA V4) were used for the analysis. The review/trial was PROSPERO registered (CRD42022328509).Results: A total of 43 studies reported post-acute COVID-19 syndrome. Of those, five reported post-acute COVID-19 sequalae in PLHIV. Prevalence of post-acute COVID-19 sequalae was 43.1% (95% CI 20.5% to 68.9%) in persons living with HIV (PLWH). The average time to PACS diagnosis was 4 months at 64% [0.64 (95% CI 0.230, 0.913) (P < 0.0000), I²= 93%] and at one year to PACS diagnosis was at 70 %, however with non-significant correlation (P > 0.05). On comorbidities, asthenia was associated with PACS at 17.6 % [0.176 (95% CI 0.067, 0.385) (P = 0.008), I²= 86%] while fatigue at 82%, however not related with PACS event incidence (P < 0.05). Americas, Asian and European regions showed PACS events rates of 82%, 43% and 19 % respectively (P<0.05) relative to HIV infection. Conclusion: PACS prevalence in PLWH was 43% occurring at an average time of 4 months at 64% and 70 % at 12 months however non-significant with PACS. Asthenia was significantly associated with PACS at 17.6 % while fatigue at 82%, however not related with PACS event incidence. Americas recorded the highest PACS event rates in PLWH.

: Background and objectives: One of the most severe symptoms of extrapulmonary tuberculosis (TBEP) is tuberculous meningitis (TBM) which is linked to significant morbidity and high mortality. It is well recognized that HIV-positive people are more likely to develop TBEP, including TBM, especially if they have severe immunodeficiencies. Material and methods: We conducted a retrospective clinical study based on hospital medical records of the diagnosed patients with HIV/AIDS and Tuberculous Meningitis in North-eastern Romania, hospitalized at "Sf. Parascheva" Clinical Hospital of Infectious Diseases from Iasi. We aim to highlight the profile and the caracteristics of the HIV/AIDS and Tuberculous Meningitis coinfection cases. The time frame under study was from January 1st, 2010, to December 1st, 2022. Results: Our Center has a total number of patients on record of 1692. Patients co-infected with HIV- TB were 195 of which 19 cases were HIV- TBM coinfection and it was more common in women. From this total, 6 cases were late presenters and 13 patients were already in the center's records with a deficient immunological viral status, non-compliant, and non-adherent to antiretroviral therapy. The average age in the study group was 27 years old. The mean admission day number was 17.73 days. CSF findings (qualitative and quantitaitve examination, biochemestry) were in accordance with the literature. Conclusions: The key to the management of the HIV-positive patient is the multidisciplinary approach and access to antiretroviral therapy. We must find and eliminate obstacles affecting patients and the healthcare system. In order to increase ART uptake among HIV-infected TB patients and to put an end to the TB and HIV epidemics.

Cryptococcosis is a leading cause of death among people with HIV in sub-Saharan Africa. Limited diagnostic and therapeutic options significantly impair treatment options in Africa. We investigated the burden of cryptococcosis and related mortality among people with HIV and suspected sepsis in Ethiopia. We conducted a prospective cohort at 1) Adama Hospital Medical College and 2) Asella Referral and Teaching Hospital from September 2019 to November 2020. We enrolled adult HIV-infected patients presenting with suspected sepsis and assessed 28-day survival. We performed blood cultures and cryptococcal antigen (CrAg) testing. In total, 82 participants were enrolled with a median age of 35 years and 61% being female. Overall, 11(13%) had positive CrAg tests, of which 5 had Cryptococcus detected in blood cultures. Despite high-dose fluconazole (1200mg/d) monotherapy in patients with positive CrAg tests, the 28-day mortality was 64%(7/11), being significantly higher than in CrAg-negative patients (9%(6/71); p&lt;0.001). Cryptococcosis is the leading cause of mortality among HIV-infected sepsis patients. CrAg screening in HIV-infected patients attending emergency department can minimize the cryptococcosis missing case irrespective of CD4 count and viral load. These findings warrant the need of a bundle approach for diagnosis of HIV-infected persons presenting with sepsis in low- and middle-income countries.

There is a significant overlap between HIV infection and substance use disorders. Dopamine (DA) is the most abundantly upregulated neurotransmitter in Methamphetamine abuse, with receptors (DRD1-5) that are expressed by neurons as well as by a large diversity of cell types, including innate immune cells that are targets of HIV infection, making them responsive to the hyperdopaminergic environment that is characteristic of stimulant drugs. Therefore, the presence of high levels of dopamine may affect the pathogenesis of HIV, particularly in the brain. The stimulation of HIV-latently infected U1 promonocytes with DA significantly increased viral p24 levels in the supernatant at 24 hrs, suggesting effects on activation and replication. Using selective agonists to different DRDs, we found that DRD1 played a major role in activating viral transcription, followed by DRD4, which increased p24 with a slower kinetic. Transcriptome and systems biology analyses led to the identification of a cluster of genes responsive to DA, where S100A8 and S100A9 were most significantly correlated with the early increase of p24 levels following DA stimulation. Conversely, DA increased the expression of these genes’ transcripts at the protein level, respectively MRP8 and MRP14, which form a complex also known as Calprotectin. Interestingly, MRP8/14 was able to stimulate HIV transcription in latent U1 cells, and this occurred via binding to the receptor for advanced glycosylation end-product (RAGE). Using selective agonists, both DRD1 and DRD4 increased MRP8/14 on the surface and in the cytoplasm, as well as secreted in the supernatants. On the other hand, while DRD1/5 did not affect the expression of RAGE, DRD4 stimulation caused its downregulation, offering a mechanistic for the delayed effect via DRD4 on p24 increase. To cross-validate MRP8/14 as a DA signature with biomarker value, we tested its expression in HIV+ Meth users’ brains and peripheral cells. MRP8/14+ cells were more frequently identified in mesolimbic areas such as basal ganglia of HIV+ Meth+ cases compared to HIV+ non-Meth users or to controls. Likewise, MRP8/14+ CD11b+ monocytes were more frequent in HIV+ Meth users, particularly in participants with detectable viral load in the CSF. Overall, our results suggest that the MRP8 and MRP14 complex may serve as a signature to distinguish subjects using addictive substances in the context of HIV, and that this may play a role in aggravating HIV pathology by promoting viral replication in people with HIV who use Meth.

The Centers for Disease Control and Prevention recommends everyone between 13-64 years be tested for HIV at least once as a routine procedure. HIV routine screening is reimbursable by Medicare, Medicaid, expanded Medicaid, and most commercial insurance plans. Yet, scaling-up HIV routine screening remains a challenge. We conducted a scoping review for studies on financial benefits and barriers associated with HIV screening in clinical settings in the U.S. to inform an evidence-based strategy to scale-up HIV routine screening. We searched Ovid MEDLINE®, Cochrane, and Scopus for studies published between 2006 - 2020 in English. The search identified 383 Citations; we screened 220 and excluded 163 (outside the time limit, irrelevant, or outside the U.S.). Of the 220 screened articles, we included 35 and disqualified 155 (did not meet the eligibility criteria). We organized eligible articles under two themes: financial benefits/barriers in healthcare settings (9 articles); and Cost-effectiveness in healthcare settings (26 articles). The review concluded recommendations in three areas: (1) Finance: Incentivize healthcare providers/systems for implementing HIV routine screening and/or separate its reimbursement from bundle payments; (2) Personnel: Encourage nurse-initiated HIV screening programs in primary care settings and educate providers on CDC recommendations; and (3) Approach: Use opt-out approach.

PrEP uptake in the Netherlands is growing but remains at suboptimal levels. Hence, the analysis of hurdles is paramount. Given the initial focus of PrEP provision among men-who-have-sex-with-men (MSM) via a demonstration project that was launched in June 2015, AmPrEP in Amsterdam, and pharmacies in the main urban areas (so called “Randstad”, entailing Amsterdam, Utrecht, Leiden, The Hague and Rotterdam), investigating regional differences is necessary. This study seeks to unravel regional differences jointly with psycho-social determinants of PrEP uptake. This cross-sectional study included 3,232 HIV-negative Dutch MSM recruited via the EMIS survey in late 2017. Prevalence and standardized prevalence ratio (SPR) of PrEP awareness, intention and uptake were measured on a regional level (Randstad vs. the rest of the country). Multilevel logistic modelling was conducted to identify the association of PrEP uptake with PrEP awareness and intention, sociodemographic, psycho-social determinants, and random effects from regional differences. MSM from the Randstad used more PrEP (SPR=1.4 vs. 0.7) compared to the rest of the country, but there were minor differences for awareness and intention. The regional distinction was estimated to explain 4.6% of the PrEP use variance. We observed a greater influence from PrEP intention (OR=4.5, 95%CI 2.0-10.1), while there was limited influence from the awareness of PrEP (OR=0.4, 95%CI 0.04-4.4). Lower education (OR=0.4, 95%CI 0.2-0.9) was negatively associated with PrEP uptake, however, no significant difference was found between middle and high education (OR=1.2, 95%CI 0.7-2.0). We showed that regional differences – MSM in non-urban regions – and other psycho-social determinants account for lower PrEP uptake. Based on these findings, more fine-tuned PrEP access with a focus on non-urban regions can be implemented, and tailored campaigns increasing intention/use can be conducted among target populations.

Background: Vertical transmission of HIV infection can occur during pregnancy, during childbirth or through breastfeeding. The recommendations issued by the various international guidelines (WHO 2010, EACS 2017, DHHS 2017) on the safety of breastfeeding of HIV-infected women in effective antiretroviral treatment do not provide univocal indications referring to individual countries the choice to advise or advise against such procedure. Methods: A retrospective study was conducted in a small cohort of HIV-infected pregnant women who, despite the information received, decided to breastfeed their children. The observation was carried out in the period between March 2017 and June 2021. In all newborns, prophylaxis therapy was initiated at birth, according to the treatment guidelines, the scheme adopted involved the administration of zidovudine (AZT) orally for 4 weeks, started immediately after the childbirth. Breastfeeding time was, on average, 5 months. Results: No contagion was diagnosed. All infants were tested for HIV-RNA at birth, 1, 3, and 6 months after birth, and 1, 3 and 3 months after stopping breastfeeding. Conclusions: The data obtained represent, in our opinion, a solicitation to discuss and re-evaluate scientific evidence that starting from "Undetectable Equals Untransmittable" (U = U) can open a scientific and cultural review of breastfeeding.

A mathematical model, composed of two non-linear differential equations that describe the population dynamics of CD4 T cells in the human immune system, as well as viral HIV particles, is proposed. The invariance region is determined, classical equilibria stability analysis is performed using the basic reproduction number, and numerical simulations are carried out, in order to illustrate stability results. Later, the model is modified with a delay term, which describes the time that cells require for immunological activation. This generates a two-dimensional integro-differential system, which is transformed into a system with three ordinary differential equations, via auxiliary variable use. For the new model, equilibrium points are determined, their local stability is examined, and results are studied by way of numerical simulation.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, has been declared by the World Health Organization (WHO) as a pandemic. Unfortunately, finding a vaccine or developing drugs from the scratch is a time-consuming luxury given the widespread and high fatality rates of the virus. In the short term, repurposing of drugs already in use seem to be the most rational step to quickly and effectively curb the virus. Several antiviral agents had been proposed as possible remedies, but the 4-aminoquinolines, Chloroquine (CHQ) and hydroxychloroquine (HCHQ) appear to be generating more interest. They are generic, cheaply available and have proven efficacy against malaria parasites in Africa. The human immunodeficiency virus (HIV), on the other hand, targets the immune system thereby reducing the patient’s ability to fight infections. Sadly, 68% of the global HIV burden occur in Africa. It is therefore anticipated that incidence of severe forms of COVID-19 could occur in Africa because of associated endemic conditions that compromise the immune system. With CHQ and HCHQ being considered for clinical use against COVID-19, there is a need to highlight their potential merits and confounding variables in the subgroup of patients with or without HIV.

Background: Trichomoniasis is the most common non-viral STI globally and yet is not a reportable disease. Trichomonas Vaginalis is an important source of reproductive morbidity and may increase risk of acquisition and transmission of HIV. WHO and CDC recommend various regimens of Nitro-Imidazoles for treatment. The common Nitro-Imidazoles used for Trichomoniasis are Metronidazole and Tinidazole, which vary in their cost, efficacy and side effect profile and it is relevant to study these factors, for better management of the patients. Objectives: This study aims to compare and study the efficacy, compliance of various treatment regimens, their outcomes and side-effects for Trichomoniasis, among STI clinic attendees in Trinidad. Methods: A clinical trial study was designed and after obtaining the informed consent a routine clinical examination was conducted and the swabs for Trichomoniasis tests were collected for diagnosis from the 692 participants. Out of 692 participants, Eighty two (82) patients with established diagnosis of Trichomonas infection were quasi-randomly treated using different regimens. Compliance to treatment, side effects and outcome were evaluated. Results: The prevalence of the Trichomoniasis in population attending our STI clinic is 11.9% and prevalence of HIV is 9%. Of the total 82 participants for the treatment, 80% were females; nearly 90% of the patients belonged to age group 15-45 years and over 60% were below 30 yrs. Among those diagnosed for Trichomonas vaginalis, 13.3% had associated HIV infection. The compliance with respect to single dose treatment was significantly better than the long duration oral regimen and has significant relation with side effects of the treatment. The outcome is generally better and comparable and shows no significant difference between different treatment regimens used in the study. Conclusions: Metronidazole and Tinidazole are commonly used drugs in various regimens. compliance is better with those treated with Tinidazole and Metronidazole stat, than with other groups. Outcome is comparable between these regimens, especially when combined with other important factors like abstinence and treatment of the partners. The treatment regimens mainly differ in the compliance and side effects profile, which suggests that to improve the compliance the drugs with less side effects, short course regimen would be a preferred choice.

HIV-1 assembly is a complex mechanism taking place at the plasma membrane of the host cell. It requires nice spatial and temporal coordination to end up with a full immature virus. Researchers have extensively studied HIV-1 assembly molecular mechanism during the past decades, in order to dissect the respective roles of viral proteins, viral genome and host cell factors. Nevertheless, the time course of the process has been observed in living cells only a decade ago. The very recent revolution of optical microscopy, combining high speed and high spatial resolution now permit to study assemblies and their consequences at the single molecule level within (living) cells. In this review, after a short description of these new approaches, we will show how HIV-1 assembly in cells has been revisited using these advanced super resolution microscopy techniques and how much it could make a bridge in studying assembly from the single molecule to the host cell.

Microbiota plays a key role in various body’s functions, physiological, metabolic and immunological processes, through different mechanisms such as the regulation of the development and/or functions of different types of immune cells in the intestines. Several evidences indicate that alteration in the gut microbiota can influence infectious and non-infectious diseases. Bacteria that resides on the mucosal surface or within the mucus layer participate in interactions with the host immune system, and a healthy gut microbiota is essential for the development of mucosal immunity. The immunomodulatory activity of probiotics has been proposed in several bowel disorders or in aging-related dysfunctions. In HIV infected patients, the intestinal immune system is affected and inflammation persists during ART therapy too. Several studies are in progress to investigate the ability of probiotics to modulate epithelial barrier functions, microbiota composition and microbial translocation in HIV infection. This mini-review aims to suggest how the use of probiotics is beneficial not only in maintaining a healthy status but also to improve conditions in HIV subjects.

Background/objective: A retrospective study was conducted to access better understanding of the prevalence and risk factors of OIs in HIV-positive individuals, informing targeted interventions and enhancing overall health outcomes. Methods: Medical records 212 of patients (61.79% female, 38.21% male) were accessed to extract relevant information for the study. Fisher’s exact test revealed significant associations between gender, substance abuse, healthy diet practices, and having single or multiple partners with the development of opportunistic infections.Results: A total of 212 HIV-positive patients were enrolled, with a majority being female (61.79%) and adults aged between 25 and 65 years (68.87%). Most participants were single (83.02%), unemployed (66.9%), and had a history of substance abuse (61.79%). The prevalence of opportunistic infections was 15.09%, with pulmonary tuberculosis being the most common (75%), followed by extrapulmonary tuberculosis (18.75%) and herpes zoster (6.25%). Females were less likely to develop opportunistic infections compared to males (OR=0.26; 95% CI: 0.12 to 0.57; p=0.0007). Patients not using substances were less likely to develop opportunistic infections (OR=0.32; 95% CI: 0.13 to 0.82; p=0.0170). Those with unhealthy diet practices were significantly more likely to develop opportunistic infections (OR=8.46; 95% CI: 3.56 to 20.53; p<0.0001). Patients with multiple partners were more likely to develop opportunistic infections (OR=3.33; 95% CI: 1.27 to 9.26; p=0.0250). Conclusion: These findings highlight the importance of addressing these factors in the management of HIV-positive patients to reduce the risk of opportunistic infections.

Next-generation sequencing(NGS) for HIV drug resistance(DR) testing has an increasing number of applications for detection of Low-abundance drug resistant variants(LA-DRVs) as its features of quasispecies. However there is less information on detection performance in DR detection with NGS.To determine the feasibility of NGS technology in LA-DRVs detection for HIV-1 pre-treated patients.In this study,80 pre-treated patients’ samples accepted both NGS and Sanger sequencing(SS) in HIV-1 drug resistance testing. The results show that NGS presents higher sensitivity in mutation sites discovery at 5% threshold. NGS shows a satisfactory consistency comparing with SS in both protease inhibitors(PIs) and Integrase inhibitor(INSTIs), more than 90%. But worse consistency in Nucleotide reverse transcriptase inhibitors(NRTIs), only ranging from 61.25%-87.50%. The consistency of Non-nucleotide reverse transcriptase inhibitors(NNRTIs) between NGS and SS was around 85%. NGS shows the highest sensitivity of 91.3% at 5% threshold. The application of NGS technology in HIV-1 genotype resistance detection in different populations infected with HIV needs more documents and to be confirm further.

This study aims to comprehensively understand the provision of skincare solutions for individuals living with HIV, focusing on the efficacy of existing treatments, challenges in accessing dermatological care, and the preferences of individuals living with HIV for personalized skincare solutions. The study triangulated data from structured surveys and in-depth interviews with a purposive sample of individuals living with HIV, healthcare professionals, and experts in public health and social work, using a mixed-methods approach. The structured surveys provided specific data points, while the in-depth interviews and participant observations yielded rich, contextual insights. The results revealed a need for more personalized skincare solutions for individuals living with HIV, challenges in accessing dermatological care, and concerns regarding the efficacy of existing treatments. The integrated analysis of quantitative and qualitative data provided a nuanced understanding of the factors influencing skincare solutions for this population. Conclusions drawn from the study emphasize the importance of tailored skincare interventions, improved access to dermatological care, and the need for collaborative efforts between healthcare providers and individuals living with HIV. Future research directions include longitudinal studies to assess the long-term effectiveness of personalized skincare solutions and the exploration of innovative interventions integrating dermatological care and social support for individuals living with HIV.

Background: Diabetic foot sepsis (DFS) accounts for approximately 60% of hospital admissions in patients with diabetes mellitus (DM). Individuals with DM are at risk of severe COVID-19. This study investigated investigated factors associated with major amputation and mortality in patients admitted with DFS during the COVID-19 pandemic. Methods: Demographic information, COVID-19 and HIV status, clinical findings, laboratory results, treatment and outcome from records of patients with diabetic foot sepsis. The chi-square test, Fisher’s test, Student t-test or Mann-Whitney compare findings when appropriate. Multivariate logistic regression to determine factors that were associated with major amputation and mortality. Results of logistic regression were compared with outputs from analysis using machine learning algorithms. Kaplan-Meier survival curve to compare survival between COVID-19 positive and negative patients. Statistical was a p-value below 0.05. Supervised machine learning algorithms were used to compare their ability to predict major and deaths. Results: Overall, 114 records were found and 57.9% (66/114) were of male patients. The mean age of the patients was 55.7 (14) years and 47.4% (54/114) and 36% (41/114) tested positive for COVID-19 and HIV, respectively. The median c-reactive protein was 168mg/dl, urea 7.8mmol/l and creatinine 92µmol/l. The mean potassium level was 4.8±0.9mmol, and glycosylated haemoglobin 11.2±3%. The main outcomes included major amputation in 69.3% (79/114) and mortality of 37.7% (43/114) died. AI. The level of potassium, urea, creatinine and HbA1c were significantly higher in the deceased. Conclusions: The COVID-19 pandemic led to an increase in the rate of major amputation and mortality in patients with DFS. The in-hospital mortality was higher in patients above 60 years of age who tested positive for COVID-19. The Random Forest algorithm of ML can be highly effective predicting major amputation and death in patients with DFS.

HIV-associated cardiovascular diseases remain a leading cause of death in people living with HIV/AIDS (PLWHA). Although antiretroviral drugs suppress the viral load, they fail to remove the virus entirely. HIV-1 Nef protein is known to play a role in viral virulence and HIV latency. Expression of Nef protein can be detected in different organs, including cardiac tissue. Despite the established role of Nef protein in HIV-1 replication, its impact on organ function inside the human body is not clear. To understand the effect of Nef at the organ level, we created a new Nef transgenic (Nef-TG) mouse that expresses Nef protein in the heart. Our study found that Nef expression caused inhibition of cardiac function and pathological changes in the heart with increased fibrosis, leading to heart failure and early mortality. Further, we found that cellular autophagy is significantly inhibited in cardiac tissue of Nef-TG mice. Mechanistically, we found that Nef protein causes the accumulation of Bcl2 and Beclin-1 protein in the tissue, which may affect the cellular autophagy system. Additionally, we found Nef expression causes upregulation of cellular senescence marker p21, and senescence-associated -galactosidase expression. Our findings suggested that Nef-mediated inhibition of autophagy and induction of senescence markers may promote aging in the PLWHA. Our mouse model could help us to understand the effect of Nef protein on organ function during latent HIV infection.

The ribonuclease H (RNase H) active site of HIV-1 reverse transcriptase (RT) is the only viral enzyme not targeted by approved antiretroviral drugs. Using a fluorescence-based in vitro assay, we screened 65,239 compounds at a final concentration of 10 µM to identify inhibitors of RT RNase H activity. We identified 41 compounds that exhibited 50% inhibitory concentration (i.e., IC50) values &lt; 1.0 µM. Two of these compounds, 2-(4-methyl-3-(piperidin-1-ylsulfonyl)phenyl)benzo[d]isothiazol-3(2H)-one (1) and ethyl 2-(2-(3-oxobenzo[d]isothiazol-2(3H)-yl)thiazol-4-yl)acetate (2), which both share the same benzisothiazolone pharmacophore, demonstrate robust antiviral activity (50% effective concentrations of 1.68 ± 0.94 µM and 2.68 ± 0.54, respectively) in the absence of cellular toxicity. A limited structure-activity relationship analysis identified two additional benzisothiazolone analogs, 2-methylbenzo[d]isothiazol-3(2H)-one (3) and N,N-diethyl-3-(3-oxobenzo[d]isothiazol-2(3H)-yl)benzenesulfonamide (4), which also resulted in inhibition of RT RNase H activity and virus replication. Compounds 1, 2 and 4, but not 3, inhibited the DNA polymerase activity of RT (IC50 values ~ 1 to 6 µM). In conclusion, benzisothiazolone derivatives represent a new class of multifunctional RT inhibitors that warrants further assessment for the treatment of HIV-1 infection.

M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in the setting of non-suppressive antiretroviral therapy (ART) and accumulates in the HIV reservoir. There were continuous efforts to evaluate the impact of M184V mutation on the treatment outcomes in people with HIV (PWH). Since lamivudine remains an extensively used part of recommended antiretroviral combinations, M184V is commonly detected in patients with virological failure. ART guidelines do not recommend the use of drugs impacted by resistance-associated mutations as they have been confirmed to comprise a risk factor for virological failure. However, previous authors suggest that 3TC/FTC can remain active even in the presence of M184V. Obtaining the viral resistance profile for each individual both treated or ART-naïve is a key challenge for lifelong treatment management.Given the potential benefits of lamivudine in the ART combinations, the investigation of M184V remains of high interest for clinicians and researchers. This is a review of literature for the challenges in treating both naïve and experienced individuals carrying the M184V resistance mutation, including virological failure, virological suppression, and resistance to ART.

Two decades after the antiretroviral therapy (ART) introduction, several challenges still prevail in maintaining people living with HIV (PLHIV), even with "Test and Treat" and/or "Rapid Start of ART" initiatives, as well as the scale-up of ART worldwide to promote access and adherence to treatment. This review examined articles on ART adherence in Africa between 2016 and 2023, published in English and indexed in PubMed. A total of 16 articles out of 2415 were eligible and included for analyses. Overall, ART adherence rates in SSA regions ranged from 43% to 84%. Rates in the centre of the SSA region ranged from 58% to 80%, in the north from 50% to 83%, in the south from 77% to 84%, in the west from 43% to 60% and in the east from 69% to 73%. Most African countries use the self-report to assess treatment adherence, although unreliable. The main factors with negative influence on ART adherence were comorbidities, lack of motivation, socioeconomic difficulties or side effects. Conclusion: Adherence to ART is a good indicator for controlling the spread of HIV. It is important to overcome the barriers that make it difficult to comply with ART and reinforce the factors that facilitate the accession of medication.

(1) Background: Hepatitis B virus (HBV) viral load (VL) is useful in determining treatment eligibility, however, due to high costs associated with the test, hepatitis B e antigen (HBeAg) is recommended as a proxy for HBV VL in resource-limited settings. (2) Methods: We used 299 archived plasma samples with hepatitis B surface antigen (HBsAg), HBeAg, and HBV VL (cut-off of 20,000 IU/mL and 200,000 IU/mL) results from people living with human immunodeficiency virus (PLWH). HBeAg and HBV VL results were analyzed to evaluate the use of HBeAg to determine CHB treatment eligibility and qualification of HBV prevention of mother-to-child transmission (PMTCT) prophylaxis for the first time in Botswana. (3) Results: Approximately 70.8% and 87.5% of participants with HBeAg-positive serology had HBV viral loads ≥20,000 IU/mL and 200,000 IU/mL respectively. Using logistic regression, the odds of having a qualifying HBV VL for CHB treatment and PMTCT prophylaxis were respectively 55.5 and 110.4 times higher in participants with positive HBeAg serology indicating a statistically significant association between HBeAg status and HBV VL. (4) Conclusions: HBeAg detection may not always correlate with high HBV VL, warranting further research focusing on this association, and other biomarkers that correlate better with HBV VL.

The metabolome is the composition of all molecules present in an organism, metabolomics science allows us to qualitatively and quantitatively analyze metabolites and understand the biochemical state in response to genetic and environmental changes. The purpose of the study was to identify the metabolomic profile of biofluids (saliva and urine) of patients living with HIV/AIDS (PLHIV/AIDS), and establish a possible association of metabolites with periodontal disease (PD). It was an analytical and descriptive study composed of 65 patients seen at the Center for Studies and Care for Special Patients (CEAPE-UNIP), who were divided into 4 predetermined groups (G), G1-PLHIV/AIDS and without PD, G2- PLHIV/Aids and with PD, G3-people without HIV/Aids and without PD, G4-people without HIV/Aids and with PD. The results showed that in relation to urine, G2 has the highest mean area of concentration of metabolites. There are statistically significant differences between G1 and G2. The area of G2 is greater than G3, and greater than G4. There are no differences between G3 and G4, neither between G1 and G3, nor between G1 and G4. Regarding saliva, there are no statistically significant differences when comparing the groups for the mean areas of concentration of metabolites. We conclude that it was possible to distinguish the metabolic profile of PLHIV/Aids with periodontal disease and without periodontal disease, some metabolites are over expressed in PLHIV/Aids and with PD. Most of the metabolites of the carbohydrate group are under expressed in PLHIV/AIDS, even in systemic compensation situations these patients presented a different metabolic profile.

Due to a common mode of transmission through infected human blood, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection is relatively prevalent. In alignment with this, HCV co-infection is associated with an increased size of the HIV reservoir in highly active antiretroviral therapy (HAART)-treated individuals. Hence, it is crucial to comprehend the physiological mechanisms governing the latency and reactivation of HIV in reservoirs. Consequently, our study delves into the interplay between HCV/HIV coinfection in liver cells and its impact on the modulation of HIV latency. We utilized the latently infected monocytic cell line (U1) and the latently infected T cell line (J-Lat) and found that mediators produced by the infection of hepatic stellate cells and hepatocytes with HIV and HCV, respectively, were incapable of inducing latency reversal under the studied conditions. This may favor the maintenance of the HIV reservoir size among latently infected mononuclear cells in the liver. Further investigations are essential to elucidate the role of the interaction between liver cells in regulating HIV latency and/or reactivation, providing a physiologically relevant model for comprehending reservoir microenvironments in vivo.

Summary— Introduction: HIV (human immunodeficiency virus) is a virus that attacks and destroys one type of white blood cell, in particular, the CD4 lymphocytes, which are responsible for the body's immune response. This weakens the immune system to such an extent that it can no longer fight other viruses, bacteria, protozoa, fungi, and tumors. Methods: We investigated the potential biological role of the natural compound Polydatin (or piceid) using SwissDock, a web service to predict the molecular interactions that can occur between a target protein and a small molecule. Discussion: For the first time, we have investigated the role of polydatin against HIV-1 protease and HIV-2 protease through a computational approach by comparing their estimated ΔG values (kcal/mol) and the nature of the interactions between the residues in the catalytic center of the HIV proteases.Conclusion: From these simulations, Polydatin has excellent physical properties and an excellent estimated ΔG value (kcal/mol) of about -9.9 kcal/mol against HIV-2 protease and ΔG value (kcal/mol) of about -9.5 kcal/mol against HIV-1 protease. In addition, Polydatin was able to bind to two key amino acids of the catalytic triad sequence common to asparagine proteases (Asp25 and Gly27)

HIV diagnosis and poor HIV management have various detrimental impacts on the lives of people living with HIV (PLHIV). As part of a large qualitative study investigating HIV risk factors and impacts, with the suicide topic not being a focus, this paper describes factors contributing to suicidal ideation and attempts that arose naturally in the stories of women living with HIV (WLHIV) in Yogyakarta and Belu districts, Indonesia. The participants were recruited using the snowball sampling technique. Guided by a qualitative data analysis framework, the data were thematically analysed. Findings indicated participants experienced immense psychological challenges due to the infection, spousal transmission, fear of mother-to-child transmission, and losing a child due to AIDS, which triggered suicidal ideation and attempts. The women’s lack of awareness of HIV management strategies resulted in them feeling trapped and overwhelmed. Associated negative thoughts and the anticipation and experience of stigma relating to their HIV status were influencing factors for thoughts of suicide among participants. Lack of social support from family and friends during the early stage of HIV diagnosis, compounded with pre-existing financial difficulties, lack of income, unemployment, and feeling overburdened, also triggered the women’s thoughts of suicide. Other influencing factors for suicidal ideation and attempts among the women were family breakdown following HIV diagnosis and this was reflected in family disputes, husband-wife separation or divorce, mother-child separation by other family members, reported concern about future relationships, and fear of being rejected or abandoned by their partner due to their HIV positive status. The findings indicate the need for a nuanced approach to counselling within HIV care interventions for couples to support the acceptance of each other’s HIV status whilst maintaining psychological wellbeing. Additionally, the findings indicate the importance of HIV education and awareness among community members for the de-stigmatisation of HIV and to increase the acceptance of PLHIV within families and communities.

Despite intensive HIV education and prevention efforts in the past years, stigmatizing attitudes toward people living with HIV (PLWH) remain a major barrier to HIV prevention and treatment efforts in Vietnam. The purpose of this study was to examine the prevalence of stigmatizing attitudes regarding HIV and identifying correlative factors that impact perceptions of PLWH among women migrant workers working in the industrial zones (IZ) in Hanoi, Vietnam. A cross-sectional study was conducted among 1061 women migrant workers aged 18 to 29 from January to November 2020 in Hanoi, Vietnam. Stigmatizing attitudes toward PLWH were measured using a four-item scale. Multiple logistic regression was conducted to examine factors associated with stigmatizing attitudes. Over seventy-six (76.2 %) of the participants reported having at least one of the four stigmatizing attitudes. Greater levels of stigmatizing attitudes toward PLH were significantly associated with lower HIV knowledge, lower education and being Kinh (the ethnic majority in Vietnam). A high level of stigmatizing attitudes toward PWH among the study participants suggests that there is an urgent need for the development of appropriate culturally interventions and outreach education activities to reduce stigmatizing attitudes toward PWH among women migrant workers working in the IZs in Vietnam.Despite intensive HIV education and prevention efforts in the past years, stigmatizing attitudes toward people living with HIV (PLWH) remain a major barrier to HIV prevention and treatment efforts in Vietnam. The purpose of this study was to examine the prevalence of stigmatizing attitudes regarding HIV and identifying correlative factors that impact perceptions of PLWH among women migrant workers working in the industrial zones (IZ) in Hanoi, Vietnam. A cross-sectional study was conducted among 1061 women migrant workers aged 18 to 29 from January to November 2020 in Hanoi, Vietnam. Stigmatizing attitudes toward PLWH were measured using a four-item scale. Multiple logistic regression was conducted to examine factors associated with stigmatizing attitudes. Over seventy-six (76.2 %) of the participants reported having at least one of the four stigmatizing attitudes. Greater levels of stigmatizing attitudes toward PLH were significantly associated with lower HIV knowledge, lower education and being Kinh (the ethnic majority in Vietnam). A high level of stigmatizing attitudes toward PWH among the study participants suggests that there is an urgent need for the development of appropriate culturally interventions and outreach education activities to reduce stigmatizing attitudes toward PWH among women migrant workers working in the IZs in Vietnam.

In addition to CD4+ T lymphocytes, myeloid cells, and, particularly, differentiated macrophages, are targets of the human immunodeficiency virus type-1 (HIV-1) infection via interaction of gp120Env with CD4 and CCR5 or CXCR4. Both T cells and macrophages support virus replication although with substantial differences. In contrast to activated CD4+ T lymphocytes, HIV-1 replication in macrophages occurs in nondividing cells and it is characterized by virtual absence of cytopathicity both in vitro and in vivo. These general features should be considered in evaluating the role of cell-associated restriction factors aiming at preventing of curtailing virus replication in macrophages and T cells particularly in the context of designing strategies to tackle the viral reservoir in infected individuals receiving combination antiretroviral therapy. In this regard, we will here also discuss a model of reversible HIV-1 latency in primary human macrophages and the role of host factor determining restriction or reactivation of virus replication in myeloid cells.

Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. In this respect the identification of single agents with multitarget potential might represent the ideal solution. Accordingly, a small library of biphenylhydrazo 4-arylthiazoles derivatives has been synthesised and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity.

The outbreak of novel coronavirus (COVID-19) infections in 2019 is in dire need of finding potential therapeutic agents. In this study, we used molecular docking to repurpose HIV protease inhibitors and nucleoside analogues for COVID-19, with evaluations based on docking scores calculated by AutoDock Vina and RosettaCommons. Our results suggest that Indinavir and Remdesivir possess the best docking scores, and comparison of the docking sites of the two drugs reveal a near perfect dock in the overlapping region of the protein pockets. After further investigation of the functional regions inferred from the proteins of SARS coronavirus, we discovered that Indinavir does not dock on any active sites of the protease, which may give rise to concern in regards to the efficacy of Indinavir. On the other hand, the docking site of Remdesivir is not compatible with any known functional regions, including template binding motifs, polymerization motifs and nucleoside triphosphate (NTP) binding motifs. However, when we tested the active form (CHEMBL2016761) of Remdesivir, the docking site revealed a perfect dock in the overlapping region of the NTP binding motif. This result suggests that Remdesivir could be a potential therapeutic agent. Clinical trials still must be done in order to confirm the curative effect of these drugs.

Background: Delhi State AIDS Control Society (DSACS) addressed critical integration of services for Orphan and Vulnerable Children (OVC) in context of HIV. They bridged the policy and implementation divide by formulating a multisectoral-strategy in April 2012, creating a model of "Continuum-of-Care for People-Living with HIV (PLHIV), OVC & Children-Affected-by-HIV (ChABH)” in Delhi. With input from the National Commission for Protection of Child Rights, DSACS sensitized political and administrative machinery about needs and challenges related to HIV/AIDS. DSACS developed an incentive-based system for Antiretroviral Therapy (ART) adherence, incorporating safeguards and robust monitoring. Delhi Government's sustained financial commitment and DSACS programmatic-innovation provide a scalable blueprint for India and global initiatives. Description: This ongoing Delhi Government's scheme focuses on household-economic-strengthening of PLHIV as an incentive for broader behaviour change based-on specific eligibility conditions. Beneficiaries fall into four categories: PLHIV, including children on ART; double orphan HIV positive children (OCI); destitute children living with HIV/in institutional care (DCI); and double orphan ChABH in community-based care in Delhi. Category-wise fixed-monthly financial assistance is released to beneficiaries via direct-bank-transfers leveraging Aadhaar-platform to eliminate corruption. Adherence to treatment is mandatory to continue cash-transfers. Linkages with other schemes established to maximize impact. Lessons learned: In its 11-year evolution, Delhi model has grown from 1110 to 6467 beneficiaries, including 6383 PLHIV, 34 double OCI, 50 DCI, and 27 double orphan ChABH, with 5875 (90.8%) currently active excluding beneficiaries who expired (n=328), migrated/ transferred out of Delhi (n=115), opted-out ART/or lost-to-follow-up (n=135), and 14 CABA who turned major. Steady progress and 98% ART adherence mark positive outcomes. DSACS eased eligibility criteria in 2018, facilitating hurdle-free enrollment, while responding to cost-inflation by enhancing financial assistance, showcasing program adaptability. Achieving >95 ART adherence has significantly boosted survival rates, underscoring program's positive impact on beneficiary health. The scheme's INR 14,69,35,600 expenditure in 2022-23, just 0.13% of Delhi Health Department's plan-outlay, signals a cost-effective investment. Extrapolating this nationally would represent 1.5% of India's Health Ministry's current plan-outlay. Conclusions/Next steps: This innovative model is implementable on large-scale in India and around the globe but requires not only financial commitment but also coordinated efforts, policy adjustments, and collaboration between various stakeholders.

Human papillomavirus (HPV) is a well-known cause of cervical cancer, with HIV infection exacerbating the prevalence of high-risk HPV (HR-HPV) and cervical intraepithelial neoplasia (CIN). ART has been shown to reduce the likelihood of developing squamous intraepithelial lesions (SILs) and HR-HPV prevalence, although its impact on invasive cervical cancer remains inconclusive. In a study in Accra, 250 sexually active HIV-positive women exhibited a high HPV prevalence, emphasising the need for regular screening. HPV testing, visual inspection with acetic acid (VIA), and cytology-based tests are primary screening methods, each with specific advantages and limitations. Cervical cancer rates in sub-Saharan Africa are alarmingly high, necessitating targeted vaccination and prevention strategies.

Short-cycle therapy has proven to be a safe and effective alternative to standard everyday antiretroviral treatment for virally suppressed people living with HIV. Here we report a favorable long-term virological and immunological outcome in 12 virally suppressed people on short cycle therapy with bictegravir/emtricitabine/tenofovir alafenamide administered five days a week (Monday to Friday).

During HIV-1 virus assembly the genomic RNA (vRNA) is selected for packaging by the viral protein Gag because it contains a specific packaging signal, Psi. While there have been numerous studies of Gag-Psi interactions, there is almost no information on kinetic aspects of this interaction. We have investigated the kinetics of Gag binding to different RNAs using switchSENSE DRX2 technology. We measured the association rate of Gag binding to monomeric Psi, to a “Multiple Binding Site Mutant” Psi that is inactive for genome packaging in vivo, and to a scrambled Psi. We discovered that Gag binds more rapidly to Psi RNA than to the mutant or scrambled RNAs. Furthermore, rapid Gag association kinetics are retained within sub-regions of Psi: Gag associates more rapidly with RNA containing only the 3’ two of the three Psi stem-loops than with monomeric RNA containing the 5’ two stem-loops or a scrambled RNA. No differences were detectable with individual Psi stem-loops. Interestingly, the rate of binding of Gag molecules to Psi increases with increasing Gag concentration, suggesting cooperativity in binding. The results are consistent with the hypothesis that selectivity in packaging derives from kinetic differences in initiation of particle assembly.

Abstract: (1) Background: We determined the prevalence of hepatitis B virus (HBV) amongst people without human immunodeficiency virus (HIV) in rural and peri-urban areas in Botswana. (2) Methods: We screened hepatitis B surface antigen (HBsAg) from archived plasma samples of people without HIV (n=2135) randomly selected from the Botswana Combination Prevention Program (BCPP) (2013–2018). We sequenced 415 bp of the surface region using BigDye sequencing chemistry. (3) Results: The median age of participants was 31 (IQR: 24–46) and 64% (1360/2135) were female. HBsAg prevalence was 4.0% (86/2135) [95% CI: 3.3 – 4.9]) and ranged between 0%–9.2%. Older participants (>35 years) had increased odds of HBsAg positivity (OR: 1.94; 95% CI: [1.32–2.86]; p = 0.001. Thirteen samples were sequenced and 7 (53.8%) were genotype A, 3 (23.1%) were genotype D and genotype E each. Clinically significant mutations were identified in the surface region, but no classic drug resistance mutations were identified. (4) Conclusions: We report an HBV prevalence of 4.0% (95% CI 3.3 – 4.9) among people without HIV in rural and pe-ri-urban communities in Botswana with varying rates in different communities. A comprehen-sive national HBV program is required in Botswana to guide HBV prevention, testing and management.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individual’s resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled, re-vaccinated with two doses of Shanchol™ regardless of previous vaccination and followed-up for 90 days. Bloods collected at baseline before re-vaccination, at day 14 prior to second dosing and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60 and 90 across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

Introduction: It is widely recognized that young female sex workers (YFSWs) are at greater risk of HIV infection than their older counterparts. This study aims to unravel the complexities surrounding HIV transmission among this demographic group, by determining the prevalence of HIV infection and identifying high-risk sexual practices associated with HIV infection among YFSWs in Lubumbashi, in the Democratic Republic of the Congo. Methods: We conducted an analytical cross-sectional study and used a comprehensive sample of all YFSWs who presented to the HIV/Sexually Transmitted Infections Screening and Treatment Center in Lubumbashi between April 2016 and December 2017. We collected data on age, number of years in the practice of selling sex, number of sexual encounters per day, number of clients per week, systematic condom use, having suffered from sexually transmitted infections in the last 3 months before the survey, regular alcohol consumption, having anal sex in the last 12 months, having had forced sex in the last 12 months. Multiple logistic regression was used to identify potential factors associated with HIV infection. Results: A total of 572 YFSWs were included in the study, 19 of whom were HIV-positive (3.3%; 95% CI: 2.1% - 5.1%). Participants who were forced to have sex (adjusted OR=12.2; 95% CI: 3.2 - 46.4; p&lt;0.0001), those who did not use condoms systematically (adjusted OR=4.1; 95% CI: 1.3 - 13.0; p=0.018), and those who had anal sex (adjusted OR=23.8; 95% CI: 6.9 - 82.4; p&lt;0.0001) were more likely to be HIV-positive. Conclusion: The results of this study suggest that HIV prevalence among YFSW is higher than in the general Congolese population, and is significantly associated with high-risk sexual practices. Interventions aimed at increasing YFSW’s knowledge of high-risk behaviors should be vigorously pursued.

The human immunodeficiency virus (HIV) continues to pose a significant global health challenge, with millions of people affected and new cases emerging each year. While various treatment and prevention methods exist, including antiretroviral therapy and non-vaccine approaches, developing an effective vaccine remains the most crucial and cost-effective solution to combat the HIV epidemic. Despite significant advancements in HIV research, the HIV vaccine field has faced numerous challenges, and only one clinical trial has demonstrated a modest level of efficacy. This review delves into the history of HIV vaccines and the current efforts in HIV prevention, emphasizing pre-clinical vaccine development using the non-human primate model (NHP) of HIV infection. NHP models offer valuable insights into potential preventive strategies for combating HIV, and they play a vital role in informing and guiding the development of novel vaccine candidates before they can proceed to human clinical trials.

Background: Currently, a Dolutegravir (DTG)-based regimen is administered to women on option B plus to prevent mother-to-child transmission (MTCT) of the virus. However, its effect on reducing MTCT of human immunodeficiency virus (HIV) among exposed infants over the previously used Efavirenz (EFV)-based regimen is unknown. Objective: This study aimed to compare the effects of DTG-based and EFV-based regimens on the MTCT of HIV among exposed infants in southern Ethiopia. Methods: A retrospective before-after study design was employed from March to May 2023 among 958 mother-infant pairs (479 on EFV-based and 479 on DTG-based regimens) enrolled in the prevent mother-to-child transmission (PMTCT) care from September 2015 to February 2023. The outcome variable was the HIV infection status among the exposed infants. A log-binomial model was employed and the proportion was computed to compare the incidence of MTCT of HIV in both groups. The risk ratio (RR) with 95% confidence interval (CI) was calculated to assess the predictor variables. Results: Mothers on a DTG-based regimen were approximately 44% (adjusted risk ratio (aRR): 0.56; 95% CI: 0.44, 0.70) less likely to transmit HIV to their infants than those on an EFV-based regimen. In addition, poor/fair adherence to antiretroviral therapy (ART) (aRR: 5.82; 95% CI: 3.41, 9.93), home delivery (aRR: 3.61; 95% CI: 2.32, 5.62), mixed feeding practice (aRR: 1.83; 95% CI: 1.45, 2.3), and not receiving antiretroviral prophylaxis (aRR: 3.26; 95% CI: 1.6, 6.64) were found to increase the risk of MTCT of HIV infection, whereas older maternal age (aRR: 0.93; 95% CI: 0.9, 0.96) was a protective factor.Conclusion: The Dolutegravir-based regimen significantly reduced MTCT of HIV among exposed infants compared to the EFV-based regimen. Thus, DTG-based first-line ART regimen supplementation should be sustained to achieve global and national targets for zero new infections in HIV-exposed infants.

Despite advancements in antiretroviral therapy (ART) that reduces the viral load to undetectable levels, viral eradication has not been achieved due to HIV-1 persistence in resting CD4+ T-cells. We, therefore, characterized the tat gene, which is essential for HIV-1 replication, from 20 viro-logically controlled HIV-infected (HIV+) older patients on long-term ART with improved CD4+ T-cell counts. PBMC genomic DNA from HIV+ patients were used to amplify tat gene by PCR fol-lowed by nucleotide sequencing and analysis. Phylogenetic analysis showed that each patient’s tat sequences were confined to their own subtrees and well discriminated from other patients’ sequences. Moreover, there was a low degree of viral heterogeneity and lower estimates of genetic diversity within these patients’ tat sequences. Most patients’ Tat deduced amino acid sequences showed intact open reading frames and maintained the important functional domains for Tat functions, including transactivation, TAR binding and nuclear localization. Furthermore, Tat deduced amino acid sequences showed variation in previously characterized cytotoxic T lym-phocytes (CTL) epitopes, suggesting escape mutants. In conclusion, a low degree of genetic varia-bility and conservation of functional domains and variations in CTL epitopes were the features of tat sequences from 20 HIV+ older patients with undetectable viral load on long-term ART.

HIV-1 infection can activate the expression of human endogenous retroviruses (HERVs), particularly HERV-K (HML-2). HIV controllers (HICs) are rare people living with HIV (PLWH) who naturally control HIV-1 replication. The ability of HICs to control the expression of endogenous retroviruses has not been previously addressed. In this study, we measured ERVK-6 RNA expression in PBMCs of HICs (n = 23), antiretroviral (ART)-suppressed subjects (n = 8), and HIV-1-negative (NEG) individuals (n = 10) and correlated the transcript expression of ERVK-6 with multiple HIV-1 restriction factors. Our study reveals that ERVK-6 RNA expression in PBMCs from HICs was significantly downregulated compared with both ART and NEG control groups. Moreover, we detected that ERVK-6 RNA levels in PBMCs across all groups were negatively correlated with the expression levels of p21 and MCPIP1. In our previous study, these two cellular restriction factors were upregulated in HICs compared with control groups. Interestingly, p21 and MCPIP1 limit the activation of macrophages and T cells by downregulating the activity of NF-kB, a transcription factor that stimulates the LTR-driven transcription of HIV-1 and HERV-K proviruses. These findings support that HICs activate innate antiviral mechanisms that may simultaneously downregulate the transcription of both HIV-1 and endogenous retroviruses.

In the 21st century, the effects of HIV-associated neurocognitive disorders (HAND) have been significantly reduced in individuals due to the development of antiretroviral therapies (ARTs). However, the growing epidemic of polysubstance use (PSU) has led to concern for the effects of PSU on HIV-seropositive individuals. To effectively treat individuals affected by HAND, it is critical to understand the biological mechanisms affected by PSU including identification of novel markers. To fill this important knowledge gap, we used an in vivo HIV-Transgenic (HIV-Tg) animal model, to investigate the effects of the combined use of chronic methamphetamine (METH) and oxycodone (oxy). RNA-Seq analysis on the striatum - a brain region that is primarily targeted by both HIV and drugs of abuse - identified key differentially expressed markers post-METH and oxy exposure. Furthermore, ClueGO analysis and Ingenuity Pathway Analysis (IPA) revealed crucial molecular and biological functions associated with ATP-activated adenosine receptor, neuropeptide hormone activity, and the oxytocin signaling pathway to be altered between the different treatment groups. The current study further reveals the harmful effects of chronic PSU and HIV infection that can subsequently impact neurological outcomes in polysubstance users with HAND.

The Virus HIV-1 infection still represents a serious disease even if actually it is transformed in chronic pathology. Considering the crucial role of the enzyme Protease in life cycle of HIV many efforts have been made in the research of new organic compounds showing inhibitory activity. After development of several series of non peptidic inhibitors we report here the synthesis of novel simple HIV-Protease inhibitors containing heteroaryl carboxamides and their antiviral activity in vitro and in HEK293 cells. Benzofuryl- benzothienyl- and indolyl rings as well as aryl sulfonamides with different electronic properties have been introduced by efficient synthetic procedures. All compounds showed inhibitory activity similar to the commercial drug Darunavir, effective against both wild-type HIV-1 protease and that containing the V32I or V82A mutations. ADME properties were also evaluated, showing the potential of such compounds to be developed as drugs.

PG16 is a broadly neutralizing antibody that binds to the gp120 subunit of the HIV-1 Env protein. The major interaction site is formed by the unusually long complementarity determining region (CDR) H3. The CDRH3 residue Tyr100H is known to represent a tyrosine sulfation site; however, this modification is not present in the experimental complex structure of PG16 with full-length HIV-1 Env. To investigate the role of sulfation for this complex, we modeled the sulfation of Tyr100H and compared the dynamics and energetics of the modified and unmodified complex by atomistic molecular dynamics simulations. Our results show that sulfation does not affect the overall conformation of CDRH3, but still enhances gp120 interactions both at the site of mutation and for the neighboring residues. This stabilization affects not only protein-protein contacts, but also the interactions between PG16 and the gp120 glycan shield. Further, we also investigated whether PG16-CDRH3 is a suitable template for the development of peptide mimetics. For a peptide spanning residues 93-105 of PG16 we obtained an experimental EC50 value of 3nM for the binding of gp120 to the peptide. This affinity can be enhanced by almost one order of magnitude by artificial disulfide bonding between residues 99 and 100F. In contrast, any truncation results in significantly lower affinity, suggesting that the entire peptide segment is involved in gp120 recognition. Their high affinity makes PG16-derived peptides useful building blocks for further optimization to obtain a potent inhibitor that efficiently blocks HIV-1 infection.

The COVID-19 pandemic and associated lockdown measures have been associated with substantial disruptions to health care services, including screening for human immunodeficiency virus (HIV) and management of people living with HIV (PLWH). Methods: Data from 3265 patients were examined in a retrospective cohort study. We compared outpatient follow-up for PLWH, the number of new patients, treatment adherence, hospitalizations, and deaths during the “pandemic period” (March 2020 to February 2021) to the “pre-pandemic period” (the equivalent timeframe in 2019) and the “post-pandemic period” (March to September 2021). Results: During the pandemic period, the number of new patients seen at the HIV clinic (116), as well as the requested viral load tests (2414), decreased significantly compared to the pre-pandemic (204 and 2831, respectively) and post-pandemic periods (146 and 2640, respectively)(p<0.01 for all the comparisons). However, across the three study periods, the number of drug refills (1385, 1330, 1411, respectively), the number of patients with undetectable viral loads (85%, 90%, 93%, respectively), and the number of hospital admissions among PLWH remained constant. Conclusions: Despite the COVID-19 pandemic impact, our findings show stability in the retention of clinical care, adherence to treatment, and viral suppression of PLWH, with no significant impact on hospitalization rates and all-cause mortality.

HIV-associated neurocognitive disorder (HAND) is an array of neurocognitive changes associated with HIV infection, and the roles of microRNAs in HAND are not completely revealed yet. Based on published data and publicly available databases, we constructed an integrated miRNA-mRNA network involved in HAND. Bioinformatics analyses, including gene ontology, network analysis, and KEGG pathway analysis, were applied for further study of the network and the genes of the network. The axon guidance KEGG pathway, three genes NTNG1, EFNB2, CXCL12, and 17 miRNAs which regulates them, are spotlighted in our study. This study provides new perspectives to the knowledge of miRNAs’ roles in the process of HAND, and our findings provided potential therapeutic targets and clues of HAND.

The purpose of this study was to identify the factors that affect the mortality among adult HIV/TB co-infected patients and to see the nutritional difference among mortality in residence level. Retrospective cohort studies of 417 patients which fulfill our criteria were included. Multilevel logistic regression models were used. MLwiN and SPSS software are used to estimate the parameter. The variance of the random factor in the empty model was significant which indicates that there were residential differences in TB-HIV co-infected mortality and it shows multilevel analysis was an appropriate approach for further analysis. The prevalence of HIV/TB co-infected patients' death was 12.9% in study time. Functional status, age of patients, WHO clinical stages, nutritional status, CD4 counts, regimen, and BMI were found to be significant determinants of HIV/TB co-infected mortality. In our study, patients with the bedridden category of functional status, the fourth stages of WHO clinical stages (stage IV), patients with higher age, patients whose treatments were second-line regimen and low CD4 cell counts were more at risk of death. The study also revealed that; poor nutritional status increased the risk of mortality among HIV/TB co-infected patients and it varies among the residence of the patients (rural area were more at risk).

Immune complexes (ICs) made of antibody-bound antigens exhibit immunomodulatory activities exploitable in a vaccination strategy to optimize vaccine efficacy. The modulatory effects of ICs are typically attributed to the Fc fragments of the antibody components, which engage Fc receptors, complement and complement receptors on various immune cells. These Fc-mediated functions facilitate the critical interplay between innate and adaptive immune systems to impact the quality and quantity of the elicited adaptive responses. In addition to the Fc contribution, the Fab fragment also plays an immunoregulation role. The antigen-binding domains of the Fab fragment can bind their specific epitopes at high affinity to sterically occlude these antigenic sites from recognition by other antibodies. Moreover, the Fab-mediated binding have been demonstrated to induce allosteric alterations at nearby or distant antigenic sites. In this review article, we survey published studies to illuminate how the immunomodulatory functions of ICs have been investigated or utilized in a vaccination strategy to fight against an array of infectious pathogens, culminating with IC vaccine designs aimed at preventing HIV-1 infection. In particular, we highlight IC vaccine candidates that exploit Fab-mediated steric and allosteric effects to direct antibody responses away or toward the V1V2 domain, the V3 loop, and other antigenic sites on the HIV-1 envelope gp120 glycoprotein. Like other HIV-1 vaccine approaches, the path for IC-based vaccines to reach the clinic faces major hurdles yet to be overcome; however, investigations into this vaccine strategy have provided insights into the multifaceted activities of antibodies beyond their conventional roles in the host defense against HIV-1 and other microbial pathogens.

The HIV-1 nef gene terminates in a 3’-UGA stop codon, which is highly conserved in the main group of HIV-1 subtypes, along with a downstream potential coding region that could extend the nef protein by 33 amino acids, if readthrough of the stop codon occurs. Antisense tethering interactions (ATIs) between a viral mRNA and a host selenoprotein mRNA are a potential viral strategy for the capture of a host selenocysteine insertion sequence (SECIS) element (Taylor et al, 2016) [1]. This mRNA hijacking mechanism could enable the expression of virally encoded selenoprotein modules, via translation of in-frame UGA stop codons as selenocysteine (SeC). Here we show that readthrough of the 3’-terminal UGA codon of nef occurs during translation of HIV-1 nef expression constructs in transfected cells. This was accomplished via fluorescence microscopy image analysis and flow cytometry of HEK 293 cells, transfected with engineered GFP reporter gene plasmid constructs, in which GFP can only be expressed by translational recoding of the UGA codon. SiRNA knockdown of thioredoxin reductase 1 (TR1) mRNA resulted in a 67% decrease in GFP expression, presumably due to reduced availability of the components involved in selenocysteine incorporation for the stop codon readthrough, thus supporting the proposed ATI. Addition of 20 nM sodium selenite to the media significantly enhanced stop codon readthrough in the pNefATI1 plasmid construct, by >100%, supporting the hypothesis that selenium is involved in the UGA readthrough mechanism.

The high mutation rate of human immunodeficiency virus type 1 (HIV-1) plays a major role in treatment resistance from the development of vaccines to long-lasting drugs. In addressing the crux of the issue, various attempts to estimate the mutation rate of HIV-1 resulted in a large range of 10-5 - 10-3 errors/bp/cycle due to the use of different types of investigation methods. In this review, we discuss the different assay methods, their findings on the mutation rates of HIV-1 and how the location of these mutations can be further analyzed for their potential allosteric effects to reveal potentially new inhibitors with different pharmacodynamics that can be used to circumvent fast occurring HIV drug resistance. Given that HIV is one of the fastest mutating viruses, it is a good model for comprehensive study of its mutations that can give rise to much horizontal understanding towards overall viral drug resistance as well as emerging viral diseases.

DNA vaccines are stable, safe, cost effective to produce and relatively quick and easy to manufacture. However, to date DNA vaccines have shown relatively poor immunogenicity in humans despite promising preclinical results. Consequently, a number of different approaches have been investigated to improve the immunogenicity of DNA vaccines. These include the use of improved delivery methods, adjuvants, stronger promoters and enhancer elements to increase antigen expression, and codon optimization of the gene of interest. This review describes the creation and use of a DNA vaccine vector containing a porcine circovirus (PCV-1) enhancer element that significantly increases recombinant antigen expression and immunogenicity and allows for dose sparing. A 172bp region containing the PCV-1 capsid protein promoter (Pcap) and a smaller element (PC; 70 bp) within this were found to be equally effective. DNA vaccines containing the Pcap region expressing various HIV-1 antigens were found to be highly immunogenic in mice, rabbits and macaques, at 4 to 10-fold lower doses than normally used and to be highly effective in heterologous prime-boost regimens. By lowering the amount of DNA used for immunization, safety concerns over injecting large amounts of DNA into humans can be overcome.

(1) Background: We aimed to determine the prevalence of hepatitis B virus (HBV) resistance-associated mutations (RAMs) in people with HBV and human immunodeficiency virus (HBV/HIV) in Botswana. (2) Methods: We sequenced HBV from participants with HBV/HIV from the Botswana Combination Prevention Project study (2013-2018) using the Oxford Nanopore GridION platform. Consensus sequences were analyzed for genotypic and mutational profiles. (3) Results: Overall, 98 HBV sequences had evaluable reverse transcriptase region coverage. The median participant age was 43 years (IQR: 37, 49) and 66/98 (67.4%) were female. Most participants, 85/97 (87.6%) had suppressed HIV viral load (VL). HBV RAMs were identified in 61/98 (62.2%) participants. Most RAMs were in positions 204 (60.3%), 180 (50.5%) and 173 (33.3%), mostly associated with lamivudine resistance. The triple mutations, rtM204V/L180M/V173L and was the most predominant (17/61 [27.9%]). Most participants (96.7%) with RAMs were on antiretroviral therapy for a median duration of 7.5 years (IQR: 4.8, 10.5). Approximately 27.9% (17/61) of participants with RAMs had undetectable HBV VL, 50.8% (31/61) had VL &lt;2000IU/mL and 13/61 (21.3%) had VL ≥2000 IU/mL. (4) Conclusions: The high prevalence of lamivudine RAMs discourages the use of ART regimens with 3TC as the only HBV-active drug in people with HIV/HBV.

The tiered laboratory framework for HIV viral load monitoring accommodates a range of HIV viral load testing platforms, with quality assessment critical to ensure quality patient testing. HIV plasma viral load testing is challenged by the instability of viral RNA. An approach using an RNA stabilizing buffer is described for the Xpert® HIV-1 Viral Load (Cepheid) assay and was tested in remote laboratories in South Africa. EDTA-plasma panels with known HIV viral titres were prepared in PrimeStore molecular transport medium for per-module verification and per-instrument external quality assessment. The panels were transported at ambient temperatures to 13 testing laboratories during 2017 and 2018, tested according to standard procedures and uploaded to a web portal for analysis. A total of 275 quality assessment specimens (57 verification panels and two EQA cycles) were tested. All participating laboratories met study verification criteria (n=171 specimens) with an overall concordance correlation coefficient (ρ_c) of 0.997 (95% confidence interval [CI]: 0.996 to 0.998) and a mean bias of -0.019 log cp/mL (95% CI: -0.044 to 0.063). The overall EQA ρ_c (n=104 specimens) was 0.999 (95% CI: 0.998 to 0.999), with a mean bias of 0.03 log cp/mL (95% CI: 0.02 to 0.05). These panels are suitable for use in quality monitoring of Xpert® HIV-1 VL and are applicable to laboratories in remote settings.

Tissue resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8 TRM, there has been recently an increased interest in defining the phenotype and the role of CD4 TRM in diseases. Circulating CD4 T cells seed tissue CD4 TRM, but there also appears to be an equilibrium between CD4 TRM and blood CD4 T cells. CD4 TRM are more mobile than CD8 TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8 TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4 and CD8 TRM persisting between lesions may control asymptomatic shedding through interferon gamma secretion, although this has been more clearly shown for CD8 T cells. The exact role of the CD4/CD8 TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4 TRM have now been shown to be a major target for productive and latent infection in cervix. In HSV and HIV co-infections, CD4 TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4 TRM and their induction by vaccines may help control sexual transmission by both viruses.

The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral Integrase (IN) enzyme catalyses integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG) and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of Integrase Strand Transfer Inhibitors (INSTIs). In this study, we applied computational methods of molecular modelling and docking to analyse the effect of NOPs on the full-length IN structure and INSTI binding. We identified 16 NOPs within the Cameroonian derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any effect on INSTI binding. INSTIs displayed similar binding affinities to each IN structure. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment naïve populations. This study supports the use of second-generation INSTI DTG as part of first-line combination antiretroviral therapy (cART) regimens, due to DTG possessing a stronger genetic barrier to the emergence of drug resistance.

For the diagnosis of disease, the ability to quantitatively detect trace amounts of the causal proteins from bacteria/viruses as biomarkers in patient specimens is highly desirable. Here we introduce a simple, rapid, and colorimetric assay as a de novo, ultrasensitive detection method. This ultrasensitive assay consists of sandwich enzyme-linked immunosorbent assay (ELISA) and thionicotinamide-adenine dinucleotide (thio-NAD) cycling, forming an ultrasensitive ELISA, in which the signal substrate (i.e., thio-NADH) accumulates in a triangular manner, and the accumulated thio-NADH is measured at its maximum absorption wavelength of 400 nm. We have successfully achieved a limit of detection of ca. 10–18 moles/assay for a target protein. As an example of infectious disease detection, HIV-1 p24 could be measured at 0.0065 IU/assay (i.e., 10⁻¹⁸ moles/assay), and as a marker for a lifestyle-related disease, adiponectin could be detected at 2.3 × 10⁻¹⁹ moles/assay. In particular, despite the long-held belief that the trace amounts of adiponectin in urine can only be detected using a radioisotope, our ultrasensitive ELISA was able to detect urinary adiponectin. This method is highly versatile, because simply changing the antibody enables the detection of various proteins. This assay system requires only the measurement of absorbance, thus it requires equipment that is easily obtained by medical facilities, which facilitates diagnosis in hospitals and clinics. Moreover, we describe an expansion of our ultrasensitive ELISA to a non-amplification nucleic acid detection method for nucleic acids using hybridization. These de novo methods will enable simple, rapid, and accurate diagnosis.

This economic evaluation aims to support policy-making on the combined use of pre-exposure prophylaxis (PrEP) with HIV vaccines by evaluating the potential cost-effectiveness of implementation that would support the design of clinical trials for assessment of combined product safety and efficacy. The target study population is a cohort of men who have sex with men (MSM) in the United States. Policy strategies considered include standard HIV prevention, daily oral PrEP, HIV vaccine, and their combination. We constructed a Markov model based on clinical trial data and published literature. We used a payer perspective, monthly cycle length, a lifetime horizon, and a 3% discount rate. We assumed a price of $500 per HIV vaccine series in the base case. HIV vaccines dominated standard care and PrEP. At current prices,PrEP was not cost-effective alone or in combination. A combination strategy had the greatest health benefit but was not cost-effective (ICER=$463,448/QALY) as compared to vaccination alone. Sensitivity analyses suggest a combination may be valuable for higher-risk men with good adherence. Vaccine durability and PrEP drug prices were key drivers of cost-effectiveness. Results suggest that boosting potential may be key to HIV vaccine value.

Mortality in children accounts for 15% of all AIDS-related deaths globally, with a higher burden among Cameroonian children (25%), likely due to poor virological response. We sought to evaluate viral suppression (VS) and its determinants in a nationally representative paediatric and young adult population receiving antiretroviral therapy (ART). A cross-sectional and multicentric study was conducted among Cameroonian children (

Objective: This study assessed hearing aid benefits for people with a normal audiogram but hearing-in-noise problems in everyday listening situations. Design: Exploratory double-blinded case control study whereby participants completed retrospective questionnaires, ecological momentary assessments, speech-in-noise testing, and mental effort testing with and without hearing aids. Twenty-seven adults reporting speech-in-noise problems but normal air-conduction pure-tone audiometry took part in the study. They were randomly separated into an experimental group who trialled mild-gain hearing aids with advanced directional processing and a control group fitted with hearing aids with no gain or directionality. Results: Self-reports showed mild-gain hearing aids reduce hearing-in-noise difficulties and provide a better hearing experience (i.e., improved understanding, participation, and mood). Despite the self-reported benefits, the laboratory tests did not reveal a benefit from the mild-gain hearing aids, with no group differences on speech-in-noise tests or mental effort measures. Further, participants found the elevated cost of hearing aids to be a barrier for their adoption. Conclusions: Hearing aids benefit the listening experience in some listening situations for people with normal audiogram who report hearing difficulties in noise. Decreasing the price of hearing aids may lead to greater accessibility to those seeking remediation for their communication needs.

(1) Background: The COVID-19 pandemic has raised concerns about the impact of underlying medical conditions on the health outcomes of people living with HIV (PLWH). This study aimed to assess how pre-existing chronic medical conditions affect the health outcomes of PLWH infected with COVID-19. (2) Methods: A retrospective study using data from the Minnesota Fairview network (January 1, 2020 - December 31, 2022) was conducted. Fisher’s Exact Test, Kruskal-Wallis rank sum test, and ordinal logistic regressions with Benjamini-Hochberg (BH) adjustment on p-values were used to assess the influence of chronic conditions on COVID-19 severity, adjusting for age and gender. (3) Results: Among 216 records, significant associations were found for stroke, chronic kidney disease, lung disease, and neurologic conditions (p<0.05). Type 1 diabetes was marginally significant (0.05<p<0.1). After adjusting for age and sex, stroke (p=0.0008, BH-adjusted p=0.0044) and chronic kidney disease (p=0.0003, BH-adjusted p=0.0033) significantly increased the risk of severe COVID-19 outcomes. (4) Conclusions: Pre-existing medical conditions should be considered in the clinical management and public health interventions for PLWH with COVID-19. Tailored strategies are essential to mitigate the higher risk of severe outcomes in PLWH with specific chronic comorbidities.

(1) Background: Hepatitis B virus (HBV) sequencing data are important for monitoring HBV evolution. We aimed to molecularly characterize HBV sequences from participants with HBV surface antigen (HBsAg+) positive serology and occult hepatitis B infection (OBI+). (2) Methods: We utilized archived plasma samples from a cohort of people living with (PLWH) in Botswana. HBV DNA was sequenced, genotyped and analyzed for mutations. We compared mutations from study sequences to those from previously generated HBV sequences in Botswana. The impact of OBI-associated mutations on protein function was assessed using the Protein Variation Effect Analyzer. (3) Results: Sequencing success was higher in HBsAg+ than OBI+ samples [86/128 (67.2%) vs 21/71 (29.2%)]. Overall, 93.5% (100/107) sequences were genotype A1, 2.8% (3/107) were D3 and 3.7% (4/107) were E. We identified 13 escape mutations in 18/90 (20%) sequences with HBsAg coverage, with K122R having the highest frequency. The mutational profile of current sequences differed from previous Botswana HBV sequences, suggesting possible mutational changes over-time. Mutations deemed to have an impact on protein function were tpQ6H, surfaceV194A and preCW28L. (4) Conclusions: We characterized HBV sequences from PLWH in Botswana. Escape mutations were prevalent and were not associated with OBI. Longitudinal HBV studies are needed to investigate HBV natural evolution.

MicroRNAs (miRNAs) play important roles in the control of HIV-1 infection. Here, we performed RNAseq profilings of miRNAs and mRNAs expressed in CD4+ T-lymphocytes upon HIV-1 infection. Our results reveal significant alterations of miRNAs and mRNAs expression profiles in infected relative to uninfected cells. One of the miRNAs markedly downregulated in infected cells is miRNA-26a. Among the putative targets of miRNA-26a are CD59 receptor transcripts, which are significantly upregulated in infected CD4+ T-cells. Addition of miRNA-26a mimics to CD4+ T-cells reduces CD59 at both mRNA and surface protein levels, validating CD59 as a miRNA-26a target. Consistent with the reported inhibitory role of CD59 in complement-mediated lysis (CML), knocking-out CD59 in CD4+ T-cells renders both HIV-1 infected cells and progeny virions more prone to antibody-dependent CML (ADCML). Addition of miRNA-26a mimics to infected cells leads to enhanced sensitivity of progeny virions to ADCML, a condition linked to a reduction of CD59 packaging into released virions. Lastly, HIV-1-mediated downregulation of miRNA-26a expression is shown to be dependent on integrated HIV-1 expression but does not involve viral accessory proteins. Overall, these results highlight a novel mechanism by which HIV-1 limits ADCML by upregulating CD59 expression via miRNA-26a downmodulation.

Background: Although antiretroviral therapy (ART) effectively halt disease progression in HIV infections, complete eradiation of the virus remains elusive. Additionally, challenges such as long-term ART toxicity, drug resistance, and the demanding regimen of daily and lifelong ad-herence required by ART highlight the imperative need for alternative therapeutic and preventa-tive approaches. In recent years, broadly neutralizing antibodies (bNAbs) have emerged as promising candidates, offering potential for therapeutic, preventative and possibly curative in-terventions against HIV infection. Objective: This review aims to provide a comprehensive overview of the current state of knowledge regarding the passive immunization of bNAbs in HIV-1 infected individuals. Main findings: Recent findings from clinical trials have highlighted the potential of bNAbs in treatment, prevention, and in the quest of an HIV-1 cure. While monotherapy with a single bNAb is insufficient in maintaining viral suppression and preventing viral escape, ultimately leading to viral rebound, combination therapy with potent, non-overlapping epitope-targeting bNAbs have demonstrated prolonged viral suppression and delayed time to rebound by effec-tively restricting the emergence of escape mutations, albeit largely in individuals with bNAb-sensitive strains. Additionally, passive immunization of bNAb have provided ‘proof-of-concept’ for antibody-mediated prevention against HIV-1 acquisition, although com-plete prevention was not obtained. Therefore, further research on the use of bNAbs in HIV-1 treatment and prevention remains imperative.

Cystatin F (CstF) is a protease inhibitor of cysteine cathepsins, including those involved in acti-vating the perforin/granzyme cytotoxic pathways. It is targeted to the endolysosomal pathway but can also be secreted to the extracellular milieu or endocytosed by bystander cells. CtsF was shown to be significantly increased in tuberculous pleurisy, and during HIV coinfection, pleural fluids display high viral loads. In human macrophages, we revealed a strong upregulation of CstF during infection with Mycobacterium tuberculosis (Mtb). CstF manipulation using RNA si-lencing led to increased proteolytic activity of lysosomal cathepsins, improving Mtb intracellular killing. Here, we investigate the impact of CstF depletion during coinfection of Mtb-infected mac-rophages with lymphocytes infected with HIV. Our results indicate that decreasing CstF released by phagocytes impacts the major pro-granzyme convertase cathepsin C of cytotoxic immune cells. Consequently, an observed increase of the granzyme B apoptotic effects leads to a significant re-duction in viral replication in HIV-infected lymphocytes. Overall, our results indicate a mecha-nism of Mtb/HIV evasion of the cytotoxic mediated pathogen killing driven by the ax-is CstF/ catC/granzymes contributing to this syndemic interaction. Ultimately, this knowledge can be crucial for developing new therapeutic approaches to control both pathogens based on manipulating CstF.

The prevalence of HIV infections in the province of Papua is rising. The study aimed to examine the effect of a sexual reproductive health-based HIV prevention program on knowledge, subjective norms, and attitudes, as well as the behavior control of reproductive health and HIV prevention. A quasi-experimental study was applied in this study with an equivalent control group. The total of 289 students is divided into the experimental group (n = 134) and the control group (n = 155). The experimental group received the sexual reproductive health-based HIV prevention program. The control group received the routine program from the school. The results found a significant difference in knowledge, subjective norms and attitudes, and behavior control of reproductive health and HIV prevention among intervention groups before and after receiving the Sexual Reproductive Health School-Based HIV Prevention program (p-value

Epitranscriptomic RNA modifications play a crucial role in the posttranscriptional regulation of gene expression. N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic RNA and plays a pivotal role in RNA fate. RNA m6A modification is regulated by a group of cellular proteins, methyltransferases (writers) and demethylases (erasers), which add and remove the methyl group from adenosine, respectively. m6A modification is recognized by a group of cellular RNA-binding proteins (readers) that specifically bind to m6A-modified RNA, mediating effects on RNA stability, splicing, transport, and translation. The functional significance of m6A modification of viral and cellular RNA is an active area of virology research. In this review, we summarize and analyze current literature on m6A modification of HIV-1 RNA, the multifaceted functions of m6A in regulating HIV-1 replication, and the role of viral RNA m6A modification in evading the innate immune responses to infection. Furthermore, we briefly discuss future directions and therapeutic implications of mechanistic studies of HIV-1 epitranscriptomic modifications.

The results of the most recent investigation of triterpenoid-based antiviral agents effective namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong into a series of compound derived from betulin or betulinic acid, and their synthetic derivative called bevirimat. A termination of clinical trials of bevirimat in the Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid or other miscellaneous triterpenoids, are relatively rarely involved in a search for novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.

Abstract: The SARS-CoV-2 pandemic has significantly impacted world health and economic status. In response, much work has been undertaken to provide effective, safe vaccines, antibodies and antiviral drugs with which to address this pandemic. Treatment of a pandemic population presents multiple challenges in addition to the primary issue of drug efficacy and safety, such as large scale drug manufacture and distribution, drug stability, oral dosing and pharmacoeconomic considerations. Ideally, these factors must be addressed if new candidate drugs are to be advanced for treatment of large (pandemic) populations. Subsequently, new antivirals have reached the market but choices are few. According to the NIH Covid Treatment Guidelines, only three small molecule antiviral drugs are available to treat COVID-19 disease. As such, a significant part of the research towards discovery of new antiviral drugs has focused on screening and evaluation of ‘repurposed drugs’ or previously approved or clinical stage drugs. Yet, in spite of this increased research activity, one promising clinical stage candidate drug has received little attention regarding its potential as a monotherapy or component of combination therapy for treatment of COVID-19 disease. Tucaresol, with documented human safety and pharmacokinetic data, is an orally active, stable, small molecule amenable to large scale manufacture by a proprietary two-step synthesis developed by us. Tucaresol functions as a host-targeted antiviral by selective protection/reconstitution of CD4+ T helper cells as demonstrated in HIV patients and SIV macaques. In view of similarities between HIV and SARS-CoV-2, especially with respect to host CD4+ T helper cells, and the suitability of Tucaresol for facile treatment of pandemic populations, Tucaresol is presented herein for treatment of mild-to-moderate COVID-19 patients but may also be useful for treatment of advanced disease accompanied by lymphopenia.

Vaccines against SARS-CoV-2 have been pivotal in overcoming the Covid-19 pandemic yet understanding the subsequent outcomes and immunological effects remain crucial, especially for at-risk groups e.g. people living with human immunodeficiency virus (HIV) (PLWH). In this study we report the longitudinal IgA and IgG antibody titers, as well as antibody-mediated angiotensin converting enzyme 2 (ACE2) binding blockade, against the SARS-CoV-2 spike (S) proteins after 1 and 2 doses of the ChAdOx1 nCoV-19 vaccine in a population of Black PLWH. Here, we report that PLWH (N = 103) did not produce an anti-S IgA response after infection or vaccination, however, anti-S IgG was detected in response to vaccination and infection, with the highest level detected for infected vaccinated participants. The anti-IgG and ACE2 blockade assays revealed that both vaccination and infection resulted in IgG production, however, only vaccination resulted in a moderate increase in ACE2 binding blockade to the ancestral S protein. Vaccination with a previous infection results in the greatest anti-S IgG and ACE2 blockade for the ancestral S protein. In conclusion, PLWH produce an anti-S IgG response to the ChAdOx1 nCoV-19 vaccine and/or infection, and ChAdOx1 nCoV-19 vaccination with a previous infection produced more neutralizing antibodies than vaccination alone.

Rapid progress in gene editing based on clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) has revolutionized the study of gene and genome function and genetic disease correction. While numerous genetically modified cellular and animal models have been created to understand biological processes, the clinical application of CRISPR/Cas tools has been impeded by off-targeting and delivery problems. It is generally accepted that the delivery of CRISPR in the form of a ribonucleoprotein complex (RNP) substantially reduces the time of DNA exposure to the effector nuclease, minimizing off-target effects and facilitating clinical usage. This review focuses on CRISPR/Cas RNP delivery with retro/lentiviral particles and exosomes, whose parallel production by cells transfected with viral vectors is underestimated. We critically evaluate specific mechanisms of extracellular particle formation and loading with CRISPR/Cas for each system. Additionally, the details of Cas-nanoparticle entry and uncoating, previously unappreciated in the context of gene editing efficiency, are discussed. Based on existing knowledge about the consequences of intervention in retroviral assembly, entry, or exosome formation, we outline the potential problems with CRISPR/Cas delivery using extracellular nanoparticles and ways to address them.

Introduction: Pre-Exposure Prophylaxis (PrEP) for HIV prevention has been implemented in several countries. Previous literature has shown that its cost-effectiveness (and, under some specifications, cost-saving character) is dependent on the reduction in price due to generics, the time-horizon and its effectiveness. The intervention has never been studied in Catalonia, a territory with extensive implementation. Methods: Economic evaluation of the implementation of HIV pre-exposition prophylaxis using administrative data from Men who have Sex with Men (MSM) who receive the treatment (at the generic price). A deterministic compartmental model and a social perspective with a micro-costing approach over the time horizon 2022-2062 are used. A baseline 86% effectiveness of PrEP is assumed. Results: Daily oral PrEP is found to be cost-saving: discounted savings in costs are attained after 16 years, and after 40 years they reach 81 million euros. In terms of health indicators, 10,322 additional discounted QALYs are generated by the intervention. Results are sensitive to sexual behavioral patterns among MSM, the price of PrEP (reduced if offered on-demand), its effectiveness and the discount rate. Conclusions: The use and promotion of PrEP in Catalonia is predicted to result in substantial health and monetary benefits because of reductions in HIV infections. Short-term investments in the promotion of PrEP will result in important cost-savings in the long term.

Background: The presence of HIV residual replication markers was investigated among distinct subgroups of individuals on antiretroviral treatment (ART). Methods: One hundred sixteen patients were distributed into 5 treatment groups: first-line suppressive ART with a non-nucleoside analog reverse-transcriptase inhibitor (NNRTI) (n = 26), first-line suppressive ART with boosted protease inhibitors (PI-r) (n = 25), suppressive salvage therapy using PI-r (n = 27), suppressive salvage therapy with PI-r and raltegravir (n = 22) and virologic failure (n = 16). Episomal and total DNA quantitation was evaluated. HIV antibody and LPS quantitation was performed. Results: Episomal DNA was positive in 26% to 38% of individuals under suppressive ART, and it was higher among ART virologic failure group (p = 0.04). HIV proviral load was higher among patients with detectable episomal DNA (p = 0.01). Individuals receiving initial PI-r treatment presented lower HIV antibody (p = 0.027) and LPS (p = 0.029) levels than individuals receiving NNRTI. There was a negative correlation between episomal DNA quantitation and the duration of suppressive ART (p = 0.04), CD4+ T-cell count (p = 0.08), and CD8+ T-cell count (p = 0.07). Conclusions: Residual HIV replication has been inferred among individuals under suppressive ART according to episomal DNA detection. Residual replication may decrease with longer periods of suppressive ART and higher levels of CD4+ and CD8+ T cells. The relationship between episomal DNA and total DNA suggests there is a replenishment of the proviral reservoir. Lower antibody and LPS levels among patients with initial PI-r ART suggest these regimens may more effectively suppress HIV, more effectively decreasing HIV antigenic component.

Recent years have witnessed a breakthrough in identification of a trimer-of-hairpins motif within viral envelopes that triggers a broad range of virus-host fusion. Identifying a domain capable of controlling virus-host fusion remains a challenge due to sequence diversity, heavy glycan shielding and multiple conformations. Here, we report that HR2, a prevalent heptad repeat sequence comprising an alpha-helical coil anchored in viral membranes, is an accessible site to triterpenes, a class of widely distributed natural products. Triterpenes and their derivatives inhibit the entry of Ebola, HIV, and influenza A viruses with distinct structure-activity relationships. Specifically, triterpenoid probes, upon activation by ultraviolet light, capture the viral envelope via crosslinking the HR2 coil. Profiling the Ebola HR2 sequence using amino acid substitution, surface plasmon resonance (SPR) and nuclear magnetic resonance (NMR) spectroscopy disclosed six constitutive residues that are accessible to triterpenoids, leading to wrapping of the hydrophobic helix by triterpenoids and blocking of the HR1-HR2 interaction, which is critical in the trimer-of-hairpins formation. This finding was also observed in the envelopes of HIV and influenza A viruses and might potentially extend to a broader variety of viruses. Our findings might translate into a shared mechanism that host utilize natural product triterpenoids to antagonize membrane fusion of respective viruses, complementing the current repertoire of antiviral agents.