HIV-associated cognitive dysfunction during combination antiretroviral therapy (cART) involves mitochondrial dysfunction, but the impact of contemporary cART on chronic metabolic changes in the brain and in latent HIV infection is unclear. We interrogated mitochondrial function in a human microglia (hμglia) cell line harboring inducible HIV provirus, and in SH-SY5Y cells, after exposure to individual antiretroviral drugs or cART, using the MitoStress assay. cART-induced changes in protein expression, reactive oxygen species (ROS) production, mitochondrial DNA copy number, and cellular iron were also explored. Finally, we evaluated the ability of ROS scavengers or plasmid-mediated overexpression of the antioxidant iron-binding protein, Fth1, to reverse mitochondrial defects. Contemporary antiretroviral drugs, particularly bictegravir, depressed multiple facets of mitochondrial function by 20-30%, with most pronounced effects in latently infected-HIV+ hμglia and SH-SY5Y cells. Latently HIV-infected hμglia exhibited upregulated glycolysis. Increases in total and/or mitochondrial ROS, mitochondrial DNA copy number, and cellular iron accompanied mitochondrial defects in hμglia and SH-SY5Y cells. In SH-SY5Y cells, cART reduced mitochondrial iron-sulfur-cluster-containing supercomplex and subunit expression and increased Nox2 expression. Fth1 overexpression or pre-treatment with N-acetylcysteine prevented cART-induced mitochondrial dysfunction. Contemporary cART impairs mitochondrial bioenergetics in hμglia and SH-SY5Y cells, partly through cellular iron accumulation; some effects differ by HIV latency.

Background: The clinical outcomes of antiretroviral drugs may be modified by drug interactions; thus, it is important to update the drug interactions in people living with HIV. Aim: To update clinically relevant drug interactions in people living with HIV on antiretroviral therapy. Methods: A systematic review in Medline/PubMed database from July 2017 to December 2022, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. The clinical relevance of drug interaction was grouped into 5 levels according to gravity and probability of occurrence. Results: 361 articles were identified and 148 were included, which allowed the identification of 894 drug interaction pairs. Among these 894 drug pairs, 355 have not been identified previously; and 89 (25.1%) and 72 (20.2%) were of levels 1 and 2, respectively. In addition, for 197 (55.5%) pairs the mechanism was pharmacokinetic. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitors (PIs) with 91 (25.6%) and 76 (21.4%) pairs, respectively were more frequent. Conclusions: In people living with HIV on antiretroviral therapy, we identify 355 new drug interaction pairs, of them 161 (45.3%) are assessed as levels 1 and 2 and thus, clinically relevant; a figure that is lower compared to 2014-2107 update. The pharmacokinetic mechanism is the most frequently identified. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitors (PIs) are the antiretroviral groups with the highest number of clinically relevant drug interactions.

South Africa possesses the largest anti-retroviral therapy (ART) program in the world but the path to this record was dramatic. There is scarce literature employing a comprehensive framework to explain this ART policy change and inform current policy making processes. This paper applies the Advocacy Coalition Framework (ACF) to analyse the interactions among diverse actors, institutions and networks that were associated with the ART policy change in South Africa. Post-apartheid, HIV/AIDS and AIDS-related mortality were serious public health problems. At the time, the discernible coalitions in the AIDS policy subsystem were the prescience coalition and AIDS dissidents. In view of the availability of compelling scientific evidence on the pathogenesis of HIV/AIDS, the clinical usefulness of ART, the availability of funding for national ART roll-out, strong global advocacy to reduce the cost of ART, all of these in an era when access to adequate HIV care was increasingly considered a human right, the environment to establish an appropriate ART policy for the country was conducive. However, AIDS dissidents dominated the policy agenda via their control over key institutions, the use of various dimensions of power, biasing evidence to inform policy, and promoting the activities of strong interest groups that were not in support of ART. National ART roll-out ultimately emerged as a political priority as a result of external shocks (on the ART policy subsystem) which disfavoured the dominant coalition. Failure to supplement this application of the ACF with key pubic policy concepts such as power dimensions, evidence use in policy, governance and emergence of global health networks would have led to suboptimal appraisal of the ART policy change and misinformation of current policy making processes.

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.

Distal Sensory Peripheral Neuropathy (DSP) is a common complication in HIV-infected individ-uals, leading to chronic pain and reduced quality of life. Despite antiretroviral therapy (ART), DSP persists, often prompting the use of opioid analgesics, which can paradoxically worsen symptoms through opioid-induced microbial dysbiosis. This study employs the HIV Tg26 mouse model to investigate HIV-DSP development and assess gut microbiome changes in response to chronic morphine treatment and ART using 16s rRNA sequencing. Our results reveal that chronic morphine and ART exacerbate HIV-DSP in Tg26 mice, primarily through mechanical pain path-ways. As the gut microbiome may be involved in chronic pain persistence, microbiome analysis indicated distinct bacterial community changes between WT and Tg26 mice as well as morphine and ART-induced microbial changes in the Tg26 mice. This study reveals the Tg26 mice model to be a relevant system that can help elucidate the pathogenic mechanisms of opioid and ART-induced exacerbation of HIV-associated pain. Our results shed light on the intricate inter-play between HIV infection, ART, opioid use, and the gut microbiome in chronic pain development. They hold implications for understanding the mechanisms underlying HIV-associated pain and microbial dysbiosis, with potential for future research focused on prevention and treatment strategies.

Young people living with perinatal infections of Human Immunodeficiency Virus (YLPHIV) face a chronic disease, with treatment including adherence to life-long antiretroviral treatment (ART). The aim of this QES was to explore adherence to ART for YLPHIV as an assemblage within the framework of the BPS model with a new materialist perspective. We searched up to November 2021 and followed the ENTREQ and Cochrane guidelines for QES. All screening, data extraction and critical appraisal was done in duplicate. We analysed and interpreted the findings innovatively, by creating images of meaning, a storyboard, and storylines. We then reported the findings in a narrative first person story. We included 47 studies and identified 9 storylines. We found that treatment adherence has less to do with humans’ preferences, motivations, needs and dispositions, and more to do with how bodies, viruses, things, ideas, institutions, environments, social processes, and social structures assemble. This QES highlights that adherence to ART for YLPHIV is a multisensorial experience in a multi agentic world. Future research into rethinking the linear and casual inferences we are accustomed too in evidence-based health care is needed if we are to adopt multidisciplinary approaches to address pressing issues such as adherence to ART.

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.

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.

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.

I. Introduction: Adherence to ART reduces morbidity and mortality among PLHIV by suppression of viral replication, restoration and preservation of immune function. However, poor adherence may lead to treatment failure and death. PLHIV have high probability of treatment interruptions due to lockdowns related to COVID-19 protocol. Mortality rate is higher among COVID-19 patients with HIV than those with COVID-19 only. This led to determination of the barriers to antiretroviral medication adherence in PLHIV at the time of COVID-19 pandemic and seek significant association between identified HIV treatment barriers and socio-demographic characteristics. II. Methods: A cross-sectional study using online survey questionnaire was distributed via social media. Sample size was computed using Open Epi software. Data was analyzed using Stata software. Categorical variables and quantitative data were summarized using frequencies and percentages, and mean and standard deviation respectively. Chi-square test or Fisher’s exact test, whichever is more appropriate, was used to determine association between socio-demographic characteristics and HIV treatment barriers. III. Results: There is a total of 116 respondents, 115 were males, homosexual (59.5%), with mean age of 30.25 years old (SD = 6.22) and majority (53.4%) were from NCR. The most common HIV treatment barriers reported by PLHIV in accessing treatment and care were unavailability of transportation and cost of courier services for ARV delivery (62.1%), location of treatment hubs (52.6%) and financial assistance (37.9%). IV. Conclusion: There is significant association between location of treatment hubs and respondents who finished college/graduate studies; checkpoints and crossing borders and: 1. respondents from Northern Luzon, 2. unemployment; financial assistance and: 1. Respondents 18 to 25 years old, 2. unemployment, 3. respondents who finished elementary/high school; psychosocial support and: 1. Respondents from NCR, 2. Respondents 26 to 30 years old;

Introduction: Differentiated service delivery (DSD) models for antiretroviral treatment (ART) for HIV are being scaled up in the expectation that they will improve the quality and efficiency of treatment delivery and reduce costs while maintaining at least equivalent clinical outcomes. Even this minimum requirement of equivalent clinical outcomes is poorly documented for most models and settings, however. We reviewed the recent literature on DSD models to describe what is known about clinical outcomes. Methods: We conducted a rapid systematic review of peer-reviewed publications in PubMed, Embase, and the Web of Science and major international conference abstracts that reported outcomes of DSD models for the provision of ART in sub-Saharan Africa from January 1, 2016 to September 12, 2019. Sources reporting standard clinical HIV treatment metrics, primarily retention in care and viral load suppression, were reviewed and categorized by DSD model and source quality assessed. Results and Discussion: Twenty-nine papers and abstracts describing 37 DSD models and reporting 52 discrete outcomes met search inclusion criteria. Of the 37 models, 7 (19%) were facility-based individual models, 12 (32%) out-of-facility based individual models, 5 (14%) client-led groups, and 13 (35%) healthcare worker-led groups. Retention was reported for 73% of the models and viral suppression for 57%. Where a comparison with conventional care was provided, retention in most DSD models was within 5% of that for conventional care; where no comparison was provided, retention generally exceeded 80%. For viral suppression, all those with a comparison to conventional care reported a small increase in suppression in the DSD model; reported suppression exceeded 90% in 11/21 models. Analysis was limited by the extensive heterogeneity of study designs, outcomes, models, and populations. Most sources did not provide comparisons with conventional care, and metrics for assessing outcomes varied widely and were in many cases poorly defined. Conclusion: Existing evidence on the clinical outcomes of DSD models for HIV treatment in sub-Saharan Africa is limited in both quantity and quality but suggests that retention in care and viral suppression are roughly equivalent to those in conventional models of care.

Long-acting (LA) drug-delivery system (DDS) successes are linked to their abilities to harness biocompatible polymers and materials for sustained and predictable release of therapeutic agents over an extended period of time. For human immune deficiency virus type one (HIV-1) infections, LA DDSs hold great promise in closing the gaps of daily oral therapy for treatment and prevention. Examples are Cabenuva, Apretude and Sunlenca, which have been shown to be safe and effective. Alternative promising drug delivery technologies such as implants, prodrugs, vaginal rings, and microarray patches are being explored to further meet patients’ needs. We posit that improved physicochemical properties of the formulation payloads and material chemistry design with optimal drug release kinetics holds the potential to optimize release profiles. Furthermore, for the treatment and prevention of HIV-1 infection, the landscape of LA medicines now in clinical or preclinical development offers hope that the strategic design of polymers will further improve upon controlled delivery of drugs to simplify dosing schedules.

A multiscale mathematical model is proposed seeking to study the propagation dynamics of the Human Immunodeficiency Virus (HIV) in a group of young people between 15 and 24 years of age, through sexual contact without protection, considering the use of antiretroviral therapy (ART) and therapeutic failure. The model consists in a scale-free complex network that follows a power law, coupled with the immunological dynamics of each individual, that is, it considers the infection by the virus in the immune system of each HIV carrier, through a system of non-linear differential equations that govern the infection’s behavior in the immune system. Propagation of the virus in the network is modelled by taking into account information from the immunological status of each person. The study found that for a population to have high HIV prevalence, it is not necessary at the beginning of the simulation time for the virus to propagate rapidly. In addition, the study proves that with a higher number of sexual partners, there will be greater prevalence of HIV in the population and that the use of ART helps to control the propagation of the infection in the population. As an interesting result, it was also found that there is a higher number of HIV carriers who abandon ART than those who have access to it.

Immune reconstitution inflammatory syndrome (IRIS) presents as an exaggerated immune reaction that occurs during dysregulated immune restoration in immunocompromised patients in late-stage HIV infection who commenced antiretroviral treatments. Virtually, any opportunistic pathogen can provoke this type of immune restoration disorders. In this review, we focus on recent development in the identification of risk factors for Cryptococcal IRIS and on advancements in our understanding of C-IRIS immunopathogenesis. We overview new findings in blood and cerebrospinal fluid which can potentially be useful in the diagnosis of cryptococcal meningitis IRIS. We assess the utility of these biomarkers to identify putative host-based targets, which may justify a clinical need for improvement in monitoring a patient’s laboratory results and adjusting treatment modalities in AIDS patients co-infected with Cryptococcus.

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from the patients’ bodies. A potential strategy called “lock-in apoptosis” targeting the budding phase of life cycle of virus leading to susceptibility to apoptosis of HIV-1 infected cells for elimination of HIV-1 reservoirs and ultimately for a complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA) approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.