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.

The incidence of multidrug-resistant (MDR) bloodstream infections (BSI) is associated with high morbidity and mortality. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy in endemic regions. Novel diagnostic tests (RDTs) may facilitate and improve patient management. Data from patients with MDR GNB bacteremia at a university tertiary hospital were assessed over a 12-month period. 157 episodes of MDR GNB BSI were included in the study. Overall mortality rate was 50,3 percent. Rapid molecular diagnostic tests were used in 94% of BSI episodes. In univariate analysis, age (OR 1.05 (95% CI 1.03, 1.08) p<0.001), Charlson Comorbidity Index (OR 1.51 (95% CI 1.25, 1.83) p<0.001), Procalcitonin≥1(OR 3.67 (CI 95% 1.73, 7.79) p<0.001) and monotherapy with tigecycline (OR 3.64 (95% CI 1.13, 11.73) p=0.030) were the only factors associated with increased overall mortality. Surprisingly, time to appropriate antimicrobial treatment had no impact on mortality. MDR pathogen isolation, other than Klebsiella pneumoniae and Acinetobacter baumanii was associated with decreased mortality (OR 0.35 (95% CI 0.16, 0.79) p=0.011). In multivariate analysis though the only significant factor for mortality was Procalcitonin≥1(OR 2.84 (95% CI 1.13, 7.11) p=0.025). In conclusion, in an endemic area, mortality rates in MDR BSI remain high. High procalcitonin was the only variable that predicted death. The use of rapid diagnostics did not improve mortality rate.