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Background Prior to the widespread availability of antiretroviral therapy (ART), men living with human immunodeficiency virus (HIV) with urethritis had increased concentrations of HIV in semen. This study aims to better evaluate HIV shedding in men with urethritis receiving ART, and its implications for the cure of HIV. Methods Men living with HIV with urethritis taking ART ≥12 weeks were enrolled at a sexually transmitted infections clinic in Lilongwe, Malawi. Study follow-up included visits at 1, 2, 4, 8, 12, 24, 36, and 48 weeks after urethritis diagnosis and treatment. Matched blood and semen samples were collected at all visits, and all additional episodes of urethritis were followed with extra visits 1, 2, and 4 weeks after treatment. Results There were 111 men enrolled in the study between January 2017–March 2019, and 77 (69%) were suppressed in the blood (<400 copies/mL). Among the 77 men, 87 episodes of urethritis were evaluated during follow-up. Of the 87 episodes, 15 episodes (17%) had instances of seminal viral shedding ≥400 copies/mL despite viral suppression in the blood. During nonurethritis follow-up, ≤6% of men at each visit had a viral load ≥400 copies/mL in the semen while maintaining viral suppression in the blood. Conclusions An HIV cure requires the elimination of HIV from every body compartment, but available ART does not currently accomplish this. Our study highlights the male genital tract as a local source of HIV that can be reversibly activated. A better understanding of this phenomenon is important to advance the HIV cure field. [ABSTRACT FROM AUTHOR]

Background People with advanced human immunodeficiency virus (HIV) (CD4 < 50) remain at high risk of tuberculosis (TB) or death despite the initiation of antiretroviral therapy (ART). We aimed to identify immunological profiles that were most predictive of incident TB disease and death. Methods The REMEMBER randomized clinical trial enrolled 850 participants with HIV (CD4 < 50 cells/µL) at ART initiation to receive either empiric TB treatment or isoniazid preventive therapy (IPT). A case-cohort study (n = 257) stratified by country and treatment arm was performed. Cases were defined as incident TB or all-cause death within 48 weeks after ART initiation. Using multiplexed immunoassay panels and ELISA, 26 biomarkers were assessed in plasma. Results In total, 52 (6.1%) of 850 participants developed TB; 47 (5.5%) died (13 of whom had antecedent TB). Biomarkers associated with incident TB overlapped with those associated with death (interleukin [IL]-1β, IL-6). Biomarker levels declined over time in individuals with incident TB while remaining persistently elevated in those who died. Dividing the cohort into development and validation sets, the final model of 6 biomarkers (CXCL10, IL-1β, IL-10, sCD14, tumor necrosis factor [TNF]-α, and TNF-β) achieved a sensitivity of 0.90 (95% confidence interval [CI]:.87–.94) and a specificity of 0.71(95% CI:.68–.75) with an area under the curve (AUC) of 0.81 (95% CI:.78–.83) for incident TB. Conclusion Among people with advanced HIV, a parsimonious inflammatory biomarker signature predicted those at highest risk for developing TB despite initiation of ART and TB preventive therapies. The signature may be a promising stratification tool to select patients who may benefit from increased monitoring and novel interventions. Clinical Trials Registration NCT01380080 [ABSTRACT FROM AUTHOR]