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Background HIV controllers (HICs) are a rare group of HIV-1-infected individuals able to naturally control viral replication. Several studies have identified the occurrence of HIV dual infections in seropositive individuals leading to disease progression. In HICs, however, dual infections with divergent outcomes in pathogenesis have been described. Case presentation Here, we present a case report of a HIC diagnosed in late 1999 who displayed stable CD4 + T cell levels and low plasmatic viral load across 12 years of follow-up. In early 2013, the patient started to present an increase in viral load, reaching a peak of 10,000 copies/ml in early 2014, followed by an oscillation of viremia at moderate levels in the following years. The genetic diversity of env proviral quasispecies from peripheral blood mononuclear cells (PBMCs) was studied by single genome amplification (SGA) at six timepoints across 2009–2017. Phylogenetic analyses of env sequences from 2009 and 2010 samples showed the presence of a single subtype B variant (called B 1 ). Analyses of sequences from 2011 and after revealed an additional subtype B variant (called B 2 ) and a subsequent dominance shift in the proviral quasispecies frequencies, with the B 2 variant becoming the most frequent from 2014 onwards. Latent syphilis related to unprotected sexual intercourse was diagnosed a year before the first detection of B 2, evidencing risk behavior and supporting the superinfection hypothesis. Immunologic analyses revealed an increase in CD8 + and CD4 + T cell immune activation following viremia increase and minor T cell subset alterations during follow-up. HIV-specific T cell responses remained low throughout the follow-up period. Conclusions Altogether, these results show that loss of viremia control in the HIC was associated with superinfection. These data alert to the negative consequences of reinfection on HIV pathogenesis, even in patients with a long history of viremia control and an absence of disease progression, reinforcing the need for continued use of adequate prevention strategies.

Pre-exposure prophylaxis (PrEP) prevents HIV infection among men who have sex with men (MSM) and transgender women (TGW) who are the groups that presents the high incidence risk in Brazil. This cross-sectional secondary analysis describes possible risk compensation, attitudes, and beliefs regarding the use of PrEP among 723 MSM and TGW evaluated in the PrEP Brazil study pre-screening phase. Possible risk compensation was reported by 31.6% individuals. In the multivariate model, factors that increased the likelihood of possible risk compensation were: self-referring as white vs. Black (AOR 2.05; CI 1.09, 3.85), perceiving high likelihood of getting HIV in next 12 months (AOR 1.78; CI 1.23, 2.56), being less afraid of HIV infection if using PrEP (AOR 1.93; CI 1.19, 3.14), feeling liberated to have more partners if using PrEP (AOR 2.93; CI 1.92, 4.49), and believing closest friends would use PrEP (AOR 2.51; CI 1.1, 5.71). We found that possible risk compensation was more common among individuals who presented high-risk perception for HIV infection, probably reflecting they feel at risk and could benefit from PrEP use.

Background:The antibody-mediated prevention (AMP) studies (HVTN 703/HPTN 081 and HVTN 704/HPTN 085) are harmonized phase 2b trials to assess HIV prevention efficacy and safety of intravenous infusion of anti-gp120 broadly neutralizing antibody VRC01. Antibodies for other indications can elicit infusion-related reactions (IRRs), often requiring premedication and limiting their application. We report on AMP study IRRs.Methods: From 2016 to 2018, 2699 HIV-uninfected, at-risk men and transgender adults in the Americas and Switzerland (704/085) and 1924 at-risk heterosexual women in sub-Saharan Africa (703/ 081) were randomized 1:1:1 to VRC01 10 mg/kg, 30 mg/kg, or placebo. Participants received infusions every 8 weeks (n = 10/ participant) over 72 weeks, with 104 weeks of follow-up. Safety assessments were conducted before and after infusion and at noninfusion visits. A total of 40,674 infusions were administered.Results: Forty-seven participants (1.7%) experienced 49 IRRs in 704/ 085; 93 (4.8%) experienced 111 IRRs in 703/081 (P , 0.001). IRRs occurred more frequently in VRC01 than placebo recipients in 703/081 (P , 0.001). IRRs were associated with atopic history (P = 0.046) and with younger age (P = 0.023) in 703/081. Four clinical phenotypes of IRRs were observed: urticaria, dyspnea, dyspnea with rash, and "other." Urticaria was most prevalent, occurring in 25 (0.9%) participants in 704/ 085 and 41 (2.1%) participants in 703/081. Most IRRs occurred with the initial infusion and incidence diminished through the last infusion. All reactions were managed successfully without sequelae.Conclusions: IRRs in the AMP studies were uncommon, typically mild or moderate, successfully managed at the research clinic, and resolved without sequelae. Analysis is ongoing to explore potential IRR mechanisms.

BACKGROUND Elite controllers (EC) are human immunodeficiency virus (HIV)-positive individuals who can maintain low viral loads for extended periods without antiretroviral therapy due to multifactorial and individual characteristics. Most have a small HIV-1 reservoir composed of identical proviral sequences maintained by clonal expansion of infected CD4 + T cells. However, some have a more diverse peripheral blood mononuclear cell (PBMC)-associated HIV-1 reservoir with unique sequences. OBJECTIVES To understand the turnover dynamics of the PBMC-associated viral quasispecies in ECs with relatively diverse circulating proviral reservoirs. METHODS We performed single genome amplification of the env gene at three time points during six years in two EC with high intra-host HIV DNA diversity. FINDINGS Both EC displayed quite diverse PBMCs-associated viral quasispecies (mean env diversity = 1.9-4.1%) across all time-points comprising both identical proviruses that are probably clonally expanded and unique proviruses with evidence of ongoing evolution. HIV-1 env glycosylation pattern suggests that ancestral and evolving proviruses may display different phenotypes of resistance to broadly neutralising antibodies consistent with persistent immune pressure. Evolving viruses may progressively replace the ancestral ones or may remain as minor variants in the circulating proviral population. MAIN CONCLUSIONS These findings support that the high intra-host HIV-1 diversity of some EC resulted from long-term persistence of archival proviruses combined with the continuous reservoir’s reseeding and low, but measurable, viral evolution despite undetectable viremia.

The analysis of the HIV-1 proviral dynamics after superinfection in the context of both natural and antiretroviral therapy (ART)-mediated suppression could yield unique insights into understanding the persistence of viral variants that seeded the infected cells at different times. In this study, we performed a longitudinal analysis of the env diversity of PBMC-associated HIV DNA quasispecies in two HIV controllers (EEC09 and VC32) that were superinfected with subtype F1 viruses several years after primoinfection with subtype B viruses. Patient EEC09 started ART soon after superinfection, while patient VC32 maintained a natural control of virus replication for at least six years following the superinfection. Our analysis revealed no significant temporal changes in the overall proportion of primo-infecting and superinfecting proviral variants over 2–3 years after superinfection in both HIV controllers. Upon the introduction of ART, individual EEC09 displayed no evidence of HIV-infected cell turnover or viral evolution, while subject VC32 displayed some level of HIV-infected cell reseeding and detectable evolution (divergence) of both viral variants. These results confirm that proviral variants that seeded the reservoir at different times throughout infection could persist for long periods under fully suppressive ART or natural viremic control, but the HIV-1 proviral dynamics could be different in both settings.