Modulating the Impact of Critical Events in Early HIV Infection: Effect of ART Initiation and Alcohol Use

• Status: Completed
• Trial end date: 2020-11-30
• Target enrollment: 0
• Participant gender: Male

Summary

The overall objective is to determine the influence of timing of ART initiation and alcohol consumption on HIV disease course, including detailed analysis of important events occurring shortly after HIV acquisition. ART initiation immediately after HIV infection (during Fiebig stages I-II) largely results in smaller HIV reservoir and lower HIV-associated systemic inflammation, which has been linked to non-AIDS morbidity and mortality. Immediate ART also reduces HIV-associated bacterial translocation and may prevent dysbiosis, an alteration of the intestinal microbiota that has been linked to increased systemic inflammation. Immediate intervention is not, however, generally feasible and more information is required about the consequences of starting ART at later time-points, but still early after acquisition. The proposed study will be conducted in Lima, Peru, in the cohort of 180 MSM with acute (Ab-, HIV RNA+) or recent (≤ 3 months) HIV infection. Alcohol use disorder is present in ~50% of HIV-infected MSM in our cohort, which is four times higher than that seen among males in the general Peruvian population. Although the role of alcohol use in HIV pathogenesis and disease course remains unclear, some studies show a correlation with accelerated disease progression. In animal models and clinical studies, both acute and chronic alcohol consumption have been linked to bacterial translocation and activation of the innate immune system, which can lead to increases in pro-inflammatory cytokines. The effects of alcohol resemble early post-infection changes in bacterial translocation and pro-inflammatory cytokines induced by HIV and their impact on HIV disease course before and after ART initiation remain unexplored.

Specific Aim 1: To determine the relative long-term benefits of immediate vs. early vs. delayed ART initiation. The investigators will study outcomes after 2 and 4 years in MSM diagnosed with acute or recent HIV infection. The investigators will examine outcomes in 3 groups based on time of ART initiation: a) immediate: during FI-II (N~30), b) early: during FIII-V (N~50) or c) delayed: at 24 weeks after diagnosis (N~80). The investigators anticipate that CD4+ T cell counts and peripheral inflammatory markers in the FIII-V group and the delayed group will approach those in the immediate treatment group (FI-II) over time; in contrast, they expect that those started ART at "early" or "delayed" time points will have persistent changes in the GI microbiome and in the HIV reservoir.

Specific Aim 2: To determine the impact of alcohol use on the relative long-term benefits of immediate vs. early vs. delayed initiation of ART. The investigators will examine the impact of alcohol use on critical events in HIV infection. They hypothesize that dose-dependent alcohol-induced changes will compound the negative effects of HIV and lead to greater levels of dysbiosis and inflammation, higher early plasma HIV RNA, and greater "seeding" and persistence of HIV DNA in participants with high-level alcohol use. The investigators will assess viral load, GI microbiome and metagenomics, pro-inflammatory cytokines, production of msRNA and analyze the impact on alcohol use in all subjects prior to ART initiation and among ART-adherent participants with persistent viral suppression.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Fred Hutchinson Cancer Research Center
• Collaborators: Asociación Civil Impacta Salud y Educación, Peru; National Institute on Drug Abuse (NIDA); Seattle Children's Hospital; Université de Montréal; University of California, San Francisco; University of Washington

Criteria

Inclusion Criteria:

• Men who have sex with men or transgender women HIV-infected with prior participation in SABES study in Lima Peru OR Established HIV infection OR HIV uninfected

Exclusion Criteria:

• counter-indication for use of study antiretroviral drugs