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:
Participant gender:
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
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