This is a phase II, prospective, open-label study to measure the effects of early antiretroviral therapy (ART) on the establishment of HIV-1 reservoir and HIV-1-specific immunity.  Participants with acute HIV-1 infection (AHI) will have an enrollment visit that will include the immediate initiation of ART. The primary endpoint is cell-associated HIV-1 DNA (CAHD) in 5 million blood-derived CD4+ T-cells assayed by quantitative PCR (qPCR) at week 48.

Participants who demonstrate no detectable CAHD in 5 million blood-derived CD4+ T- cells at week 48 and a comparative subset of participants who have detectable CAHD will be offered and consented for optional leukapheresis or large volume blood collection, cerebrospinal fluid collection via lumbar puncture, and gut biopsy via flexible sigmoidoscopy. Participants may agree to one or more of these optional procedures, which will be performed at any time from week 60 to week 72 in willing participants.

The Fiebig stage-classification system will be used to characterize the progression from HIV-1 exposure to HIV-1 seroconversion at the time of ART initiation. Plasma and serum samples will be collected at the time of ART initiation and the results of the Fiebig stage at ART initiation will be available within 12 weeks. In this study, the Fiebig I-V stages of interest will be simplified into three study groups (based on HIV-1 antibody diagnostic profile at the time of ART initiation) as described below.

Group 1:    Fiebig I/II (non-reactive HIV-1 antibody)

Group 2:    Fiebig III/IV (reactive HIV-1 antibody and negative or indeterminate results on the Western blot or Geenius HIV-1/HIV-2)

Group 3:    Fiebig V (reactive HIV-1 antibody and positive Western blot or Geenius HIV-1/HIV-2 without p31 band)

It is possible that a small number of participants will be determined to be in Fiebig VI (positive Western blot or Geenius HIV-1/HIV-2 with p31 band) based on analysis of the entry samples even though these participants are not specifically targeted for enrollment in this study. Participants who are determined to be in Fiebig VI will be followed until study week 24, allowing ample time for them to pursue alternative sources for ART.

The Clinical Management Committee of the A5354 protocol team will review the Fiebig staging and primary endpoint determinations and ensure that these results are communicated to the site, as described in the study’s Manual of Procedures.

DURATION                 Up to 72 weeks

SAMPLE SIZE            A total of 150 participants will be enrolled (50 in each study group). Up to 25 eligible participants will be asked to consent to each optional procedure.

POPULATION            Men and women 18 years and older with AHI.

NOTE: Pregnant and breastfeeding women may enroll in the study.

REGIMEN                   The antiretroviral (ARV) regimen provided through the study is the single tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF). Other non-study-provided ARV regimens will be allowed for participants who are pregnant, breastfeeding, or unable/unwilling to take EVG/COBI/FTC/TAF, or for participants whose local health care/primary care provider prefers starting a different initial ARV regimen.