The study was done to: * Start antiretroviral therapy (ART) early in those recently or acutely infected with HIV-1 * See how starting ART as soon as the infection is found affects the amount of HIV-1 in blood and how well the body fights the HIV-1 infection * Look at the amount of HIV-1 DNA (genetic material for HIV-1) seen in CD4+ T-cells (infection-fighting cells in blood) after 48 weeks of ART * See how early treatment for HIV affects the numbers of HIV-1 infection fighting cells (CD4+ and CD8+ T-cells) in blood
This was a Phase II, prospective, open-label two-step study to measure the effects of early ART on the establishment of HIV-1 reservoir and HIV-1-specific immunity. Participants were enrolled if they fulfilled the inclusion criteria for acute HIV-1 infection (AHI) diagnosis within 7 days prior to entry and had an enrollment visit with the immediate initiation of ART. Plasma and serum samples for Fiebig staging were collected at the time of ART initiation. Participants were followed for up to 216 weeks (72 weeks on Step 1 and 144 weeks on Step 2). Evaluations at weeks 2 and 8 on Step 1 were performed via telephone. The Fiebig stage-classification system was used to characterize the progression from HIV-1 exposure to HIV-1 seroconversion at the time of ART initiation. In this study, the five Fiebig stages of interest were simplified into three study groups as described below (based on HIV-1 antibody diagnostic profile at time of ART initiation). The primary analysis was based on Step 1. Step 2 was added to the study for long term follow-up. The rationale for the extended follow-up period was to expand the number of available participants for future therapeutic and cure studies without the burden of frequent visits and the cost of study-provided laboratory testing. 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 (WB) or Geenius HIV-1/HIV-2) Group 3: Fiebig V (reactive HIV-1 antibody and positive WB or Geenius HIV-1/HIV-2 without p31 band) Although participants in Fiebig VI (positive WB or Geenius HIV-1/HIV-2 with p31 band) were not specifically targeted for enrollment in this study, it was possible that a small number of participants would 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. Participants who were determined to be in Fiebig VI were followed on the study for no more than 24 weeks on Step 1, allowing ample time for them to pursue alternative sources for ART. Enrolled participants without HIV or in Fiebig VI were replaced. The study-provided regimen was single tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Other non-study-provided antiretroviral (ARV) regimens were also allowed for participants who were pregnant, breastfeeding, or unable/unwilling to take EVG/COBI/FTC/TAF or BIC/FTC/TAF, or for participants whose local health care/primary care provider preferred starting a different initial ARV regimen.
Participants received one tablet of elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg by mouth daily with food or one tablet of bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg by mouth daily with or without food. Other non-study-provided ARV regimens were allowed for participants who were pregnant, breastfeeding, or unable/unwilling to take EVG/COBI/FTC/TAF or BIC/FTC/TAF, or for participants whose local health care/primary care provider preferred starting a different initial ARV regimen.
Proportion of Participants With Undetectable Cell-associated HIV-1 DNA (CAHD)
Proportion of participants with 0 copies of CAHD per 5 million CD4+ blood-derived CD4+ T-cells (assayed by quantitative polymerase chain reaction \[qPCR\]), assessed separately and jointly by integrase and gag assays. In order for a participant to be considered as having 0 copies of CAHD for joint assays, the participant must be found to have an undetectable CAHD result from both integrase and gag assays. If all participants in both arms had undetectable CAHD then the statistical test was not performed.
Time frame: At week 48
HIV-1-specific CD4+ and T-cell Responses to Nef, Gag, Pol and Env by Flow Cytometry
Percent of HIV-1-specific CD4+ T-cells expressing any cytokine/marker (CD40L, CD107a, IFNg, MIP1B, TNFa) to each of the 4 protein stimulants (nef, gag, pol and env) by flow cytometry while HIV-1 RNA is suppressed on ART. The results for a specific participant are calculated by subtracting the corresponding background control value (media control). If the result would be less than zero after background subtraction, the result was set to zero. Cytokine/Marker Names: CD40 ligand (CD40L); Cluster of Differentiation 107a (CD107a); Interferon gamma (IFNg); Macrophage Inflammatory Protein beta (MIP1B); Tumor Necrosis Factor alpha (TNFa)
Time frame: At week 48
HIV-1-specific CD8+ and T-cell Responses to Nef, Gag, Pol and Env by Flow Cytometry
Percent of HIV-1-specific CD8+ T-cells expressing any cytokine/marker (CD40L, CD107a, IFNg, MIP1B, TNFa) to each of the 4 protein stimulants (nef, gag, pol and env) by flow cytometry while HIV-1 RNA is suppressed on ART. The results for a specific participant are calculated by subtracting the corresponding background control value (media control). If the result would be less than zero after background subtraction, the result was set to zero. Cytokine/Marker Names: CD40 ligand (CD40L); Cluster of Differentiation 107a (CD107a); Interferon gamma (IFNg); Macrophage Inflammatory Protein beta (MIP1B); Tumor Necrosis Factor alpha (TNFa)
Time frame: At 48 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
195
31788 Alabama CRS
Birmingham, Alabama, United States
Ucsd, Avrc Crs (701)
San Diego, California, United States
Harbor-UCLA Med. Ctr. CRS (603)
Torrance, California, United States
Whitman Walker Health CRS (31791)
Washington D.C., District of Columbia, United States
The Ponce de Leon Center CRS (5802)
Atlanta, Georgia, United States
Northwestern University CRS (2701)
Chicago, Illinois, United States
Rush Univ. Med. Ctr. ACTG CRS (2702)
Chicago, Illinois, United States
Massachusetts General Hospital ACTG CRS (101)
Boston, Massachusetts, United States
Brigham and Women's Hosp. ACTG CRS (107)
Boston, Massachusetts, United States
Washington University CRS (2101)
St Louis, Missouri, United States
...and 20 more locations
Proportion of Participants With Undetectable Cell-associated HIV-1 DNA (CAHD) Prior to ART Initiation
Proportion of participants with 0 copies of CAHD per million CD4+ blood-derived CD4+ T-cells (assayed by quantitative PCR \[qPCR\]), assessed separately and jointly by integrase and gag assays. In order for a participant to be considered as having 0 copies of CAHD for joint assays, the participant must be found to have an undetectable CAHD result from both integrase and gag assays. If all participants in both arms had undetectable CAHD then the statistical test was not performed.
Time frame: At week 0