Trial Outcomes & Findings for Analytical Treatment Interruption (ATI) to Assess the Immune System's Ability to Control HIV in Participants Who Became HIV-infected During the HVTN 703/HPTN 081 AMP Study (NCT NCT04860323)

Analytical Treatment Interruption (ATI) to Assess the Immune System's Ability to Control HIV in Participants Who Became HIV-infected During the HVTN 703/HPTN 081 AMP Study

From ART Re-Initiation Criteria form, calculated median and range of weeks of ATI meeting ART re-initiation criteria by HVTN 703/HPTN 081 treatment assignment. Note that participants with evidence of ARV use during ATI schedule are excluded

From ART Re-Initiation Criteria form, counts number of participants with ≥ 24 weeks of ART without meeting ART re-initiation criteria by HVTN 703/HPTN 081 treatment assignment. Note that participants with evidence of ARV use in ATI monitoring schedule are excluded from the analysis

Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

Tabulated by reason and HVTN 703/HPTN 081 treatment group. Note that 1. participants (N= 2) with evidence of ARV use during ATI schedule are excluded; 2. Participants may meet more than one ART re-initiation criterion.

The number (percentage) of participants with lab grade \> 1 for alanine aminotransferase (ALT), Estimated Glomerular Filtration Rate (eFGR), Absolute Neutrophil Count, Direct Bilirubin, Hemoglobin, Platelets was summarized by arm. Only measurements with at least 1 record of grade 2 AE or above were shown in the table.

The number (percentage) of participants with first viral load \>= 200 by Schedule 1 week 8, 16, and 24. 2 Participants from VRC01 10mg/kg group with evidence of ARV use during ATI schedule are excluded. Given only 3 VRC01 10mg/kg participants followed ATI schedule, VRC01 treatment arms are grouped in this analysis.

The four entries in each table were the number of cells positive for IFN-γ and/or IL-2 for both the stimulated and the negative control data. If both negative control replicates were included, then the average number of total cells and the average number of positive cells were used. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the two individual peptide pool p-values considered, using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was ≤ 0.00001, the response to the peptide pool for the T-cell subset was considered positive. If at least one peptide pool for a specific HIV-1 protein was positive, then the overall response to the protein was considered positive.

PBMC samples were stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing cytokines (IFNy and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation.

NAb against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. Samples were processed using ART-Dex method to remove antiretrovirals in the specimens. An ART-resistant backbone was utilized to produce the viruses used for the study to further minimize potential virus inhibition by residual antiretrovirals. A titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). Net titer was then calculated by subtracting the MLV values, where the titer was set to 25 if it is less then MLV titer. For T/F and rebound autologous isolates, if participants with multiple isolates detected at each dilution and timepoints, geometric means titer was calculated.

Measured by ADCC

Measured by ADCP

Measured by virion capture

Peripheral blood mononuclear cells (PBMC) obtained as specified in AMP ATI protocols were used to examine the frequency of dendritic cells (DC) using a previously established DC high parameter flow cytometry panel that has been slightly modified to include Ki67, a marker of activation. This phenotyping was performed using PBMC that were thawed for the ICS assay for samples with sufficient cells for both ICS and phenotyping.

Measured by flow cytometry or other cell phenotyping assays

Measured by Intact Proviral DNA Assay (IPDA), Tat/rev Induced Limiting Dilution Assay (TILDA), assays detecting replication-competent virus-bearing cells, and/or measures of total proviral DNA. Cell-associated HIV-RNA may be quantitated as a measure of the transcriptionally active reservoir.