The purpose of this study is to learn whether having the AMP Study antibody (called VRC01) in a person's body might help their immune system control HIV better, even without HIV medication called antiretroviral therapy or ART, if they get HIV. This study will evaluate the viral and immune system responses in an Analytical Treatment Interruption (ATI), in participants who received VRC01 or placebo and got HIV while enrolled in HVTN 704/HPTN 085 (NCT02716675). Participants in this study will stop taking their HIV medication. They will stay off HIV medication unless and until the HIV levels in their blood show that their immune system is unable to control the HIV or they meet other ART re-start criteria as noted in section "Detailed Description". While they are not taking HIV medication, their HIV levels will be tested frequently, and their health will be monitored closely. This is called an analytical treatment interruption, or an ATI. An ATI is an experimental procedure that is only used in carefully monitored research.
The purpose of this study is to evaluate immunologic and virologic responses in an Analytical Treatment Interruption (ATI), in participants who received VRC01 or placebo and got HIV while enrolled in the HVTN 704/HPTN 085 Antibody-Mediated Prevention (AMP) Study (NCT02716675). ATI begins with the cessation of ART on Schedule 1 (Monitoring ATI). Participants on Schedule 1 will attend study visits every week for the first 8 weeks and at least every 2 weeks for the next 16 weeks. After that, participants will attend study visits once a month for the next 6 months, if their body is controlling their HIV without ART. Participants on Schedule 1 for more than a year will have visits every 3 months. For participants on Schedule 1 (Monitoring ATI), a confirmed VL ≥ 200 copies/mL will trigger transition to Schedule 2 (ATI monitoring with viremia). Participants on Schedule 2 will attend study visits every week for the first 8 weeks and at least every 2 weeks for the next 28 weeks. After that, participants will attend study visits once a month for the next 4 months, if their body is controlling their HIV without ART. Participants on Schedule 2 for more than a year will have visits every 3 months. For participants on Schedule 1 (Monitoring ATI), any of the following non-virologic criteria will trigger re-initiation of ART and transition to Schedule 3 (Follow-up on ART) : confirmed CD4+ T-cell count \< 350 cells/mm3, any HIV-related syndrome, pregnancy or breastfeeding, or ART re-initiation requested by participant or if deemed medically necessary by primary HIV provider or clinical research site Investigator of Record. Participants on Schedule 3 will attend study visits every 2 weeks for the first 12 weeks, once a month for the next 16 weeks, and on 2 occasions 3 months apart for the next 24 weeks. For participants on Schedule 2 (ATI monitoring with viremia), the following virologic criteria will trigger re-initiation of ART and transition to Schedule 3 (Follow-up on ART): viral load remains ≥ 1,000 copies/mL for ≥ 4 consecutive weeks AND viral load has not dropped 0.5 log from the previous week (Week 0 - Week 24), confirmed viral load ≥ 200 copies/mL (after Week 24). Or, the following non-virologic criteria will trigger re-initiation of ART and transition from Schedule 2 (ATI monitoring with viremia) to Schedule 3 (Follow-up on ART): confirmed CD4+ T-cell count \< 350 cells/mm3, any HIV-related syndrome, pregnancy or breastfeeding, or ART re-initiation requested by participant or if deemed medically necessary by primary HIV provider or clinical research site Investigator of Record. Study duration is potentially indefinite for participants maintaining extreme and extended viral control during ATI. Study duration for most participants is expected to be 13-18 months. The maximum anticipated duration for any participant is expected to be approximately 2 1/2 to 3 years. Visits may include medical history review, physical exam, HIV testing, other STI testing (blood, urine, and rectal and oral swab collection), blood draws, pregnancy testing for participants assigned female sex at birth that can become pregnant, HIV transmission risk reduction counseling, and interviews/questionnaires.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
18
Participants will stop taking their HIV medication and will stay off HIV medication unless and until the HIV levels in their blood show that their immune system is not controlling their HIV or they meet other ART re-start criteria as noted in section "Detailed Description".
Instituto de Pesquisa Clinica Evandro Chagas (IPEC), FIOCRUZ
Rio de Janeiro, Brazil
Asociacion Civil Selva Amazonica (ACSA), Iquitos CRS
Iquitos, Maynas, Peru
Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales, San Marcos CRS
Callao, Peru
Asociacion Civil Impacta Salud y Educacion, Barranco CRS
Lima, Peru
Via Libra CRS
Lima, Peru
San Miguel CRS
Lima, Peru
Time to Meeting Criteria for ART Re-initiation
From ART Re-Initiation Criteria form, calculated median and range of weeks of ATI meeting ART re-initiation criteria by HVTN 704/HPTN 085 treatment assignment. Note that participants with plasma ARV levels consistent with ongoing ARV use during ATI schedule are excluded
Time frame: Measured through participant's last visit on Schedule 1 or 2, up to 6 months.
Frequency of Sustained Post-treatment HIV Control, Defined as ≥ 24 Weeks Off ART Without Meeting ART Re-initiation Criteria
From ART Re-Initiation Criteria form, counts number of participants with ≥ 24 weeks of ART without meeting ART re-initiation criteria by HVTN 704/HPTN 085 treatment assignment. Note that participants with evidence of ARV use in ATI monitoring schedule are excluded from the analysis
Time frame: Measured at week 24 of schedule 1- monitoring ATI
Percentage of Participants Who Experience Adverse Events (AEs)
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Time frame: Measured through participant's last study visit, up to 18 months.
Number of Participants Reporting Serious Adverse Events (SAEs)
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 (exceptions apply).
Time frame: Measured through participant's last study visit, up to 18 months.
Number of Participants Who Discontinue ATI
Tabulated by reason and HVTN 704/HPTN 085 treatment group. Note that 1. Participants with plasma ARV levels consistent with ongoing ARV use during ATI schedule are excluded; 2. Participants may meet more than one ART re-initiation criterion.
Time frame: Measured through participant's last visit on Schedule 1 or 2, up to 6 months
Number of Local Laboratory Values Meeting Grade 2 AE Criteria or Above
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.
Time frame: Measured through participant's last study visit, up to 18 months
Cumulative Incidence of Participants With First Viral Load ≥ 200 Copies/mL at Week 8, 16, and 24 of Schedule 1: Monitoring ATI
The number (percentage) of participants with first viral load \>= 200 by Schedule 1 week 8, 16, and 24. Participants with plasma ARV levels consistent with ongoing ARV use during ATI schedule are excluded
Time frame: Measured for participants undergoing ATI up at week 8, 16, and 24
Response Rate of HIV-specific CD4+ and CD8+ T-cells
Measured by flow cytometry
Time frame: Measured through participant's last study visit, on average 15 months
Magnitude of HIV-specific CD4+ and CD8+ T-cells
Measured by flow cytometry
Time frame: Measured through participant's last study visit, on average 15 months
Polyfunctionality of HIV-specific CD4+ and CD8+ T-cells
Measured by flow cytometry
Time frame: Measured through participant's last study visit, on average 15 months
Magnitude of Neutralizing Antibodies (nAb) Responses Against Autologous and Heterologous HIV Isolates
Measured by TZM-bl neutralization assay
Time frame: Measured through participant's last study visit, on average 15 months
Non-neutralizing, FcγR-mediated Antibody Effector Functions
Measured by ADCC, ADCP, and virion capture
Time frame: Measured through participant's last study visit, on average 15 months
Frequency of Dendritic Cell Activation and Maturation Markers
Measured by flow cytometry or other cell phenotyping assays
Time frame: Measured through participant's last study visit, on average 15 months
Frequency of T- and B-cell Activation and Exhaustion Markers
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Measured by flow cytometry or other cell phenotyping assays
Time frame: Measured through participant's last study visit, on average 15 months
Frequency of CD4+ T Cells Carrying Intact and/or Total Pro-viral HIV DNA, Replication Competent Virus, and/or Cell-associated HIV RNA
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.
Time frame: Measured through participant's last study visit, on average 15 months