Analytical Treatment Interruption (ATI) to Assess the Immune System's Ability to Control HIV in Participants Who Became HIV-infected During the HVTN 704/HPTN 085 AMP Study

NCT04801758 | Completed Results DMC

• 2 other identifiers: HVTN 804/HPTN 095UM1AI068614
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 6

Brief Summary

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.

Conditions

HIV Infection

Keywords

HIV; Antibody; LTNPs; ECs; VCs; Treatment interruption

Outcome Measures

Primary Outcomes (6)

• 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

  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

  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

  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).

  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.

  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.

  Measured through participant's last study visit, up to 18 months

Secondary Outcomes (9)

• Cumulative Incidence of Participants With First Viral Load ≥ 200 Copies/mL at Week 8, 16, and 24 of Schedule 1: Monitoring ATI

  Measured for participants undergoing ATI up at week 8, 16, and 24

• Response Rate of HIV-specific CD4+ and CD8+ T-cells

  Measured through participant's last study visit, on average 15 months

• Magnitude of HIV-specific CD4+ and CD8+ T-cells

  Measured through participant's last study visit, on average 15 months

• Polyfunctionality of HIV-specific CD4+ and CD8+ T-cells

  Measured through participant's last study visit, on average 15 months

• Magnitude of Neutralizing Antibodies (nAb) Responses Against Autologous and Heterologous HIV Isolates

  Measured through participant's last study visit, on average 15 months

Study Arms (1)

Analytical Treatment Interruption

EXPERIMENTAL

Participants who received VRC01 or placebo and got HIV while enrolled in HVTN 704/HPTN 085 (NCT02716675).

Other: Analytical Treatment Interruption

Interventions

Analytical Treatment Interruption OTHER

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".

Analytical Treatment Interruption

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Estimated date of HIV-1 acquisition within 8 weeks of participant's last HVTN 704/HPTN 085 infusion.
• Initiated ART within 28 weeks of HVTN 704/HPTN 085 HIV-1 date of diagnosis.
• Receiving continuous ART for at least 1 year. ART interruptions of up to 7 days and ≥ 90 days prior to enrollment are acceptable. Within- and between-class changes in ART within the previous year are acceptable.
• If on an NNRTI, willingness and ability to switch to a PI- or INSTI-containing regimen for at least 4 weeks prior to ART interruption.
• Willingness to interrupt ART for up to 24 weeks or up to the time of meeting ART re-initiation criteria.
• Willingness to re-initiate ART upon meeting study ART re-initiation criteria.
• Willingness to use barrier protection (ie, male or female condoms) for all sexual activity until after confirmation of viral suppression following ART re-initiation.
• Willingness for CRS staff to contact primary HIV care provider to exchange information regarding HVTN 804/HPTN 095 and participant medical history.
• Site investigator anticipates that a fully active alternative ART regimen could be constructed and would be available in the event of virologic failure on the participant's current ART regimen.
• Access to a participating CRS and willingness to adhere to study visit schedule and to be followed for the planned duration of the study.
• Ability and willingness to provide informed consent.
• Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to enrollment with verbal demonstration of understanding of all questionnaire items answered incorrectly.
• Agrees not to enroll in another study of an investigational research agent for the duration of the participant's trial participation.
• Immunology/Virology
• HIV-1 infection, with reactive HIV-1 antibody and any Multispot or Geenius HIV-1/HIV-2 results, documented by the HVTN 704/HPTN 085 HIV diagnostic algorithm.

You may not qualify if:

• Any plasma HIV-1 RNA ≥ LLOQ (LLOQ: 75, 50, 40, or 20 copies/mL) within 12 months prior to enrollment.
• NOTE: Two "blips" (ie, plasma HIV-1 RNA \> LLOQ) \< 400 copies/mL are allowed if preceded and followed by values \< LLOQ and if the blips occur more than 6 months prior to enrollment.
• Note: US volunteers must have results from a CLIA or VQA-approved assay. Non-US sites must have results from locally available assays that are approved as standard-of-care by their regional governing bodies.
• History of AIDS-defining illnesses or US Centers for Disease Control (CDC) Category C events per the current list on the CDC website (see HVTN 804/HPTN 095 SSP).
• Autoimmune disease, including Type I diabetes mellitus (Not excluded from participation: Volunteer with mild, stable and uncomplicated autoimmune disease that does not require consistent immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate AE assessments).
• Blood products received within 120 days before planned ART interruption.
• HIV or non-HIV experimental vaccine(s) received within the last 1 year. Exceptions may be made by the HVTN 804/HPTN 095 PSRT for vaccines that have subsequently undergone licensure by the FDA or by the national regulatory authority where the volunteer is enrolling. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 804/HPTN 095 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 1 year ago, eligibility for enrollment will be determined by the HVTN 804/HPTN 095 PSRT on a case-by-case basis.
• Licensed live attenuated vaccines received within 30 days before planned ART interruption (eg, measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever; live attenuated influenza vaccine).
• Licensed vaccines that are not live attenuated vaccines received within 14 days before planned ART interruption (eg, tetanus, pneumococcal, hepatitis A or B).
• Receipt of any emergency-use authorized, WHO emergency use listed, licensed or registered SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccine within 4 weeks before planned ART interruption. Note: SARS-CoV-2 vaccination is not required for HVTN 804/HPTN 095 eligibility.
• Significant or unstable cardiac or cerebrovascular disease (eg, angina, congestive heart failure \[CHF\], recent cerebrovascular accident \[CVA\], or myocardial infarction \[MI\]).
• Volunteers who have:
• a SARS-CoV-2 positive test (direct viral detection, eg, viral nucleic acid or antigen detection) ≤14 days of enrollment, if asymptomatic OR
• unresolved COVID-19 (ie, SARS-CoV-2 positive test AND symptoms) ≤ 14 days of enrollment (not excluded: individuals with symptoms consistent with residual sequelae of resolved COVID19, in the clinical judgement of the investigator)
• Pregnant or breastfeeding

Sponsors & Collaborators

• HIV Vaccine Trials Network: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• HIV Prevention Trials Network: collaborator
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator

Study Sites (6)

Instituto de Pesquisa Clinica Evandro Chagas (IPEC), FIOCRUZ

Rio de Janeiro, 21040-360, Brazil

Location

Asociacion Civil Selva Amazonica (ACSA), Iquitos CRS

Iquitos, Maynas, 1, Peru

Location

Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales, San Marcos CRS

Callao, 15081, Peru

Location

Asociacion Civil Impacta Salud y Educacion, Barranco CRS

Lima, 04-15063, Peru

Location

Via Libra CRS

Lima, 15001, Peru

Location

San Miguel CRS

Lima, 32-15088, Peru

Location

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
• Organization: Fred Hutchinson Cancer Research Center

jandries@fredhutch.org

206-667-5812

Study Officials

• Shelly Karuna

  HVTN Core, Fred Hutch

  STUDY CHAIR

• Katharine Bar

  University of Pennsylvania

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: March 17, 2021
• Study Start: August 22, 2022
• Primary Completion: July 22, 2024
• Study Completion: July 22, 2024
• Last Updated: April 20, 2025
• Results First Posted: April 20, 2025

Record last verified: 2025-04

Locations

BR (1); PE (5)