HIV InfectionNCT04801758
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
A study testing Analytical Treatment Interruption in people with HIV Infection, run by HIV Vaccine Trials Network at 6 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HIV Infection
- What is being tested?
- Analytical Treatment Interruption
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 22 Aug 2022to 22 Jul 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Laboratory Inclusion Values:
- 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.
- Plasma HIV-1 RNA ≥ 1,000 copies/mL by any assay, prior to initiating ART.
- CD4+ cell count ≥ 450 cells/mm3 obtained within 90 days prior to enrollment.
- One plasma HIV-1 RNA below the lower limit of quantitation (LLOQ) of an VQA-certified or DAIDS-approved assay and collected:
- at screening, within 90 days prior to enrollment; and
- greater than 9 months prior to the screening HIV-1 RNA.
- Hematology
- Hemoglobin (Hgb) ≥ 10.0 g/dL for volunteers who were assigned female sex at birth, ≥ 11.0 g/dL for volunteers who were assigned male sex at birth.
- Absolute neutrophil count (ANC) ≥ 750 cells/mm3
- Platelets ≥ 100,000 cells/mm3
- Chemistry
- ALT < 2.5 times the institutional upper limit of normal and direct bilirubin within the institutional range of normal.
- Estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73m2
- Reproductive Status
- Volunteers capable of becoming pregnant: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed at the screening visit and prior to enrollment. Persons who are NOT capable of becoming pregnant due to having reached menopause (no menses for 1 year) or having undergone total hysterectomy or bilateral oophorectomy or tubal ligation (verified by medical records) are not required to undergo pregnancy testing.
- Reproductive status: A volunteer who is capable of becoming pregnant must agree to consistently use effective contraception for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through confirmation of viral suppression following ART re-initiation.
- Volunteers capable of becoming pregnant must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization, until after confirmation of viral suppression following ART re-initiation.
Who cannot join
- 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).
- Immunosuppressive medications received within 6 months before enrollment (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatologic condition; or [4] a single course of oral/parenteral prednisone or equivalent at doses < 60 mg/day and length of therapy < 11 days with completion at least 30 days prior to enrollment).
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- Blood products received within 120 days before planned ART interruption.
- Investigational research agents, other than experimental vaccine(s) (See Exclusion Criterion #7), received within 30 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]).
- Hepatitis B surface antigen (HBsAg) or positive HCV RNA (Not exclusionary: positive HCV Ab with negative HCV RNA).
- 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
- Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:
- A process that would affect the immune response;
- A process that would require medication that affects the immune response;
- Any contraindication to repeated blood draws, including inability to establish venous access;
- A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period; or
- Any condition specifically mentioned among the exclusion criteria.
- Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety, or a volunteer's ability to give informed consent.
- Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, could be exacerbated by events associated with protocol participation, which include: ATI, low-level viremia, subsequent viral rebound, and ART re-initiation.
- HIV dementia or other neurologic disease that, in the judgment of the investigator, would be a contraindication to study participation.
- Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
- Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's judgment, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study).
- Current untreated or incompletely treated active tuberculosis disease or current latent tuberculosis infection (Not excluded from participation: Volunteer who has latent tuberculosis infection and is undergoing treatment, with at least one month of treatment completed)
- Untreated or incompletely treated syphilis, gonorrhea, or chlamydia infection
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Peru5 sites
Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales, San Marcos CRS
Callao, 15081
Asociacion Civil Selva Amazonica (ACSA), Iquitos CRS
Iquitos, Maynas, 1
Asociacion Civil Impacta Salud y Educacion, Barranco CRS
Lima, 04-15063
Via Libra CRS
Lima, 15001
San Miguel CRS
Lima, 32-15088
Brazil1 site
Instituto de Pesquisa Clinica Evandro Chagas (IPEC), FIOCRUZ
Rio de Janeiro, 21040-360
About this study
Official title: Antiretroviral Analytical Treatment Interruption (ATI) to Assess Immunologic and Virologic Responses in Participants Who Received VRC01 or Placebo and Became HIV-infected During HVTN 704/HPTN 085
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.
Read the detailed description
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.
- Conditions
- HIV Infection
- Being tested
- Analytical Treatment Interruption
- Keywords
- HIV, Antibody, LTNPs, ECs, VCs, Treatment interruption
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Analytical Treatment InterruptionOther
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".
| Study group | Role | What they receive |
|---|---|---|
| Analytical Treatment Interruption | Experimental | Participants who received VRC01 or placebo and got HIV while enrolled in HVTN 704/HPTN 085 (NCT02716675). Receives: Other: Analytical Treatment Interruption |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 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: 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: 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: 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: 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: 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
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
Measured: 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
Measured: Measured through participant's last study visit, on average 15 months
Magnitude of HIV-specific CD4+ and CD8+ T-cells
Measured by flow cytometry
Measured: Measured through participant's last study visit, on average 15 months
Polyfunctionality of HIV-specific CD4+ and CD8+ T-cells
Measured by flow cytometry
Measured: 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
Measured: 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
Measured: 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
Measured: Measured through participant's last study visit, on average 15 months
Frequency of T- and B-cell Activation and Exhaustion Markers
Measured by flow cytometry or other cell phenotyping assays
Measured: 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.
Measured: Measured through participant's last study visit, on average 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2021
- Study start22 Aug 2022
- Primary completion22 Jul 2024
- Study completion22 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- HIV Vaccine Trials Network
- Sponsor type
- Research network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), HIV Prevention Trials Network, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Responsible party
- Sponsor
- Investigators
- Shelly Karuna, Study chair, HVTN Core, Fred HutchKatharine Bar, Study chair, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04801758
- Sponsor's protocol ID
- HVTN 804/HPTN 095
- Other IDs
- UM1AI068614
- Status last verified
- Apr 2025
- First submitted
- 1 Mar 2021
- Last updated
- 20 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antiretroviral Analytical Treatment Interruption (ATI) to Assess Immunologic and Virologic Responses in Participants Who Received VRC01 or Placebo and Became HIV-infected During HVTN 704/HPTN 085
- ClinicalTrials.gov ID
- NCT04801758
- Acronym / sponsor ID
- HVTN 804/HPTN 095
- Conditions
- HIV Infection
- Keywords
- HIV, Antibody, LTNPs, ECs, VCs, Treatment interruption
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- HIV Vaccine Trials NetworkResearch network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), HIV Prevention Trials Network, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Study start
- 22 Aug 2022 (actual)
- Primary completion
- 22 Jul 2024 (actual)
- Study completion
- 22 Jul 2024 (actual)
- First posted
- 17 Mar 2021 (actual)
- Results
- Posted 20 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Analytical Treatment Interruption | Experimental | Other: Analytical Treatment InterruptionParticipants who received VRC01 or placebo and got HIV while enrolled in HVTN 704/HPTN 085 (NCT02716675). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (32 listed)
- 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.
Key exclusion criteria (31 listed)
- Any plasma HIV-1 RNA ≥ LLOQ (LLOQ: 75, 50, 40, or 20 copies/mL) within 12 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).
- Immunosuppressive medications received within 6 months before enrollment (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatologic condition; or [4] a single course of oral/parenteral prednisone or equivalent at doses < 60 mg/day and length of therapy < 11 days with completion at least 30 days prior to enrollment).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Analytical Treatment InterruptionParticipants 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". | Other | Analytical Treatment Interruption |
Primary outcome
Time to Meeting Criteria for ART Re-initiation
Time frame: Measured through participant's last visit on Schedule 1 or 2, up to 6 months.
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
Frequency of Sustained Post-treatment HIV Control, Defined as ≥ 24 Weeks Off ART Without Meeting ART Re-initiation Criteria
Time frame: Measured at week 24 of schedule 1- monitoring ATI
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
Percentage of Participants Who Experience Adverse Events (AEs)
Time frame: Measured through participant's last study visit, up to 18 months.
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Number of Participants Reporting Serious Adverse Events (SAEs)
Time frame: Measured through participant's last study visit, up to 18 months.
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).
Number of Participants Who Discontinue ATI
Time frame: Measured through participant's last visit on Schedule 1 or 2, up to 6 months
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.
Number of Local Laboratory Values Meeting Grade 2 AE Criteria or Above
Time frame: Measured through participant's last study visit, up to 18 months
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.
9 secondary outcomes
Cumulative Incidence of Participants With First Viral Load ≥ 200 Copies/mL at Week 8, 16, and 24 of Schedule 1: Monitoring ATI
Time frame: Measured for participants undergoing ATI up at week 8, 16, and 24
Response Rate of HIV-specific CD4+ and CD8+ T-cells
Time frame: Measured through participant's last study visit, on average 15 months
Magnitude of HIV-specific CD4+ and CD8+ T-cells
Time frame: Measured through participant's last study visit, on average 15 months
Polyfunctionality of HIV-specific CD4+ and CD8+ T-cells
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
Time frame: Measured through participant's last study visit, on average 15 months
Non-neutralizing, FcγR-mediated Antibody Effector Functions
Time frame: Measured through participant's last study visit, on average 15 months
Frequency of Dendritic Cell Activation and Maturation Markers
Time frame: Measured through participant's last study visit, on average 15 months
Frequency of T- and B-cell Activation and Exhaustion Markers
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
Time frame: Measured through participant's last study visit, on average 15 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shelly Karuna study chair
HVTN Core, Fred Hutch
Katharine Bar study chair
University of Pennsylvania
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Analytical Treatment Interruption in people with HIV Infection, run by HIV Vaccine Trials Network at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Peru, Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Meeting Criteria for ART Re-initiation (time frame: Measured through participant's last visit on Schedule 1 or 2, up to 6 months.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2025.