An Observational Study of Long-term Outcomes of HIV-1 Infection in Persons Who Become HIV-1 Infected After Enrollment in HIV-1 Vaccine Trials

Completed

• Conditions: HIV Infections
• Interventions: Other: Observation

• Registration Number: NCT03337906
• Lead Sponsor: HIV Vaccine Trials Network

Brief Summary

An observational study of long-term outcomes of HIV-1 infection in persons who become infected after enrollment in HIV-1 vaccine trials

Detailed Description

A descriptive and observational study of long-term outcomes of HIV-1 infection in persons who become HIV-1 infected after enrollment in HIV-1 vaccine trials

Study Timeline

• Study Start: 2008-07-11
• Primary Completion: 2015-07-11
• Study Completion: 2016-07-01
• Study First Submitted: 2017-11-07
• Study First Submitted QC: 2017-11-07
• Study First Posted: 2017-11-09
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-11
• Last Update Posted: 2022-04-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 209

Inclusion Criteria

• Participants must meet the following criteria in order to be eligible for inclusion in the study:

  1. Confirmation of HIV-1 infection after enrollment in an HVTN vaccine trial in which HIV-1 infection constituted an endpoint, according to the diagnostic algorithm specified in the parent protocol.
  2. Ability and willingness to provide written informed consent to participate in the study.
  3. Ability and willingness to adhere to the on-study follow-up schedule.
  4. Ability and willingness to provide adequate information for locator purposes.
  5. Participants who are currently on ART or who previously received antiretrovirals as part of post-exposure prophylaxis, pre-exposure prophylaxis, or previous treatment regimen will be eligible for inclusion in this protocol. Their previous treatment history will be collected. If a participant has been on ART for more than 2 years, please consult with the protocol team leadership prior to enrollment.
  6. For participants initiating ART, agreement of participant and PHCP to initiate potent and durable ART regimens in accordance with local and international guidelines. Examples of potent and durable regimens are provided in Appendix H. Participants who initiate ART not consistent with regimens outlined in Appendix H may enroll with permission of the protocol chair or designee(s).

Exclusion Criteria

• Persons who meet the following criteria will be excluded from the study:

  1. Any medical, psychiatric, alcohol/drug dependency or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence or a participant's ability to give informed consent.
  2. Participants who meet these additional criteria will be excluded from the study:

• Participants undergoing acute therapy for serious medical illnesses (in the opinion of the site investigator) within 14 days prior to initiation of ART.

• Participants with chronic, acute, or recurrent infections that are serious (in the opinion of the site investigator).

• Participants who must continue with chronic (maintenance) therapy (e.g., tuberculosis [TB], pneumocystis pneumonia [PCP]), must have completed at least 14 days of therapy and be clinically stable prior to initiation of ART.

• Oral and vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses, as defined by the site investigator, present no restriction to eligibility.

• Participants undergoing radiation therapy, systemic chemotherapy, or receiving an immunomodulator within 45 days prior to initiation of ART. (A tapering course of corticosteroids as acute therapy for PCP or other conditions is an exception.)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Participants infected with HIV-1	Observation	Persons who become HIV-1 infected after enrollment in HIV-1 vaccine trials

Primary Outcome Measures

Name	Time	Method
Measure plasma HIV-1 RNA levels and CD4+ T cell counts longitudinally	8 years	Blood samples will be processed for PBMCs and then cryopreserved. These specimens will be stimulated with synthetic HIV-1 peptide pools. This process will allow ex vivo HIV-specific T-cell responses to be assessed by IFN-γ ELISpot and/or flow cytometry.
Measure time to initiation of ART	8 years	Blood samples will be processed for PBMCs and then cryopreserved. These specimens will be stimulated with synthetic HIV-1 peptide pools. This process will allow ex vivo HIV-specific T-cell responses to be assessed by IFN-γ ELISpot and/or flow cytometry.
Measure time to HIV-1 related clinical events	8 years	Blood samples will be processed for PBMCs and then cryopreserved. These specimens will be stimulated with synthetic HIV-1 peptide pools. This process will allow ex vivo HIV-specific T-cell responses to be assessed by IFN-γ ELISpot and/or flow cytometry.; Responses from ELISpot assays will be reported as the number of spot-forming cells Blood samples will be processed for PBMCs and then cryopreserved. These specimens will be stimulated with synthetic HIV-1 peptide pools. This process will allow ex vivo HIV-specific T-cell responses to be assessed by IFN-γ ELISpot and/or flow cytometry.
Proportion of individuals with plasma HIV-1 RNA level <50 copies/mL at 24 weeks after initiation of ART	8 years	Blood samples will be processed for PBMCs and then cryopreserved. These specimens will be stimulated with synthetic HIV-1 peptide pools. This process will allow ex vivo HIV-specific T-cell responses to be assessed by IFN-γ ELISpot and/or flow cytometry.; Responses from ELISpot assays will be reported as the number of spot-forming cells Blood samples will be processed for PBMCs and then cryopreserved. These specimens will be stimulated with synthetic HIV-1 peptide pools. This process will allow ex vivo HIV-specific T-cell responses to be assessed by IFN-γ ELISpot and/or flow cytometry.

Secondary Outcome Measures

Name	Time	Method
Time from initiation of ART to treatment failure due to virologic, immunologic, and clinical reasons	8 years	Blood samples will be processed for PBMCs and then cryopreserved. These specimens will be stimulated with synthetic HIV-1 peptide pools. This process will allow ex vivo HIV-specific T-cell responses to be assessed by IFN-γ ELISpot and/or flow cytometry.
Occurrence of HIV/AIDS associated events, including death	8 years	Blood samples will be processed for PBMCs and then cryopreserved. These specimens will be stimulated with synthetic HIV-1 peptide pools. This process will allow ex vivo HIV-specific T-cell responses to be assessed by IFN-γ ELISpot and/or flow cytometry.
Adherence information collected at 24, 48, 96, and 144 weeks following initiation of ART	24, 48, 96, and 144 weeks	Blood samples will be processed for PBMCs and then cryopreserved. These specimens will be stimulated with synthetic HIV-1 peptide pools. This process will allow ex vivo HIV-specific T-cell responses to be assessed by IFN-γ ELISpot and/or flow cytometry.
Side effects collected at 24, 48, 96, and 144 weeks following initiation of ART	24, 48, 96, and 144 weeks	Blood samples will be processed for PBMCs and then cryopreserved. These specimens will be stimulated with synthetic HIV-1 peptide pools. This process will allow ex vivo HIV-specific T-cell responses to be assessed by IFN-γ ELISpot and/or flow cytometry.
Proportion of subjects with HIV-1 RNA level <50 copies/mL post-initiation of ART; log change in plasma HIV-1 RNA levels and change in CD4+ T cell levels between baseline (at initiation of ART) and post-initiation of ART	24, 48, 96, and 144 weeks	Blood samples will be processed for PBMCs and then cryopreserved. These specimens will be stimulated with synthetic HIV-1 peptide pools. This process will allow ex vivo HIV-specific T-cell responses to be assessed by IFN-γ ELISpot and/or flow cytometry.

Trial Locations

Locations (21)

UIC Project WISH CRS; 🇺🇸 Chicago, Illinois, United States

The Hope Clinic of the Emory Vaccine Center CRS; 🇺🇸 Decatur, Georgia, United States

Brigham and Women's Hospital Vaccine CRS (BWH VCRS); 🇺🇸 Boston, Massachusetts, United States

NY Blood Ctr./Union Square CRS; 🇺🇸 New York, New York, United States

Fenway Health Clinical Research Site CRS; 🇺🇸 Boston, Massachusetts, United States

Columbia P&S CRS; 🇺🇸 New York, New York, United States

NY Blood Ctr./Bronx CRS; 🇺🇸 New York, New York, United States

University of Rochester Vaccines to Prevent HIV Infection CRS; 🇺🇸 New York, New York, United States

Penn Prevention CRS; 🇺🇸 Philadelphia, Pennsylvania, United States

Seattle Vaccine and Prevention CRS; 🇺🇸 Seattle, Washington, United States

Soweto HVTN CRS; 🇿🇦 Johannesburg, Gauteng, South Africa

eThekwini CRS; 🇿🇦 Durban, Kwa Zulu Natal, South Africa

Aurum Institute Klerksdorp CRS; 🇿🇦 Klerksdorp, North West Province, South Africa

Bridge HIV CRS; 🇺🇸 San Francisco, California, United States

ACSA CRS; 🇵🇪 Iquitos, Maynas, Peru

Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS; 🇭🇹 Port-au-Prince, Haiti

Unidad de Vacunas IDCP-COIN-DIGECITSS CRS; 🇩🇴 Santo Domingo, Dominican Republic

Emavundleni CRS; 🇿🇦 Cape Town, Western Cape, South Africa

Vanderbilt Vaccine (VV) CRS; 🇺🇸 Nashville, Tennessee, United States

Maternal-Infant Studies Center (CEMI) CRS; 🇵🇷 San Juan, Puerto Rico

Alabama Vaccine CRS; 🇺🇸 Birmingham, Alabama, United States