Observational PIC Destination Cohort

Official title

An Observational Post-Intervention Control Destination Cohort

Overview

This study is being done to see if people who control HIV without antiretroviral therapy (ART) after receiving an intervention can remain off ART safely. The information collected in this study is also being used to try to understand how people control HIV without ART after receiving an intervention.

Detailed description

This study is a two-step non-interventional study for participants who achieved prolonged viral control off ART, post-intervention (post-intervention control \[PIC\]) in qualifying AIDS Clinical Trials Group (ACTG) and non-ACTG interventional cure trials (parent studies).

Primary outcome measures

• Occurrence of an SAE or Grade ≥3 AE that is related to ATI [Time frame: From study entry to 96 weeks]
• Change in CD4 percentage from parent study (pre-ATI) to Step 1 timepoints [Time frame: From study entry to 96 weeks]
• Occurrence of new diagnoses of interest [Time frame: From study entry through 144 weeks]
• Time from ATI to sustained HIV-1 RNA ≥1000 copies/mL [Time frame: From study entry to 96 weeks]
• HIV RNA below 200 copies/mL [Time frame: 24 weeks after re-starting ART]
• Change in CD4% from pre-ATI to Step 2 [Time frame: From study entry to Step 2 week 24]
• Measurements of reservoir [Time frame: From 24 weeks to 48 weeks after ART restart]

Secondary outcome measures (5)

• Time from ATI to ART restart due to a viral, immune, or clinical reason [Time frame: From study entry to 96 weeks]
• Time from ATI to ART restart [Time frame: From study entry to 96 weeks]
• Measurement of circulating reservoir [Time frame: Every 24 weeks in Step 1 (up to 96 weeks) and Step 2 Week 24 and 48]
• Plasma HIV-1 RNA at each study visit [Time frame: From study entry to 144 weeks]
• Measurement of replication-competent virus [Time frame: Every 24 weeks in Step 1 (up to 96 weeks) and Step 2 Week 24 and 48]

Eligibility criteria

Step 1 Inclusion Criteria:

• Currently or previously enrolled in a qualifying ACTG or non- ACTG parent study of curative or suppressive HIV therapy that included an ATI.
• If feasible, participants should not remain co-enrolled in their respective parent study after entering A5385.
• Achieved at least 24 weeks of HIV virus suppression (as defined by the parent study) following ATI initiation, remains off ART with <4 consecutive weeks of HIV-1 RNA >1000 copies/mL, CD4+ T-cell count > 350 cells/mm3 and not experiencing symptoms of acute retroviral syndrome.

NOTE: Participants whose participation has ended on the parent study may still qualify if they have not resumed ART, meet A5385's eligibility criteria, and have not met A5385 ART restart criteria.

• CD4+ T cell count >350 cells/mm3 obtained within 28 days prior to study entry at any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any network-approved non-US laboratory that is IQA certified.
• Willingness to continue ATI for up to 96 weeks or until ART restart criteria are met, and to remain in follow up for 48 weeks after ART restart.
• For participants who are able to become pregnant, negative serum or urine pregnancy test within 24 hours prior to study entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs.

NOTE A: Participants who are able to become pregnant are individuals who have not been post-menopausal for at least 24 consecutive months, who have had menses within the preceding 24 months, and who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy, tubal ligation, or bilateral salpingectomy.

NOTE B: Acceptable documentation of hysterectomy and bilateral oophorectomy, tubal ligation, and tubal micro-inserts: written documentation or oral communication from a clinician or clinician's staff documented in source documents (physician report/letter, operative report or other source documentation in the patient record, discharge summary, laboratory report, etc.). Participant-reported history is acceptable for documentation of menopause.

• Participants who are able to become pregnant and are engaging in sexual activity that could lead to pregnancy must agree to use one highly effective method of contraception throughout the course of the study from the list below.

Acceptable methods of contraception include:

• Barrier method
• Contraceptive subdermal implant
• Intrauterine device or intrauterine system
• Combined estrogen and progestogen oral contraceptive
• Injectable progestogen
• Contraceptive vaginal ring
• Percutaneous contraceptive patches
• Male partner sterilization with documentation of azoospermia prior to the female participant's entry into the study, and this male is the sole partner for that participant.

• Willingness to use barrier protection (male or female) during sexual activity with all partners not on effective pre-exposure prophylaxis (PrEP) throughout Step 1 ATI and until viral re-suppression in Step 2.

NOTE: Effective PrEP includes ART treatment for partners living with HIV infection.

• Ability and willingness of participant to provide informed consent.

Step 2 Inclusion Criteria:

• Met A5385 ART restart criteria in Step 1.
• Willingness to use barrier protection (male or female) during sexual activity with all partners not on effective PrEP until viral re-suppression.

NOTE: Effective PrEP includes ART treatment for partners living with HIV infection.

Step 1 Exclusion Criteria:

• Intercurrent illness, new medical diagnosis, laboratory abnormality, sign, or symptom that, in the opinion of the site investigator, would place participant at higher risk of morbidity during continued ATI.
• Medical or psychiatric condition (including pregnancy or breastfeeding) that, in the opinion of the site investigator, would place the participant at higher risk of morbidity or would interfere with adherence to study requirements.

NOTE: Site investigators should exercise caution in invoking these criteria and instead aim to support potential participants who are interested and otherwise eligible to participate in the study.

Step 2 Exclusion Criteria:

• Medical or psychiatric condition that, in the opinion of the site investigator, would place the participant at higher risk of morbidity or would interfere with adherence to study requirements.

NOTE: Site investigators should exercise caution in invoking these criteria and instead aim to support potential participants who are interested and otherwise eligible to participate in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 4 centers

• University of California, San Francisco HIV/AIDS CRS (801) — San Francisco
• Washington University Therapeutics (WT) CRS (2101) — St Louis
• Weill Cornell Upton CRS (7803) — New York
• Case CRS (2501) — Cleveland

Identifiers

NCT: NCT05985642 · ACTG A5385 · UM1AI068636

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗