Observational PIC Destination Cohort

ConditionHIV-1-infection

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18+

SponsorAdvancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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.

Disqualifiers

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.

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.

Trial population

Participants who achieved prolonged viral control off ART post-intervention (post-intervention control \[PIC\]) in qualifying ACTG and non-ACTG interventional cure trials (parent studies).

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Not listed

Trial groups

30 Participants

are grouped into 1 trial group

Group A: Observational PIC Destination Cohort

Trial outcomes

Primary outcomes

Occurrence of an SAE or Grade ≥3 AE that is related to ATI

The proportion of participants reporting a serious adverse event (SAE) or a grade ≥ 3 adverse event (AE) that was judged by the A5385 clinical management committee to be at least possibly related to ATI during Step 1. An AE is any unfavorable and unintended sign, symptom, or diagnosis occurring in a study participant during the conduct of the study regardless of the attribution. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation or existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient or require intervention to prevent one of the outcomes listed above. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death.

Time frame

From study entry to 96 weeks

Change in CD4 percentage from parent study (pre-ATI) to Step 1 timepoints

Changes in CD4 percentage (CD4%) are calculated as the CD4% at the specified Step 1 timepoint minus the CD4% measured at the pre-ATI timepoint in the qualifying parent study.

Time frame

From study entry to 96 weeks

Occurrence of new diagnoses of interest

Occurrence of new diagnoses of interest during Step 1 and Step 2.

Time frame

From study entry through 144 weeks

Time from ATI to sustained HIV-1 RNA ≥1000 copies/mL

Time from ATI to sustained HIV-1 RNA ≥1000 copies/mL over a 4-week period during Step 1.

Time frame

From study entry to 96 weeks

Secondary outcomes

Time from ATI to ART restart due to a viral, immune, or clinical reason

Time from ATI to ART restart due to a viral reason (plasma HIV-1 RNA ≥1000 copies/mL for ≥4 consecutive weeks without at least a 0.2 log10 decline from the previous week), and immune reason (confirmed CD4+ T cell count \<350), or a clinical reason (e.g., acute retroviral syndrome).

Time frame

From study entry to 96 weeks

Time from ATI to ART restart

Time from ATI to ART restart, for any reason.

Time frame

From study entry to 96 weeks

Measurement of circulating reservoir

Cell-associated HIV-1 DNA and HIV-1 RNA measured in CD4+ T cells.

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

Plasma HIV-1 RNA (copies/mL) at each study visit measured by clinical assay, or if unquantifiable by standard clinical assay (e.g., below the limit of quantification), single copy assay.

Time frame

From study entry to 144 weeks

Other outcomes

Biomarkers of systemic inflammation and immune activation

Measurements of plasma soluble biomarkers of systemic inflammation and immune activation every 24 weeks during ATI and at 24 and 48 weeks after ART restart.

Time frame

From 24 weeks to 48 weeks after ART restart

Anti-HIV cellular humoral and innate responses

Anti-HIV cellular humoral and innate responses every 24 weeks during ATI and at 24 and 48 weeks after ART restart.

Time frame

From 24 weeks to 48 weeks after ART restart

Association of viral or host characteristics with time to ART restart

Viral or host characteristics, including, but not limited to, laboratory measures (e.g., viral, inflammatory, reservoir, immune measures), host genetics (e.g., CCR5 heterogeneity, HLA type), or host demographics (e.g., gender, biologic sex, age) for association with time to meeting HIV-1 related, or any, ART restart criteria.

Time frame

From study entry to 96 weeks

Virus properties and immune responses surrounding time of viral rebound

Properties of rebound virus, including genotype and phenotype by relevant assays, and immune response surrounding time of viral rebound.

Time frame

From study entry to 96 weeks