HIV-DNA and Risk of HIV-RNA Rebound After Sustained Suppression

Brief summary (registry, in English)

Brief Summary: The vast majority of people with HIV (PWH) who adhere to antiretroviral therapy achieve sustained suppression of viral replication. Despite undetectable plasma HIV RNA, HIV DNA persists in latently infected cells, and individuals may differ in their vulnerability to future treatment failure. Total and intact HIV DNA levels in virologically suppressed PWH have recently attracted interest as potential markers of HIV reservoir size and composition, which may influence the risk of viral rebound, particularly following treatment simplification to regimens with potentially lower antiviral potency. To investigate the value of HIV DNA as a marker of future treatment vulnerability, this case-control study will collect blood samples retrospectively and prospectively from PWH who experience viral rebound after at least six months of sustained virological suppression (cases) and matched PWH who remain virologically suppressed over the corresponding period (controls). Matching will be based on age, sex, and duration of virological suppression. For each participant, one peripheral blood mononuclear cell (PBMC) sample and one plasma sample will be collected within a predefined window, starting at least six months after virological suppression is achieved and ending at least three months before viral rebound in cases or the corresponding reference time in controls. PBMCs will be used to quantify total and intact HIV DNA, while plasma will be analyzed for standard soluble inflammation markers. The study aims to determine whether higher total and/or intact HIV DNA levels predict subsequent virological failure and whether these measures are associated with systemic inflammation markers. Study Title: HIV-DNA and Risk of HIV-RNA Rebound After Sustained Suppression (VIROMARKERS WP3-HIV) Background \& Rationale: Although antiretroviral therapy (ART) achieves HIV-RNA viral load suppression below 50 copies/mL in over 95% of people living with HIV (PWH), the virus persists in reservoirs and cannot be fully eradicated. Total HIV-DNA is a well-established surrogate marker of the viral reservoir; however, it often overestimates the replication-competent reservoir. The Intact Proviral DNA Assay (IPDA) allows for the specific quantification of intact proviruses capable of replication. While total HIV-DNA and intact proviral DNA show promise as candidate biomarkers to predict the risk and timing of viral rebound, their clinical utility and predictive accuracy in routine patient profiling require consolidated clinical validation. Furthermore, persistent viral expression from the reservoir may trigger chronic immune activation and systemic inflammation despite sustained plasma viral suppression. Study Objectives:To establish a standardized platform across participating research sites for quantifying total and intact HIV-DNA using stored blood, peripheral blood mononuclear cell (PBMC), or purified CD4+ T-cell samples. To evaluate the association between total/intact HIV-DNA levels and the risk of HIV-RNA viral rebound in PWH under sustained virological suppression. To assess the correlation between total/intact HIV-DNA levels and key systemic inflammatory biomarkers during suppressive ART. Study Design \& Methodology: This is an international, retrospective, and prospective observational case-control study conducted across well-characterized European cohorts of PWH. The study will analyze a minimum of 300 participants, comprising 100 "cases" who experienced virological rebound and 200 matched "controls" who maintained full virological suppression. Cases: PWH under suppressive therapy who experienced virological rebound (defined as two consecutive viral loads \>200 copies/mL or a single viral load \>1,000 copies/mL followed by an ART change). Controls: PWH matched 2:1 to cases based on age, sex, cohort, and duration of HIV-RNA suppression, who maintained HIV-RNA ≤50 copies/mL over the same follow-up timeframe. Key Eligibility Criteria. Inclusion Criteria: Adults (≥18 years) with confirmed HIV diagnosis enrolled in a cohort with regular viral load monitoring (≥2 values/year); sustained HIV-RNA ≤50 copies/mL for \>6 months under modern ART (started after 2012); availability of stored PBMC, whole blood, and plasma samples collected while suppressed; and at least 2 additional viral load measurements post-baseline. Exclusion Criteria: Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) coinfection. Study Procedures \& Biomarker Testing: Genomic Testing: stored PBMC or whole blood samples collected during viral suppression (at least 3 months prior to rebound for cases) will be analyzed central-site for total HIV-DNA and intact proviral DNA (IPDA). Proteomic Testing: plasma samples collected at matching timepoints will undergo proteomic evaluation to measure markers of inflammation/immune activation.

What you commit to

• Study type: Observational
• Planned participants: 300
• From 15 Dec 2026 to the primary completion date, Dec 2027
• No sites listed in no country
• Visits and tests: ask the trial team, the registry does not list them

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Who cannot take part

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Who the study is looking for

Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov