Analytical Treatment Interruption Study of Emtricitabine/Tenofovir Alafenamide/Bictegravir in HIV-Positive Individuals with Favorable Genetic and Clinical Profiles

The primary objective is to determine the proportion of participants with a pre‑specified favorable genetic, phenotypic and clinical background who achieve viral control (HIV RNA < 50 copies/ml) during up to 24 weeks of analytical treatment interruption.

Secondary objectives include:

• Proportion of participants attaining partial viral control (<200, <400 and <1000 copies/ml) within 24 weeks of interruption.
• Time to viral rebound after treatment interruption.
• Safety monitoring during the interruption period.
• Characterization of the HIV reservoir.
• Assessment of viral inhibition relative to CD4⁺ T‑cell counts.
• Evaluation of NK and CD8⁺ cell phenotypic and functional evolution.
• Transcriptomic profiling of distinct lymphocyte subsets.
• Measurement of inflammatory, immunosenescence and immune‑activation markers.
• Determination of autologous neutralizing antibody generation.
• Development of a predictive model for post‑treatment viral control.

The trial enrolled adult individuals with HIV who were screened and pre‑selected in the exploratory study HCB/2023/0510. Eligible participants were men or women aged 18 to 65 years, generally in good health while receiving active antiretroviral treatment for at least two years and maintaining an undetectable viral load at enrollment. Inclusion required a CD4+ T‑cell count of ≥500 cells/µL at the time of analytical treatment interruption, a documented nadir CD4 count meeting disease‑stage thresholds, and a favourable genotype and NK‑cell phenotype as defined by specific HLA‑B and memory‑like NK markers. Women of child‑bearing potential needed a negative pregnancy test, and all participants had to agree to adhere to HIV preventive practices. The population was identified from the prior exploratory cohort and classified as a vulnerable patient group. The sponsor did not provide the total number of participants enrolled in the study.

The CLINIC‑CURE study is an exploratory, single‑arm pilot trial evaluating analytical treatment interruption in adults with HIV who meet predefined genetic, phenotypic and clinical criteria; participants are screened, provide written informed consent, and undergo a baseline visit confirming undetectable viral load, CD4 ≥500 cells/µL and a minimum of two years of antiretroviral therapy. After eligibility confirmation, antiretroviral therapy is discontinued (ATI) and participants attend scheduled follow‑up visits at weeks 0, 4, 12, 24, 36 and 48 for virologic, immunologic and safety assessments, with the primary endpoint measured at 24 weeks post‑ATI. The study duration for each participant spans approximately 48 weeks, concluding with an end‑of‑study visit. Early termination may occur if viral rebound (≥50 copies/mL) persists, if clinically significant symptoms or adverse events develop, or if the participant withdraws consent. The trial recruitment period is projected from September 2026 to September 2027.

The investigational product is identified as EMTRICITABINE, TENOFOVIR ALAFENAMIDE AND BICTEGRAVIR. It is supplied in the pharmaceutical form designated PHF00082MIG and is administered by the oral route. The protocol specifies a dose of 0 mg per administration; the exact dosing schedule and frequency are defined in the study’s dosing plan.

Efficacy will be evaluated primarily by determining the proportion of participants who achieve a viral load of less than 50 copies/mL at 24 weeks following analytical treatment interruption (ATI). This primary endpoint will be assessed using quantitative polymerase chain reaction (qPCR) assays performed on plasma samples collected at the week‑24 post‑ATI visit.

Secondary efficacy assessments will include:

• Proportion of participants with plasma viral loads below 200, 400, and 1,000 copies/mL at week 24 post‑ATI.
• Time to viral rebound, defined as the first occurrence of viral load ≥ 50 copies/mL, measured in weeks.
• Incidence of any clinical symptom or retroviral syndrome during the ATI period.
• Quantitative analysis of the viral reservoir using the Intact Proviral DNA Assay (IPDA) and measurement of intracellular viral RNA at weeks 0, 4, 12, 24, 36, and 48.
• In vitro viral inhibition assays (VIA) involving culture of CD4⁺ lymphocytes with CD8⁺ and/or NK cells at the same time points.
• Flow‑cytometry evaluation of lymphocyte subpopulations, including NK memory‑like cells (CD57⁺CD56⁺dim, NKG2C⁺, KIR3DL1⁺) and γδ‑CD8 subsets at weeks 0, 4, 12, 24, 36, and 48.
• Assessment of cytotoxic activity of CD4⁺, CD8⁺, and NK cells after stimulation with HIV peptides, measured at weeks 4, 12, 24, 36, and 48 and compared with baseline.
• Evaluation of NK‑cell cytotoxicity via anti‑HIV peptide responses, granzyme production, and killing assays using K562 and Raji target cells at weeks 0, 4, 12, 24, 36, and 48.
• Transcriptomic profiling of distinct lymphocyte subsets by next‑generation sequencing (NGS) at weeks 0, 4, 12, 24, 36, and 48.
• Measurement of serum markers of inflammation, immunosenescence, and immune activation at the same scheduled visits.
• Detection of autologous neutralizing antibodies at weeks 4, 8, 12, 24, 36, and 48 compared with baseline levels.
• Integration of clinical, genetic, immunologic, and virologic data to construct a predictive model of post‑treatment viral control.