Effectiveness of pegylated interferon-α combined with antiretroviral therapy on HIV reservoir clearance in acute HIV infection: study protocol for a randomised controlled trial at a tertiary infectious disease hospital in Beijing, China

Introduction HIV cure remains one of the major unsolved global health challenges. The persistence of the HIV reservoir is the key barrier to achieving viral eradication. The acute HIV infection (AHI) is crucial for reservoir establishment, making early intervention essential for long-term viral remission. Pegylated interferon-α (Peg-IFN-α) exhibits potent antiviral and immunomodulatory properties that may enhance reservoir clearance when combined with antiretroviral therapy (ART). This study aims to evaluate the efficacy and safety of Peg-IFN-α combined with ART in promoting reservoir reduction and immune reconstitution in individuals with AHI. Methods and analysis This randomised, parallel-controlled, open-label clinical trial will enrol 68 participants with confirmed AHI. Eligible participants will be randomly assigned (1:1) to receive Peg-IFN-α plus ART or ART alone. All participants will continue ART for a total of 48 weeks. The primary outcome is the percentage reduction in total HIV-1 DNA at week 48. Secondary outcomes include HIV-1 DNA reduction at week 12, CD4 + T-cell recovery, cytokine profiles and safety endpoints. Statistical analysis will be performed using the intention-to-treat principle. Recruitment commenced in April 2025 and is expected to complete by December 2027. Ethics and dissemination This study has been approved by the Ethics Committee of Beijing You’an Hospital, Capital Medical University (approval no. LL-2024-150-K). Written informed consent will be obtained from all participants before enrolment. The results will be disseminated through peer-reviewed publications, academic conferences and communications with the clinical and scientific community. De-identified datasets will be available to qualified researchers on reasonable request following publication. Trial registration number ChiCTR2500100011.