Association between different levels of suppressed viral load and the risk of sexual transmission of HIV among serodiscordant couples on antiretroviral therapy: a protocol for a two-step systematic review and individual participant data meta-analysis.

Introduction: HIV is a major global public health issue. The risk of sexual transmission of HIV in serodiscordant couples when the partner living with HIV maintains a suppressed viral load of <200 copies of HIV copies/mL has been found in systematic reviews to be negligible. A recent systematic review reported a similar risk of transmission for viral load<1000 copies/mL, but quantitative transmission risk estimates were not provided. Precise estimates of the risk of sexual transmission at sustained viral load levels between 200 copies/mL and 1000 copies/mL remain a significant gap in the literature.

Methods And Analysis: A systematic search of various electronic databases for the articles written in English or French will be conducted from January 2000 to October 2023, including MEDLINE, Embase, the Cochrane Central Register of Controlled Trials via Ovid and Scopus. The first step of a two-step meta-analysis will consist of a systematic review along with a meta-analysis, and the second step will use individual participant data for meta-analysis. Our primary outcome is the risk of sexual HIV transmission in serodiscordant couples where the partner living with HIV is on antiretroviral therapy. Our secondary outcome is the dose-response association between different levels of viral load and the risk of sexual HIV transmission. We will ascertain the risk of bias using the Risk Of Bias in Non-randomised Studies of Interventions (ROBINS-I) and Quality in Prognostic Studies (QUIPS), the risk of publication bias using forest plots and Egger's test and heterogeneity using I. A random effects model will estimate the pooled incidence of sexual HIV transmission, and multivariate logistic regression will be used to assess the viral load dose-response relationships. The Grading of Recommendations, Assessment, Development and Evaluation system will determine the certainty of evidence.

Ethics And Dissemination: The meta-analysis will be conducted using deidentified data. No human subjects will be involved in the research. Findings will be disseminated through peer-reviewed publications, presentations and conferences.

Prospero Registration Number: CRD42023476946.