Rethinking HIV antibody testing in children aged 18-24 months in the OPPTIM study conducted in Johannesburg, South Africa 2018-2021.

BACKGROUND: HIV polymerase chain reaction (PCR) testing is recommended for children <18 months, and HIV antibody testing ≥18 months, limited by maternal antibody persistence. We describe seroreversion at various time points in HIV-exposed, uninfected children. METHODS: Mother-child pairs were enrolled in the "OPPTIM" study at the child's 6, 10, or 14-week clinic visit, with study visits conducted 4 July 2018 to 27 March 2021. At enrolment, 6-, 9-, 12-, 18-, 21- and 24-months, trained study staff tested children using three RDTs (DetermineTM, Uni-GoldTM and INSTI®) and a point-of-care(POC) Cepheid GeneXpert PCR test using whole blood. Abbott HIV ELISA was performed in children testing RDT non-reactive on 2 tests before 18-months, and at 18-, 21-, and 24-months. Antibody testing was performed according to the South African two-test algorithm, with RDT reactivity reported at each visit per test. Sensitivity and specificity of each test compared to HIV ELISA was assessed between 18- and 24-months. RESULTS: In the study, 403 HIV-uninfected children were enrolled; 143(35.5%), 200(49.6%) and 60(14.9%) at 6-, 10- and 14- weeks. All children tested PCR-negative at each visit timepoint. Determine RDT remained reactive in 50% of children at 12-months. In 60/245 (24.5%) children, antibody tests were reactive between 18- and 24-months. Using the South African two-test antibody algorithm, 8/245(3.3%) would have been misdiagnosed with HIV (specificity 96.7%). CONCLUSIONS: HIV antibody tests remained reactive at ≥18 months in about 25% of children. A three-test algorithm, including the use of an HIV-PCR test, will reduce misdiagnosis of HIV between 18- and 24-months.