A Mathematical Model Evaluating the Timing of Early Diagnostic Testing in HIV-Exposed Infants in South Africa

Background:Antiretroviral therapy is often initiated too late to impact early HIV-related infant mortality. Earlier treatment requires an earlier diagnosis, and the currently recommended 6-week HIV polymerase chain reaction (PCR) test needs reconsideration. This study aims to identify (1) optimal testing intervals to maximize the number of perinatal HIV infections diagnosed and (2) programmatic issues that impact diagnosis.Methods:A mathematical model was developed to simulate antiretroviral prophylaxis uptake and health outcomes in 240,000 HIV-exposed South African infants. The model considered routine early testing with 1 PCR (at birth, 6, 10, or 14 weeks of age) and with 2 PCR tests (at birth and at 6, 10, or 14 weeks of age).Results:A single 6-week test would diagnose the same number of perinatal HIV infections as birth testing (P = 0.92) but fewer infections than a 10-week test (P < 0.01). Ten-week testing identifies the highest number of perinatally infected infants (P < 0.01 compared with a single test at all other ages) but does not save additional life years compared with birth testing (P = 0.27). Performing 2 PCR tests (at birth and 10 weeks) would identify the highest number of perinatal infections (P < 0.01 versus a second 6- or 14-week test). However, 25% of perinatal HIV infections would remain undiagnosed, largely because of failure to return PCR test results to caregivers.Conclusions:Six weeks may no longer be the optimal age to diagnose perinatal HIV infections. Two early PCR tests (at birth and 10 weeks) would likely be the ideal diagnostic algorithm, but must be coupled with improved program coverage.