Development and validation of systems for rational use of viral load testing in adults receiving first-line ART in sub-Saharan Africa

Background: World Health Organization (WHO) immunological and clinical criteria for monitoring first-line antiretroviral treatment (ART) offer low accuracy for predicting viral failure. Targeting viral load assays to those at high risk has been recommended and a system to do this has been developed in Cambodia. Systems for use in sub-Saharan African populations were evaluated. Methods: A new Ugandan-based scoring system for targeting viral load assays was developed from data from the first 4 years of a Ugandan cohort (N = 559) receiving first-line ART. The accuracy of this, the Cambodian system and the WHO criteria to predict viral failure, through targeting viral load assays, were compared in a separate population of 496 Ugandans. Results: The new Ugandan scoring system included CD4 cell count, mean cell volume, adherence, and HIV-associated clinical events as predictors of viral failure. In the validation population, the Ugandan system undertook viral load assays in 61 (12.3%) cases offering 20.5% sensitivity and 100% positive predictive value (PPV) to predict viral failure. The Cambodian system undertook viral load assays in 33 (6.7%) cases producing 23.1% sensitivity and 90.0% PPV. WHO criteria recommended viral load assays in 72 (14.5%) cases offering 30.8% sensitivity and 100% PPV. Conclusion: Locally developed algorithms based on clinical and immunological criteria may offer little additional accuracy over WHO criteria for targeting viral load assays. When possible, confirming viral load before switching therapy is recommended. Scoring systems are more flexible than WHO criteria in allowing ART providers to choose the proportion of the population that undergo targeted viral load testing.