Accuracy and performance of the WHO 2015 and WHO 2019 HIV testing strategies across epidemic settings

TLDR: As positivity among persons testing for HIV reduces below 5% in nearly all settings, implementation of the WHO 2019 testing strategy will ensure that positive predictive value remains above the 99% target threshold, averting misdiagnoses and ART initiations among HIV unin infected people.

Abstract: Background WHO 2019 HIV testing guidelines recommended a standard HIV testing strategy consisting of three consecutively HIV-reactive test results on serology assays to diagnose HIV infection. National HIV programmes in high prevalence settings currently using the strategy consisting of only two consecutive HIV-reactive tests should consider when to implement the new guideline recommendations. Methods and Findings We implemented a probability model to simulate outcomes of WHO 2019 and the two strategies recommended by WHO 2015 guidelines on HIV testing services. Each assay in the strategy was assumed independently 99% sensitivity and 98% specificity, the minimal thresholds required for WHO prequalification. For each strategy and positivity ranging 20% to 0.2%, we calculated the number of false-negative, false-positive, and inconclusive results; positive and negative predictive value (PPV, NPV); number of each assay used, and testing programme costs. We found that the NPV was above 99.9% for all scenarios modelled. Under the WHO 2015 two-test strategy, the PPV was below the 99% target threshold when positivity fell below 5%. For the WHO 2019 strategy, the PPV was above 99% for all positivity levels. The number reported ‘inconclusive’ was higher under the WHO 2019 strategy. Implementing the WHO 2019 testing strategy in Malawi, would require around 89,000 A3 tests in 2021, compared to 175,000 A2 tests and over 4.5 million A1 tests per year. The incremental cost of the WHO 2019 strategy was less than 2% in 2021 and declined to 0.9% in 2025. Conclusions As positivity among persons testing for HIV reduces below 5% in nearly all settings, implementation of the WHO 2019 testing strategy will ensure that positive predictive value remains above the 99% target threshold, averting misdiagnoses and ART initiations among HIV uninfected people. The incremental cost of implementing the WHO 2019 HIV testing strategy compared to the two-test strategy is negligible because the third assay accounts for a small and diminishing share of total HIV tests.