To ensure >99% positive predictive value (PPV) for HIV testing strategies (HTS) in all settings, WHO 2015 Guidelines recommended two consecutive reactive HIV tests to diagnose HIV infection in high-prevalence (>5%) and three consecutive reactive tests in low-prevalence (≤5%) settings. As awareness of HIV status and treatment coverage reaches high levels, positivity among HTS clients is now below 5% even in high HIV prevalence settings. Consequently, countries employing the ‘high-prevalence’ strategy should consider if, when, and how to transition to a strategy with three-assays for HIV diagnosis. We estimated the HIV testing outcomes, commodities required, and incremental cost for the 3-test versus 2-test strategy.
We created a probability model to simulate HIV testing outcomes of the high- and low-prevalence strategies recommended in WHO 2015 HTS Guidelines, including recommended repetition of discrepant assays. We assumed each assay in the algorithm had 99% sensitivity and 98% specificity, minimum thresholds required to obtain WHO prequalification. Fully loaded costs indicative of a low/middle-income setting were US$2 per client plus commodity costs of $1.30, $2.30, and $2.50 per A1, A2, and A3 assay used, respectively. We calculated expected HIV testing outcomes per 100,000 persons tested with positivity ranging from 0.1% to 20%: expected number of false-positive and false-negative misclassifications, positive and negative predictive value, number of each assay used, and total cost.
The expected number of false-positive misclassifications reduced from around 45 to fewer than 1 per 100,000 tested for the 3-test strategy at all positivity levels (Table 1). The PPV of the testing strategy was well above the 99% target at all positivity levels for the 3-test strategy. The number of A1 and A2 assays utilized did not change; the number of A3 assays required was expectedly greater with the 3-test strategy but still much lower than the number of A2 required. The total cost of the 3-test strategy was only 2.5% greater than the 2-test strategy at 5% positivity, reflecting that HTS cost programme cost is primarily determined by the number of A1 conducted.
The 3-test strategy ensured high PPV at all HIV positivity levels for a modest incremental cost relative to the 2-test strategy. In light of low positivity, we suggest all countries transition to a unified strategy with three reactive tests for HIV diagnosis in accordance with latest WHO guidance released in 2019.