BACKGROUND

Persistent virological non-suppression among people with HIV receiving tenofovir-lamivudine-dolutegravir (TLD) can result from poor adherence with or without resistance; however, genotypic resistance testing (GRT) is not recommended routinely in South Africa. We examined the clinical and economic effect of GRT for all South African adults diagnosed with persistent virological non-suppression on TLD.

METHODS

In this modelling study, we used the previously validated Cost-Effectiveness of Preventing AIDS Complications-International microsimulation model to compare three strategies: (1) continued TLD (baseline); (2) immediate switch to tenofovir-lamivudine plus ritonavir-boosted darunavir; and (3) GRT prompting switch to tenofovir-lamivudine plus ritonavir-boosted darunavir for people with dolutegravir resistance or TLD continuation for people without dolutegravir resistance. We estimated that 2·3% and 28·5% of the baseline population have dolutegravir resistance and nucleoside reverse transcriptase inhibitor (NRTI) resistance, respectively. We also examined the effect of a low-cost, point-of-care urine tenofovir test in development to detect recent antiretroviral therapy use (84% sensitivity and 50% specificity), with GRT only when positive. Costs included GRT (US$157 per test), TLD ($45 per year), tenofovir-lamivudine plus ritonavir-boosted darunavir ($247 per year), and urine tenofovir testing ($2 per test). Outcomes included life-years, costs (provider perspective), and incremental cost-effectiveness ratios (ICERs; $ per disability-adjusted life-year [DALY]). We considered cost-effectiveness thresholds of less than $3310 per DALY (base case) and less than $1100 to $4250 per DALY.

FINDINGS

Based on our model, we estimated that continued TLD results in 14·11 undiscounted life-years and costs $5380 discounted at 3%; GRT results in 14·36 life-years and costs $5860 (0·14 discounted DALYs averted; ICER $3500 per DALY). Immediate switch results in fewer DALYs averted and higher costs. GRT has an ICER of $3310 per DALY or less when baseline dolutegravir resistance prevalence is ≥2·5% or genotypic resistance test costs ≤$147 per test. Urine tenofovir testing to identify GRT eligibility results in an ICER of $2300 per DALY; the ICER would be less than $1100 per DALY if urine test specificity is 0·87 or greater and costs $2 per test or test specificity is higher than 0·98 and costs $10 per test or less.

INTERPRETATION

GRT could increase life expectancy for people with HIV and persistent virological non-suppression on TLD in South Africa and could be cost-effective, especially at lower test costs. At current effectiveness and costs of tenofovir-lamivudine plus ritonavir-boosted darunavir, an immediate switch would not be preferred.

FUNDING

National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the MGH Jerome and Celia Reich Endowed Scholar in HIV/AIDS Research Award.