Purpose:
In resource-limited settings, antiretroviral treatment (ART) options are limited. At 1st-line ART failure, genotype drug resistance testing can identify patients with non-resistant (wild-type) virus who have failed due to poor medication adherence. These patients may safely and effectively continue 1st-line ART, avoiding premature switches to costlier 2nd-line ART.Methods: We used a state-transition, Monte Carlo simulation of HIV disease and treatment (the CEPAC-International model) to project per-person life expectancy (LE) and mean lifetime HIV care costs (2006 US$) for no genotype vs. genotype strategies at 1st-line ART failure. In the no genotype strategy, all patients switched to 2nd-line ART at diagnosis of 1st-line ART failure. In the genotype strategy, patients with wild-type virus remained on 1st-line ART with an adherence intervention, and those with resistant virus switched to 2nd-line ART. Model inputs were derived using clinical and cost data from South Africa (mean age 32.8y, mean CD4 307/µl, genotype cost $300/test, 1st-line ART $7/month, 2nd-line ART $63/month); 20% of patients had wild-type virus at 1st-line ART failure. A strategy was considered “very cost-effective” if the incremental cost-effectiveness ratio (ICER) was below the 2006 South African per capita gross domestic product ($5,400/year of life saved [YLS]). In sensitivity analyses, we examined the impact of variations in prevalence of drug resistance at 1st-line ART failure, ART efficacies, and both genotype and ART costs.
Results: At 1st-line ART failure, projected LE with no genotype was 152.4 months and increased to 155.9 months with genotype. Per-person lifetime costs were $11,690 and $11,740, respectively. Compared to no genotype, the ICER for genotype was $160/YLS. Genotype was very cost-effective under plausible variations in efficacies of 1st- and 2nd-line ART. In a 2-way sensitivity analysis, genotype was very cost-effective at the base case test cost ($300), if prevalence of wild-type virus remained >2% (Figure, circle). At the base case prevalence of wild-type virus (20%), genotype was very cost-effective at test costs <$2,600 (Figure, square); at 20% wild-type prevalence, results were not sensitive to the genotype cost since this was offset by the savings in 2nd-line ART costs.
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[Figure. Incremental cost-effectiveness ratio (ICER, 2006 USD/YLS) of genotype vs. no genotype strategy].
Conclusion: In South Africa, drug resistance testing at 1st-line ART failure increases the survival benefits of HIV treatment and is very cost-effective.
Candidate for the Lee B. Lusted Student Prize Competition