Purpose: In resource-limited settings, increasing numbers of HIV-infected individuals are initiating ART and remaining in care longer. Many HIV budgets, however, are flattening or decreasing. By modeling a policy of discontinuing ART after treatment failure, we aimed to highlight trade-offs among competing policy goals of optimizing individual health outcomes, population health outcomes, and the number receiving treatment.
Method: We assessed three HIV treatment strategies: (1) no ART; (2) never discontinue ART (Status Quo); and (3) discontinue ART after failure (Alternative). We used a state-transition model (CEPAC-International) to simulate annual probabilities of survival and receiving ART for treatment-eligible, HIV-infected individuals in the absence of treatment constraints. These estimates were then fed into a population-level linear programming model that included constraints on treatment capacity. For simplicity, we assumed that incidence of new patients and treatment capacity were constant over time. Data were derived from clinical trials and cohort studies conducted in Côte d’Ivoire, West Africa. Treated individuals received two sequential ART regimens; switching to 2nd-line ART and discontinuation of 2nd-line ART (Alternative strategy only) occurred upon detection of antiretroviral failure, defined as a 50% decrease in peak CD4 count. Individuals receiving a failed ART regimen continued to experience some treatment benefit, including decreased risk of AIDS-related mortality. At the population level, we assumed an analytic time horizon of 5 years and the number of treatment-eligible cases (100,000/year) exceeded treatment capacity (25,000/year).
Result: At the population level, including treated and untreated individuals, the Alternative strategy increased total life-years by 10,000 (+0.8%) to 1.23 million compared to the Status Quo strategy. The Alternative strategy increased the average number initiating ART annually by 180 individuals (+13.3%) to 1,530 compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for treated individuals decreased by 0.8 years (-4.6%) to 16.4 years compared to the Status Quo. Among patients receiving ART over the 5-year period, 20.7% died under the Alternative strategy compared to 18.7% under the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and level of treatment capacity.
Conclusion: With limited HIV treatment resources, trade-offs emerge between maximizing health outcomes for individual patients receiving treatment and maximizing health outcomes and access to treatment at the population level.
Candidate for the Lee B. Lusted Student Prize Competition