Antiretroviral therapy (ART) decreases morbidity and mortality in patients with HIV/AIDS, both in industrialized and less developed settings. Important questions about the use of ART remain: key among them is the optimal time to initiate ART in resource-poor settings. Current World Health Organization (WHO) guidelines recommend treatment initiation later in the course of the disease than the US Department of Health and Human Services and the International AIDS Society guidelines. There is currently no consensus on the issue. Policy decisions regarding the timing of ART initiation must incorporate complex trade-offs among clinical benefits, risks of medication-related toxicity, human resource requirements, financial cost, treatment efficacy, adherence, and drug resistance. The candidate proposes to address this issue by conducting a cost-effectiveness analysis of early versus delayed ART in a study that is separate but complementary to the CIPRA HT 001 randomized clinical trial that is underway at the GHESKIO Center (Haitian Study Group on Kaposi's Sarcoma and Opportunistic Infections) in Haiti. The ongoing clinical trial randomizes patients with pre-AIDS disease (WHO stage I, II, or III) and CD4 cells counts between 200 and 350 to early (within 2 weeks) versus delayed (CD4 <200 or clinical AIDS) ART. The primary outcome for the CIPRA trial is survival. The candidate's proposed research will add critical information regarding the impact of adherence and the cost-effectiveness of early versus delayed ART. The research plan of the proposed decision model is composed of two specific aims: 1. To compare adherence to ART and adherence barriers between patients in the early and delayed treatment groups in the CIPRA trial. Adherence will be measured by pharmacy pill counts and by patient self-report. 2. To conduct a cost-effectiveness analysis comparing early versus delayed ART in Haiti in the presence or absence of tuberculosis from a societal perspective. Outcome measures will include life expectancy, lifetime total direct medical costs, and cost-effectiveness in dollars per life-year gained. Sensitivity analyses will examine the impact of adherence rates, hospitalization rates, and cost of ART. This research is relevant to public health, as this will be the first cost-effectiveness analysis of the timing of ART initiation that is based on randomized clinical trial data, and will impact the treatment of HIV globally.
