Optimizing HIV Care in Less Developed Countries

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Project Summary/Abstract Despite improved access to HIV testing and antiretroviral therapy over the past decade, people with HIV globally continue to experience high mortality from HIV-associated infections such as cryptococcal meningitis. Cryptococcal meningitis causes more than 90,000 deaths annually, 75% of which occur in sub- Saharan Africa. Most of these deaths would be preventable with improved access to high-quality diagnostics and safe, effective treatment regimens. However, mortality from cryptococcal meningitis remains unacceptably high (70%-80%) due to challenges including unreliable supply of diagnostic tests, low testing rates among at-risk individuals, lack of equipment and trained staff to perform diagnostic tests, limited access to more effective treatments, and high drug and hospitalization costs for people with cryptococcal meningitis. It is critically important to determine which specific interventions would be most effective to improve access to cryptococcal meningitis testing and treatment and reduce cryptococcal meningitis-related mortality, given budget constraints in resource-limited settings. In the parent R37 (R37AI058736), the PI (Dr. Kenneth Freedberg) and research team have developed and utilized the Cost-Effectiveness of Preventing AIDS Complications International (CEPAC-I) model, a computer microsimulation of the natural history, clinical management, outcomes, costs, and cost- effectiveness of HIV treatment. Past and ongoing analyses have included a focus on HIV testing, treatment, and prevention strategies in multiple international settings. This administrative supplement proposes to: 1) expand the CEPAC-I model to include the clinical outcomes and costs of cryptococcal meningitis testing and treatment, and 2) to assess the clinical implications and cost effectiveness of testing and treatment strategies to improve outcomes from cryptococcal meningitis in South Africa. The research team will populate the novel model structure using data from published literature supplemented by estimates from in- country collaborators. Intervention strategies will span the cryptococcal meningitis care continuum and will include improving access to and uptake of lumbar puncture and cryptococcal antigen lateral flow assay testing, investing in linkage-focused interventions, and expanding access to key treatment drugs (i.e., flucytosine and amphotericin B). This proposed analysis will examine the survival benefit and costs associated with scaling up capacity and distribution for each of these interventions individually and in combination; results will inform clinicians and policymakers in South Africa and similar settings. Further, the novel model expansion will provide a platform for investigating additional important clinical and policy questions related to cryptococcal meningitis and other chronic HIV-associated infections.