Could early antiretroviral therapy entail more risks than benefits in sub-Saharan African HIV-infected adults? A model-based analysis

Background: Initiation of antiretroviral therapy (ART) in all HIV-infected adults, regardless of CD4(+) T-cell count, is a proposed strategy for reducing HIV transmission. We investigated the conditions under which starting ART early could entail more risks than benefits for patients with high CD4(+) T-cell counts. Methods: We used a simulation model to compare ART initiation upon entry to care (`immediate ART') to initiation at CD4(+) T-cell count = 350 cells/mu l (`WHO 2010 ART') in African adults with CD4(+) T-cell counts > 500 cells/mu l. We varied inputs to determine the combination of parameters (population characteristics, conditions of care, treatment outcomes) that would result in higher 15-year mortality with immediate ART. Results: The 15-year mortality was 56.7% for WHO 2010 ART and 51.8% for immediate ART. In one-way sensitivity analysis, lower 15-year mortality was consistently achieved with immediate ART unless the rate of fatal ART toxicity was > 1.0/100 person-years, the rate of withdrawal from care was > 1.2-fold higher or the rate of ART failure due to poor adherence was > 4.3-fold higher on immediate than on WHO 2010 ART. In multi-way sensitivity analysis, immediate ART led to higher mortality when moderate rates of fatal ART toxicity (0.25/100 person-years) were combined with rates of withdrawal from care > 1.1-fold higher and rates of treatment failure > 2.1-fold higher on immediate than on WHO 2010 ART. Conclusions: In sub-Saharan Africa, ART initiation at entry into care would improve long-term survival of patients with high CD4(+) T-cell counts, unless it is associated with increased withdrawal from care and decreased adherence. In early ART trials, a focus on retention and adherence will be crucial.