Background: Clinical trials are not well suited to evaluate the effectiveness and cost-effectiveness of interventions in “real world” settings. Using a quasi-experimental regression-discontinuity design (Bor et al. 2014), we establish the causal effect of early (vs. deferred) ART initiation on patient survival in rural South Africa, and obtain empirical (as opposed to modeled) cost-effectiveness estimates. Methods: Demographic data from a large population surveillance in rural KwaZulu-Natal were linked to clinical records from the public sector ART program. 4391 patients enrolled in HIV care between 2007 and 2011. CD4 counts were collected upon entry into care regardless of ART initiation. Subjects were eligible for ART if CD4 < 200 cells/μL, as per national guidelines. Dates of death were obtained from the demographic surveillance; dates of initiation and follow-up CD4 counts were obtained from clinical records. Patients were followed for up to five years. We estimated the causal effect of immediate ART eligibility on survival, immune health, and time spent in pre-ART and on ART, which were used to estimate costs. Effects were estimated using a regression-discontinuity design, which exploits the quasi-random nature of treatment assignment for patients with first CD4 counts close to the eligibility threshold. Patients just above vs. just below the threshold are similar on all observed and unobserved factors; but they receive different treatment assignments. Results: Patients presenting with a CD4+ count just below 200 cells/μL were 4.3% points (95% CI 0.6, 8.0) more likely to be alive at two years than patients presenting with a CD4+ count just above the cut-off, an advantage that persisted at five years (Fig 1). These effects imply a 14.9% point two-year survival advantage for patients who actually initiated ART because they had an eligible CD4+ count. Large, persistent gains in clinical immune function were also observed among patients who were ART eligible. The additional medical care provided to ART-eligible patients implied a cost of $1967 per life year saved to treating patients with CD4+ counts close to 200-cells over a five-year horizon. Conclusions: In a real-world setting, referral of patients to pre-ART care (vs. immediate ART eligibility) led to large losses of life and health. These losses could have been avoided with immediate ART, which was found to be “very cost effective” at conventional benchmarks.
Conference: CROI 2015, Seattle, Washington, USA