Oversight Committee for the Evaluation of Metabolic Complications of HAART, with representatives from academia, patient community, US Food and Drug Administration, European Medicines Agency and consortium of AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, Merck, Pfizer, F Hoffmann-La Roche, and Janssen Pharmaceuticals.

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Efforts to scale-up HIV care and treatment have been successful at initiating large numbers of patients onto antiretroviral therapy (ART), although persistent challenges remain to optimizing scale-up effectiveness in both resource-rich and resource-limited settings. Among the most important are very high rates of ART initiation in the advanced stages of HIV disease, which in turn drive morbidity, mortality, and onward transmission of HIV. With a focus on sub-Saharan Africa, this review article presents a conceptual framework for a broader discussion of the persistent problem of late ART initiation, including a need for more focus on the upstream precursors (late HIV diagnosis and late enrollment into HIV care) and their determinants. Without additional research and identification of multilevel interventions that successfully promote earlier initiation of ART, the problem of late ART initiation will persist, significantly undermining the long-term impact of HIV care scale-up on reducing mortality and controlling the HIV epidemic.

Objective In sub-Saharan Africa, many patients initiate antiretroviral therapy (ART) at CD4+ cell counts much lower than those recommended in national guidelines. We examined program-level and contextual-level factors associated with low median CD4+ cell count at ART initiation in populations initiating ART. Design Multilevel analysis of aggregate and program-level service delivery data. Methods We examined data on 1690 cohorts of patients initiating ART during 2004–2008 in eight sub-Saharan African countries. Cohorts with median CD4+ less than 111 cells/μl (the lowest quartile) were classified as having low median CD4+ cell count at ART initiation. Cohort information was combined with time-updated program-level data and subnational contextual-level data, and analyzed using multilevel models. Results The 1690 cohorts had median CD4+ cell count of 136 cells/μl and included 121 504 patients initiating ART at 267 clinics. Program-level factors associated with low cohort median CD4+ cell count included urban setting [adjusted odds ratio (AOR) 2.1; 95% confidence interval (CI) 1.3–3.3], lower provider-to-patient ratio (AOR 2.2; 95% CI 1.3–4.0), no PMTCT program (AOR 3.6; 95% CI 1.0–12.8), outreach services for ART patients only vs. both pre-ART and ART patients (AOR 2.4; 95% CI 1.5–3.9), fewer vs. more adherence support services (AOR 1.6; 95% CI 1.0–2.5), and smaller cohort size (AOR 2.5; 95% CI 1.4–4.5). Contextual-level factors associated with low cohort median CD4+ cell count included initiating ART in areas where a lower proportion of the population heard of AIDS, tested for HIV recently, and a higher proportion believed ‘limiting themselves to one HIV-uninfected sexual partner reduces HIV risk’. Conclusion Determinants of CD4+cell count at ART initiation in populations initiating ART operate at multiple levels. Structural interventions targeting points upstream from ART initiation along the continuum from infection to diagnosis to care engagement are needed.