Title: Programmatic and Individual-level Factors Associated with CD4 Cell Count at HAART Initiation and Survival Among Treatment-naïve Patients Initiating HAART in sub-Saharan Africa
Description: People living with HIV in low- and middle-income countries, on average, initiate antiretroviral therapy (ART) in the advanced stages of the infection (i.e. when the CD4 cell count has dropped below the recommended threshold for ART initiation) despite more than a decade since the start of scale-up of ART [1-4]. Late ART initiation is associated with higher patient morbidity and mortality, increased risk of secondary transmission in the population and higher healthcare cost [5-10]. Knowledge of HIV status is a critical first step to initiate ART [11-14]. Yet, half of the people living with HIV in sub-Saharan Africa are not aware of their status [15]. The World Health Organization, the Joint United Nations Programme on HIV/AIDS and other institutions support adoption of active screening for HIV (i.e. testing asymptomatic people for HIV) to help identify and treat people living with HIV before progressing to the advanced stages of the infection [11, 14, 16, 17]. The role of active screening on earlier initiation of ART and patient survival has not been examined.

In this dissertation, I reviewed and synthesized the literature to identify barriers to ART initiation operating in low- and middle-income countries. I examined the role of active screening on patient CD4 cell count at ART initiation (a measure of HIV-disease progression) and survival, and investigated patient CD4 cell count at ART initiation as a potential mediator of the active screening-patient survival association. The databases Ovid Medline, PsycINFO, CINAHL, Scopus and Cochrane Reviews were searched as part of the literature review. Of 265 articles reviewed, thirty-five met the eligibility criteria and were therefore selected for the review. Mixed linear regression models with random intercepts and Marginal Cox Proportional models with robust sandwich estimators of variance were fitted as part of the statistical analyses for this dissertation. Patient, programmatic, and contextual variables were considered for statistical adjustment. Data for the analyses came from twenty-nine HIV/AIDS care and treatment sites in Kenya, Uganda, and Tanzania participating in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) initiative.

Patient level data were collected from 45,359 subjects who initiated ART between 2003 and 2008 in the twenty-nine sites. Site programmatic and contextual level data were collected via two structured questionnaires. The critical review of the literature led to the identification of 1) individual, programmatic and societal-level barriers to HIV testing, enrolling into care, and ART initiation; and 2) barriers pertaining to lack of knowledge of HIV/AIDS and ART (e.g. HIV/AIDS symptomatology, ART benefits, ART toxicity), limited accessibility to services, poor quality of services, shortage of staff, and HIV-related stigma as the most prominent barriers. Results of the analyses show that patients in sites with predominantly "Active Screening Entry Points" initiated ART, on average, with CD4 cell counts 24 cells/µL higher than patients in sites with mainly "non-Active Screening Entry Points." However, the gain in CD4 cell count did not translate into a statistically significant estimate of survival advantage for these patients [HR (95% CI): 0.82 (0.64 - 1.06)] though the results are in the expected directions.

The modest gain in mean CD4 cell count, and the documented benefits of active screening (e.g. high acceptability, increased number of patients tested and higher rate of identification of previously undiagnosed people living with HIV) support adoption of this intervention particularly in regions with a high HIV burden and where a low proportion of the population is unaware of their HIV status.