Impact of increasing CD4 count threshold eligibility for antiretroviral therapy initiation on advanced HIV disease and tuberculosis prevalence and incidence in South Africa: an interrupted time series analysis

Abstract

AbstractIntroductionWe investigated the impact of increasing CD4 count eligibility for antiretroviral-therapy (ART) initiation on advanced HIV and tuberculosis (TB) prevalence and incidence among people living with HIV (PLHIV) in South Africa.MethodsWe conducted an interrupted time series analysis with de-identified data of PLHIV aged ≥15 initiating ART between April-2012 and February-2020 at 65 primary healthcare clinics in KwaZulu-Natal, South Africa. Outcomes included monthly proportions of new ART initiators presenting with advanced HIV (CD4 count <200 cells/µl) and TB disease. We created a cohort of monthly ART initiators without TB and evaluated the cumulative incidence of TB within 12 months follow-up. We used segmented binomial regression models to estimate relative risks (RR) of outcomes, allowing for a step and slope change after expanding the ART initiation CD4 count eligibility from <350 to <500 cells/µl in January- 2015 and following Universal-Test-and-Treat (UTT) implementation in September-2016.ResultsAmong 187,544 participants, median age was 32 (27-39), and 125,065 (66.7%) were female. After January-2015, risk of advanced HIV at initiation decreased by 24.5% (RR=0.745, 95%CI 0.690-0.800) and further reduced by 26.2% following UTT implementation (RR=0.738, 95%CI 0.688-0.788). Risk of TB at initiation also decreased by 28.7% after January-2015 (RR=0.713, 95%CI 0.644-0.782) and further decreased by 17.6% after UTT implementation (RR=0.824, 95%CI 0.703-0.945) but remained stable among initiators with advanced HIV. Among the incidence cohort, the risk of new TB decreased by 31.9% (RR=0.681, 95%CI 0.441-0.921) following UTT implementation. Among the incidence cohort with advanced HIV, there was weak evidence of a decrease in risk of new TB (RR=0.755, 95%CI 0.489-1.021), but it gradually decreased per month (slope change per month 9.7%, RR=0.903, 95%CI 0.872-0.934) following UTT implementation.ConclusionsOur data supports the added benefit of decreased TB co-burden with expanded ART access. Early diagnosis and immediate linkage to care should be prioritised among PLHIV.