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.
Asare K., Lewis L., van der Molen J., Sookrajh Y., Khubone T., Ngwenya T., Mkhize NS., Lessells RJ., Naidoo K., Sosibo P., Bottomley C., Garrett N., Dorward J.
INTRODUCTION: We investigated the impact of increasing CD4 count eligibility for antiretroviral therapy (ART) initiation on advanced HIV disease (AHD) and tuberculosis (TB) prevalence and incidence among people living with HIV (PLHIV) in South Africa. METHODS: We conducted an interrupted time series analysis with de-identified data of PLHIV aged ≥15 years 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 AHD (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. RESULTS: Among 209 984 participants, median age was 32 (range: 26-38), and 141 499 (67.4%) were female. After January 2015, the risk of AHD at initiation decreased in step by 25.0% (RR=0.750, 95% CI 0.688 to 0.812) and further reduced by 26.9% following UTT implementation (RR=0.731, 95% CI 0.681 to 0.781). The risk of TB at initiation also decreased in step by 27.6% after January 2015 (RR=0.724, 95% CI 0.651 to 0.797) and further decreased by 17.4% after UTT implementation (RR=0.826, 95% CI 0.711 to 0.941) but remained stable among initiators with AHD. Among the incidence cohort, we saw a step decrease in the risk of new TB by 31.4% (RR=0.686, 95% CI 0.465 to 0.907) following UTT implementation. Among the incidence cohort with AHD, there was weak evidence of a step decrease in the risk of new TB (RR=0.755, 95% CI 0.489 to 1.021), but the slope decreased by 9.7% per month (RR=0.903, 95% CI 0.872 to 0.934) following UTT implementation. CONCLUSIONS: Our data support the added benefit of decreased TB co-burden with expanded ART access. Early diagnosis and immediate linkage to care should be prioritised among PLHIV.