Clinical predictors and incidence of Kaposi sarcoma among males with HIV in the Treat-all era in the United States and Canada

Background Stagnating declines in Kaposi sarcoma (KS) among men with HIV (MWH) following Treat-All policies necessitate evaluating changes in clinical drivers of KS. We examined clinical factors and their associations with KS rates among MWH in North America. Methods Among MWH in the North American AIDS Cohort Collaboration on Research and Design, we estimated annual KS rates (per 100,000 person-years [PY]) by viral suppression (<200 copies/mL), CD4 count (<500 vs. ≥500 cells/mm3) and time since ART initiation (<1 year/naïve vs. ≥ 1 year) from 2009-2019. We quantified associations between clinical factors and KS rates using negative binomial regression, estimating incidence rate ratios with 95% confidence intervals (IRR, 95% CI). Among MWH with KS, we estimated average annual percent changes (AAPC) in clinical factor distribution using joinpoint regression. Results There were 61,155 MWH (370,624 PY) contributing 262 KS diagnoses. KS declined from 132-43 cases per 100,000 PY between 2009-2019. Viral suppression (IRR2009: 0.09 [95% CI 0.04, 0.20]; IRR2019: 0.69 [0.31, 1.54], recent/no ART initiation (IRR2009: 0.14 [0.07, 0.30]; IRR2019: 1.16 [0.53, 2.56]), and CD4 count ≥500 cells/mm3 (IRR2009: 0.13 [0.05, 0.31]; IRR2019: 0.44 [0.18, 1.10]) were associated with reduced KS rates, attenuating over time. Unsuppressed viral load at KS diagnosis declined 10.6% (-15.8%, -4.8%) as did those on ART ≤1 year/naïve (70%-40% [AAPC:-6.3% (-13.8%, 2.1%)]). Conclusions Our findings underscore the importance of early HIV diagnosis/treatment in reducing KS burden. Attenuating associations with HIV factors indicate that those successfully managing HIV increasingly represent KS patients. KS drivers are evolving, requiring patient/population-level monitoring.