Impact of Protease Inhibitors on HIV-Associated Kaposi Sarcoma Incidence: A Systematic Review

BACKGROUND: Protease inhibitors (PIs) may inhibit Kaposi sarcoma (KS) carcinogenesis. However, PI-based antiretroviral therapy (ART) is rarely a first-line choice in people living with HIV (PLWH) because of cost and toxicities. This is the first systematic review to assess KS incidence stratified by ART type. METHODS: We searched PubMed to identify original, full research reports of KS incidence in ART-treated adult PLWH, stratified by ART class, published between 1996 and 2017. For overlapping cohorts, we included only the most recent study and supplemented data with earlier relevant analyses. We described study design, sociodemographic characteristics, statistical adjustment factors, and KS incidence. RESULTS: We identified three unique retrospective cohort studies, and supplemented one of the studies with results from six prior subgroup reports, which included 242,309 PLWH and 3570 incident KS cases. Overall, KS crude incidence decreased by a factor of 10 between untreated and ART-treated PLWH; CD4-adjusted KS incidence decreased by ~50%, with either non-nucleoside reverse transcriptase inhibitor (NNRTI)- or PI-based ART. A single study measured a cumulative dose-/time-dependent effect of ART, which reported a relative risk reduction in only the cohort receiving boosted PI-based ART. Other studies defined ART categories by first-line therapy only. CONCLUSIONS: The risk of incident KS was significantly reduced regardless of ART class even after adjusting for CD4 count. The quality of evidence (i.e., most studies categorizing users by first-line ART) does not permit KS risk reduction comparisons across ART types. Given the limited number and retrospective nature of these studies, prospective data is indicated.