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Impact of Protease Inhibitors on HIV-Associated Kaposi Sarcoma Incidence

A Systematic Review

Chang, Elaine, MD*,†; Mapakshi, Srikar R., MD*; Mbang, Pamela, MD; El-Mallawany, Nader Kim, MD§; Kramer, Jennifer R., MPH, PhD*,║,¶; White, Donna L., MPH, PhD*,║,¶,#; Chiao, Elizabeth Y., MPH, MD*,║,**

JAIDS Journal of Acquired Immune Deficiency Syndromes: October 1, 2018 - Volume 79 - Issue 2 - p 141–148
doi: 10.1097/QAI.0000000000001798
Critical 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 3 unique retrospective cohort studies, and supplemented one of the studies with results from 6 previous 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– 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 (ie, 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 are indicated.

*Center for Innovation, Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX;

Section of Hematology & Oncology, Department of Medicine, Baylor College of Medicine, Houston, TX;

Cape Fear Valley Medical Center, Fayetteville, NC;

§Department of Pediatrics, Baylor College of Medicine, Houston, TX;

Cancer Prevention and Population Sciences, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston;

Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX;

#Center for Translational Research in Infectious Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX; and

**Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX.

Correspondence to: Elizabeth Y. Chiao, MD, Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston VA Medical Center (152), 2002 Holcombe Blvd, Houston, TX 77030 (e-mail:

Supported by the VA Health Services Research & Development Center of Innovation grant CIN 13-413. NIH grant 1R01 CA206476. NIH grant T32 CA174647. AIDS Malignancy Consortium grant 2U01CA121947-04. P30 CA125123 (Dan L Duncan Comprehensive Cancer Center). Dr. White receives salary support from the U.S. Department of Veterans Affairs Clinical Science Research and Development program (CX001430).

The authors have no funding or conflicts of interest to disclose.

D.L.W. and E.Y.C. contributed equally as senior authors.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received March 16, 2018

Accepted June 07, 2018

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.