Mulinda Nyirenda1, McNeil Ngongondo2, Minhee Kang3, Triin Umbleja3, Susan E Krown4, Catherine Godfrey5, Wadzanai Samaneka6, Rosie Mngqibisa7, Brenda Hoagland8, Noluthando Mwelase9, Stephanie Caruso10, Oto Martinez-Maza11, Dirk P Dittmer12, Margaret Borok6, Mina C Hosseinipour2,12, Thomas B Campbell13. 1. Johns Hopkins Project, University of Malawi College of Medicine, Blantyre, Malawi. 2. UNC Project Malawi, Lilongwe, Malawi. 3. Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA. 4. AIDS Malignancy Consortium, New York, NY. 5. Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. 6. Department of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe. 7. Durban International Clinical Research Site, Enhancing Care Foundation, Durban, South Africa. 8. Oswaldo Cruz Foundation, Evandro Chagas National Institute of Infectious Diseases, Rio de Janeiro, Brazil. 9. University of Witwatersrand, Johannesburg, South Africa. 10. Frontier Science Foundation, Amherst, New York, NY. 11. Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA. 12. Department of Microbiology & Immunology, University of North Carolina School of Medicine, and Lineberger Comprehensive Cancer Center, Chapel Hill, NC; and. 13. Department of Medicine/Division of Infectious Diseases, University of Colorado School of Medicine, Aurora, CO.
Abstract
BACKGROUND: Early progression of AIDS-associated Kaposi sarcoma (KS-PD) and immune reconstitution inflammatory syndrome (KS-IRIS) sometimes occur after the initiation of antiretroviral therapy (ART). METHODS: Early KS-PD and KS-IRIS were assessed in the A5264/AMC-067 trial in which participants with mild-to-moderate AIDS-KS were randomized to initiate ART with either immediate or as-needed oral etoposide. Early KS-PD was defined as tumor progression within 12 weeks of ART initiation. When investigators had concern that early KS-PD was KS-IRIS, additional evaluations were performed. Suspected KS-IRIS was defined as early KS-PD accompanied by a CD4 count increase of ≥50 cells per cubic millimeter or plasma HIV-1 RNA decrease of ≥0.5 log10 copies/mL. Clinical outcome was a composite end point categorized as failure, stable, and response at 48 and 96 weeks compared with baseline. RESULTS: Fifty of 190 participants had early KS-PD (27%): 28 had KS-IRIS and 22 were not evaluated for KS-IRIS. Early KS-PD and KS-IRIS incidences with immediate etoposide versus ART alone were 16% versus 39%, and 7% versus 21%, respectively. Week 48 clinical outcome was 45% failure, 18% stable, and 37% response for no early KS-PD; 82% failure, 2% stable, and 16% response for early KS-PD; and 88% failure, 0% stable, and 12% response for KS-IRIS. Cumulative incidence of KS tumor response by week 96 was 64% for no early KS-PD, 22% with early KS-PD, and 18% with KS-IRIS. CONCLUSIONS: Early KS-PD, including suspected KS-IRIS, was common after starting ART for AIDS-KS and was associated with worse long-term clinical outcomes. Starting ART concurrently with etoposide reduced the incidence of both early KS-PD and KS-IRIS compared with ART alone.
BACKGROUND: Early progression of AIDS-associated Kaposi sarcoma (KS-PD) and immune reconstitution inflammatory syndrome (KS-IRIS) sometimes occur after the initiation of antiretroviral therapy (ART). METHODS: Early KS-PD and KS-IRIS were assessed in the A5264/AMC-067 trial in which participants with mild-to-moderate AIDS-KS were randomized to initiate ART with either immediate or as-needed oral etoposide. Early KS-PD was defined as tumor progression within 12 weeks of ART initiation. When investigators had concern that early KS-PD was KS-IRIS, additional evaluations were performed. Suspected KS-IRIS was defined as early KS-PD accompanied by a CD4 count increase of ≥50 cells per cubic millimeter or plasma HIV-1 RNA decrease of ≥0.5 log10 copies/mL. Clinical outcome was a composite end point categorized as failure, stable, and response at 48 and 96 weeks compared with baseline. RESULTS: Fifty of 190 participants had early KS-PD (27%): 28 had KS-IRIS and 22 were not evaluated for KS-IRIS. Early KS-PD and KS-IRIS incidences with immediate etoposide versus ART alone were 16% versus 39%, and 7% versus 21%, respectively. Week 48 clinical outcome was 45% failure, 18% stable, and 37% response for no early KS-PD; 82% failure, 2% stable, and 16% response for early KS-PD; and 88% failure, 0% stable, and 12% response for KS-IRIS. Cumulative incidence of KS tumor response by week 96 was 64% for no early KS-PD, 22% with early KS-PD, and 18% with KS-IRIS. CONCLUSIONS: Early KS-PD, including suspected KS-IRIS, was common after starting ART for AIDS-KS and was associated with worse long-term clinical outcomes. Starting ART concurrently with etoposide reduced the incidence of both early KS-PD and KS-IRIS compared with ART alone.
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