Early progression and immune reconstitution inflammatory syndrome during treatment of mild-to-moderate Kaposi sarcoma in sub-Saharan Africa and South America: Incidence, long-term outcomes and effects of early chemotherapy.

BACKGROUND: Early progression of AIDS-associated Kaposi sarcoma (KS-PD) and immune reconstitution inflammatory syndrome (KS-IRIS) sometimes occur after 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 >/=50/mm or plasma HIV-1 RNA decrease >/=0.5 log10 copies/mL. Clinical outcome was a composite endpoint categorized as Failure, Stable and Response at 48 and 96 weeks compared to baseline. RESULTS: Fifty of 190 participants had early KS-PD (27%): 28 had KS-IRIS, 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/37% Response for no early KS-PD; 82% Failure/2% Stable/16% Response for early KS-PD; and 88% Failure/0% Stable/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. CONCLUSION: 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 to ART alone.