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

J Acquir Immune Defic Syndr. 2020 Aug 1;84(4):422-429. doi: 10.1097/QAI.0000000000002361.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Africa South of the Sahara
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • CD4 Lymphocyte Count
  • Disease Progression
  • Etoposide / therapeutic use
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / chemically induced*
  • Immune Reconstitution Inflammatory Syndrome / pathology
  • Male
  • Sarcoma, Kaposi / drug therapy*
  • Sarcoma, Kaposi / pathology
  • South America
  • Treatment Outcome


  • Anti-HIV Agents
  • Antineoplastic Agents, Phytogenic
  • Etoposide