As-needed vs immediate etoposide chemotherapy in combination with antiretroviral therapy for mild-to-moderate AIDS-associated kaposi sarcoma in resource-limited settings: A5264/AMC-067 randomized clinical trial

for the A5264/AMC-067 REACT-KS Team

Research output: Contribution to journalArticle

Abstract

Background Mild-to-moderate AIDS-associated Kaposi sarcoma (KS) often responds to antiretroviral therapy (ART) alone; the role of chemotherapy is unclear. We assessed the impact of immediate vs as-needed oral etoposide (ET) among human immunodeficiency virus (HIV)-infected individuals with mild-to-moderate KS initiating ART. Methods Chemotherapy-naive, HIV type 1-infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) alone (chemotherapy "as-needed" arm) vs ART plus up to 8 cycles of oral ET (immediate arm). Participants with KS progression on ART alone received ET as part of the as-needed strategy. Primary outcome was ordinal as follows: failure, stable, and response at 48 weeks. Secondary outcomes included time to initial KS progression, KS-associated immune reconstitution inflammatory syndrome (KS-IRIS), and KS response. Results Of 190 randomized participants (as-needed = 94, immediate = 96), the majority were men (71%) and African (93%). Failure (53.8% vs 56.6%), stable (16.3% vs 10.8%), and response (30% vs 32.5%) did not differ between arms (as-needed vs immediate) among those with week 48 data potential (N = 163, P =.91). Time to KS progression (P =.021), KS-IRIS (P =.003), and KS response (P =.003) favored the immediate arm. Twenty-five participants died (13%). Mortality, adverse events, CD4+ T-cell changes, and HIV RNA suppression were similar at 48 weeks. Conclusions Among HIV-infected adults with mild-to-moderate KS, immediate ET provided early, nondurable clinical benefits. By 48 weeks, no clinical benefit was observed compared to use of ET as needed. Mortality was high and tumor response was low. Clinical Trials Registration NCT01352117.

Original languageEnglish (US)
Pages (from-to)251-260
Number of pages10
JournalClinical Infectious Diseases
Volume67
Issue number2
DOIs
StatePublished - Jul 2 2018

Keywords

  • HIV
  • Kaposi sarcoma
  • antiretroviral therapy
  • chemotherapy
  • etoposide

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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