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.

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.

• Authors: Mulinda Nyirenda, McNeil Ngongondo, Minhee Kang, Triin Umbleja, Susan E Krown, Catherine Godfrey, Wadzanai Samaneka, Rosie Mngqibisa, Brenda Hoagland, Noluthando Mwelase, Stephanie Caruso, Oto Martinez-Maza, Dirk P Dittmer, Margaret Borok, Mina C Hosseinipour, Thomas B Campbell, A5264/AMC-067 team
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 84 Issue 4 Pg. 422-429 (08 01 2020) ISSN: 1944-7884 [Electronic] United States
• PMID: 32265361 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

• Adult
• Africa South of the Sahara
• Anti-HIV Agents (adverse effects, 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, pathology)
• Male
• Sarcoma, Kaposi (drug therapy, pathology)
• South America
• Treatment Outcome