HIV/AIDS management: Trial shows importance of cotrimoxazole prophylaxis in malaria-endemic regions

January 05, 2016

Randomized trial in Kenya demonstrates importance of cotrimoxazole prophylaxis for HIV/AIDS management in malaria-endemic regions

Cotrimoxazole (CTX) discontinuation is inferior to CTX continuation among ART-treated, immune-reconstituted HIV-infected adults living in a malaria-endemic region, according to a trial published this week in PLOS Medicine by Christina Polyak at the Walter Reed Army Institute of Research and University of Washington, U.S., and colleagues. These trial findings were important for December 2014 WHO guidelines recommending that CTX prophylaxis be continued regardless of CD4 cell count or HIV/AIDS clinical stage in settings where malaria is endemic and/or severe bacterial infections are common.

The trial enrolled 500 HIV-infected adults living in a malaria-endemic region of Kenya who had been treated with ART for ?18 months, who had a CD4 count of >350 cells/mm3, and who were taking CTX. After 12 months of follow-up, the combined rate of morbidity events (malaria, pneumonia, and diarrhea) and non-trauma mortality events was significantly higher in the CTX discontinuation arm than in the CTX continuation arm (IRR = 2.27, 95% CI 1.52-3.38; p < 0.001). The difference in this primary outcome between the trial arms was driven by malaria morbidity -- there were 33 cases of malaria in the CTX discontinuation arm but only one case in the CTX continuation arm.

Study limitations included lack of blinding and statistical constraints from lower than expected incidence of morbidity. However, analyses were strengthened by 98% retention rates in both arms. The authors state, "Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence."

ClinicalTrials.gov NCT01425073
-end-
Research Article

Funding:

Supported by the Merle A. Sande Award in International Infectious Diseases, Infectious Disease Society of America (IDSA) and the Armed Forces Health Surveillance Center -- Department of Defense Global Emerging Infections System. Research reported in this publication was also supported by NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK of the National Institutes of Health under award number P30AI027757 and NICHD K24-HD054314 (G.J-S.). Vestergaard Frandsen donated insecticide treated bednets and water filters. Alere Inc. donated CD4 cartridges for Pima machines. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Competing Interests:

The authors have declared that no competing interests exist.

Citation:

Polyak CS, Yuhas K, Singa B, Khaemba M, Walson J, Richardson BA, et al. (2016) Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial. PLoS Med 13(1): e1001934. doi:10.1371/journal.pmed.1001934

Author Affiliations:

US Military HIV Research Program, Walter Reed Army Institute of Research, Bethesda, Maryland, United States of America

Department of Medicine, University of Washington, Seattle, Washington, United States of America

Department of Global Health, University of Washington, Seattle, Washington, United States of America

Kenya Medical Research Institute, Nairobi, Kenya

Department of Pediatrics, University of Washington, Seattle, Washington, United States of America

Department of Biostatistics, University of Washington, Seattle, Washington, United States of America

Department of Epidemiology, University of Washington, Seattle, Washington, United States of America

Contact:

Christina S Polyak
cpolyak@hivresearch.org
301-500-3688
U.S. Military HIV Research Program | HJF
6720-A Rockledge Drive
Bethesda, MD 20817
UNITED STATES

PLOS

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