Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya

Background

Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organization (WHO) for HIV-1-infected individuals in settings with high infectious disease prevalence. The WHO 2006 guidelines were developed prior to the scale-up of antiretroviral therapy (ART). The threshold for CTX discontinuation following ART is undefined in resource-limited settings.

Methods and Findings

Between 1 February 2012 and 30 September 2013, we conducted an unblinded non-inferiority randomized controlled trial of CTX prophylaxis cessation versus continuation among HIV-1-infected adults on ART for ≥18 mo with CD4 count > 350 cells/mm³ in a malaria-endemic region in Kenya. Participants were randomized and followed up at 3-mo intervals for 12 mo. The primary endpoint was a composite of morbidity (malaria, pneumonia, and diarrhea) and mortality. Incidence rate ratios (IRRs) were estimated using Poisson regression.

Among 538 ART-treated adults screened, 500 were enrolled and randomized, 250 per arm. Median age was 40 y, 361 (72%) were women, and 442 (88%) reported insecticide-treated bednet use. Combined morbidity/mortality was significantly higher in the CTX discontinuation arm (IRR = 2.27, 95% CI 1.52–3.38; p < 0.001), driven by malaria morbidity. There were 34 cases of malaria, with 33 in the CTX discontinuation arm (IRR = 33.02, 95% CI 4.52–241.02; p= 0.001). Diarrhea and pneumonia rates did not differ significantly between arms (IRR = 1.36, 95% CI 0.82–2.27, and IRR = 1.43, 95% CI 0.54–3.75, respectively). Study limitations include a lack of placebo and a lower incidence of morbidity events than expected.

Conclusions

CTX discontinuation among ART-treated, immune-reconstituted adults in a malaria-endemic region resulted in increased incidence of malaria but not pneumonia or diarrhea. 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. These data support the 2014 WHO CTX guidelines.

Below:  Incidence of malaria cases in CTX discontinuation arm

Full article at:   http://goo.gl/ZbNU4N

By:  

Christina S. Polyak

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

Christina S. Polyak, Judd Walson, Barbra A. Richardson, Grace John-Stewart

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

Krista Yuhas, Judd Walson, Barbra A. Richardson, Grace John-Stewart

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

Benson Singa, Monica Khaemba

Kenya Medical Research Institute, Nairobi, Kenya

Judd Walson, Grace John-Stewart

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

Barbra A. Richardson

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

Grace John-Stewart

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

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