Does cotrimoxazole prophylaxis for the prevention of HIV-associated opportunistic infections select for resistant pathogens in Kenyan adults?

Mary J. Hamel, Carolyn Greene, Tom Chiller, Peter Ouma, Christina Polyak, Kephas Otieno, John Williamson, Ping Shi Ya, Daniel Feikin, Barbara Marston, John T. Brooks, Amanda Poe, Zhiyong Zhou, Benjamin Ochieng, Eric Mintz, Laurence Slutsker

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Abstract

We assessed the effect of daily cotrimoxazole, essential for HIV care, on development of antifolate-resistant Plasmodium falciparum, naso-pharyngeal Streptococcus pneumoniae (pneumococcus), and commensal Escherichia coli. HIV-positive subjects with CD4 cell count < 350 cells/μL (lower-CD4; N = 692) received cotrimoxazole; HIV-positive with CD4 cell count ≥ 350 cells/μL (higher-CD4; N = 336) and HIV-negative subjects (N = 132) received multivitamins. Specimens were collected at baseline, 2 weeks, monthly, and at sick visits during 6 months of follow-up to compare changes in resistance, with higher-CD4 as referent. P. falciparum parasitemia incidence density was 16 and 156/100 person-years in lower-CD4 and higher-CD4, respectively (adjusted rate ratio [ARR] = 0.11; 95% confidence interval [CI] = 0.06-0.15; P < 0.001) and 97/100 person-years in HIV-negative subjects (ARR = 0.62; 95% CI = 0.44-0.86; P = 005). Incidence density of triple and quintuple dihydrofolate-reductase/ dihydropteroate-synthetase mutations was 90% reduced in lower-CD4 compared with referent. Overall, cotrimoxazole non-susceptibility was high among isolated pneumococcus (92%) and E. coli (76%) and increased significantly in lower-CD4 subjects by Week 2 (P < 0.005). Daily cotrimoxazole prevented malaria and reduced incidence of antifolate-resistant P. falciparum but contributed to increased pneumococcus and commensal Escherichia coli resistance.

Original languageEnglish (US)
Pages (from-to)320-330
Number of pages11
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume79
Issue number3
Publication statusPublished - Sep 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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