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

Research output: Contribution to journalArticle

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
StatePublished - Sep 2008
Externally publishedYes

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Opportunistic Infections
Sulfamethoxazole Drug Combination Trimethoprim
Streptococcus pneumoniae
HIV
Plasmodium falciparum
Folic Acid Antagonists
CD4 Lymphocyte Count
Escherichia coli
Incidence
Dihydropteroate Synthase
Confidence Intervals
Tetrahydrofolate Dehydrogenase
Parasitemia
Malaria
Mutation

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Does cotrimoxazole prophylaxis for the prevention of HIV-associated opportunistic infections select for resistant pathogens in Kenyan adults? / Hamel, Mary J.; Greene, Carolyn; Chiller, Tom; Ouma, Peter; Polyak, Christina; Otieno, Kephas; Williamson, John; Ya, Ping Shi; Feikin, Daniel; Marston, Barbara; Brooks, John T.; Poe, Amanda; Zhou, Zhiyong; Ochieng, Benjamin; Mintz, Eric; Slutsker, Laurence.

In: American Journal of Tropical Medicine and Hygiene, Vol. 79, No. 3, 09.2008, p. 320-330.

Research output: Contribution to journalArticle

Hamel, MJ, Greene, C, Chiller, T, Ouma, P, Polyak, C, Otieno, K, Williamson, J, Ya, PS, Feikin, D, Marston, B, Brooks, JT, Poe, A, Zhou, Z, Ochieng, B, Mintz, E & Slutsker, L 2008, 'Does cotrimoxazole prophylaxis for the prevention of HIV-associated opportunistic infections select for resistant pathogens in Kenyan adults?', American Journal of Tropical Medicine and Hygiene, vol. 79, no. 3, pp. 320-330.
Hamel, Mary J. ; Greene, Carolyn ; Chiller, Tom ; Ouma, Peter ; Polyak, Christina ; Otieno, Kephas ; Williamson, John ; Ya, Ping Shi ; Feikin, Daniel ; Marston, Barbara ; Brooks, John T. ; Poe, Amanda ; Zhou, Zhiyong ; Ochieng, Benjamin ; Mintz, Eric ; Slutsker, Laurence. / Does cotrimoxazole prophylaxis for the prevention of HIV-associated opportunistic infections select for resistant pathogens in Kenyan adults?. In: American Journal of Tropical Medicine and Hygiene. 2008 ; Vol. 79, No. 3. pp. 320-330.
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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.",
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AU - Hamel, Mary J.

AU - Greene, Carolyn

AU - Chiller, Tom

AU - Ouma, Peter

AU - Polyak, Christina

AU - Otieno, Kephas

AU - Williamson, John

AU - Ya, Ping Shi

AU - Feikin, Daniel

AU - Marston, Barbara

AU - Brooks, John T.

AU - Poe, Amanda

AU - Zhou, Zhiyong

AU - Ochieng, Benjamin

AU - Mintz, Eric

AU - Slutsker, Laurence

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N2 - 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.

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