title: Does cotrimoxazole prophylaxis for the prevention of HIV-associated opportunistic infections select for resistant pathogens in Kenyan adults?
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/muL (lower-CD4; N = 692) received cotrimoxazole; HIV-positive with CD4 cell count > or = 350 cells/muL (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.
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA. mhamel@ke.cdc.gov
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Hamel
authors.forename: Carolyn
authors.initials: C
authors.lastname: Greene
authors.forename: Tom
authors.initials: T
authors.lastname: Chiller
authors.forename: Peter
authors.initials: P
authors.lastname: Ouma
authors.forename: Christina
authors.initials: C
authors.lastname: Polyak
authors.forename: Kephas
authors.initials: K
authors.lastname: Otieno
authors.forename: John
authors.initials: J
authors.lastname: Williamson
authors.forename: Ya Ping
authors.initials: YP
authors.lastname: Shi
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Feikin
authors.forename: Barbara
authors.initials: B
authors.lastname: Marston
authors.forename: John T
authors.initials: JT
authors.lastname: Brooks
authors.forename: Amanda
authors.initials: A
authors.lastname: Poe
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhou
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ochieng
authors.forename: Eric
authors.initials: E
authors.lastname: Mintz
authors.forename: Laurence
authors.initials: L
authors.lastname: Slutsker
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000962:Antimalarials / Q000494:pharmacology; D015331:Cohort Studies; D004351:Drug Resistance; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007630:Kenya; D016778:Malaria, Falciparum / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects; D011446:Prospective Studies; D013296:Streptococcus pneumoniae / Q000187:drug effects; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000962:Antimalarials; D015662:Trimethoprim, Sulfamethoxazole Drug Combination