Does cotrimoxazole prophylaxis for the prevention of HIV-associated opportunistic infections select for resistant pathogens in Kenyan adults?
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.
Hamel
Mary J
MJ
Centers for Disease Control and Prevention, Atlanta, Georgia, USA. mhamel@ke.cdc.gov
Greene
Carolyn
C
Chiller
Tom
T
Ouma
Peter
P
Polyak
Christina
C
Otieno
Kephas
K
Williamson
John
J
Shi
Ya Ping
YP
Feikin
Daniel R
DR
Marston
Barbara
B
Brooks
John T
JT
Poe
Amanda
A
Zhou
Zhiyong
Z
Ochieng
Benjamin
B
Mintz
Eric
E
Slutsker
Laurence
L
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*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000962:Antimalarials; D015662:Trimethoprim, Sulfamethoxazole Drug Combination