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Plasmodium falciparum Dihydrofolate Reductase and Dihyropteroate Synthase Mutations and the Use of Trimethoprim-Sulfamethoxazole Prophylaxis among Persons Infected with Human Immunodeficiency Virus

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  • Global AIDS Program, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention–Uganda, Entebbe, Uganda; Department of Medicine, University of Washington School of Medicine, Seattle, Washington; Division of Epidemiology, School of Public Health, University of California, Berkeley, California; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Coordinating Office for Global Health,Centers for Disease Control and Prevention–Kenya, Nairobi, Kenya

A prospective cohort design was used to measure the association between daily cotrimoxazole-prophylaxis and infection with Plasmodium falciparum containing mutations associated with antifolate resistance among persons infected with human immunodeficiency virus (HIV) in Tororo and Busia District, in eastern Uganda. Of 149 cases of P. falciparum parasitemia diagnosed, 147 (99%) (smears from participants taking prophylaxis = 91 and smears from those not taking cotrimoxazole prophylaxis = 56) were successfully assessed for mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations associated with antifolate resistance. Prevalences of the dhfr pure triple mutant (74% and 70%; P = 0.71), the dhps pure double mutant (95% and 88%; P = 0.21), and the dhfr/dhps pure quintuple mutant (73% and 64%; P = 0.36), were not significantly different between those taking and those not taking cotrimoxazole-prophylaxis, respectively. The overall prevalence of the pure quintuple mutant in this study was 69%, which is among the highest in Africa. Although resistance rates of P. falciparum to antifolate drugs are high, cotrimoxazole-prophylaxis in HIV-infected persons was not associated with a higher prevalence of mutations associated with antifolate resistance.

Author Notes

*Address correspondence to Samuel Malamba, Global AIDS Program, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention–Uganda, c/o Uganda Virus Research Institute, PO Box 49, Entebbe, Uganda. E-mails: malambas@gmail.com or zcq2@ug.cdc.gov

Financial support: This study was supported by CDC and the United States Agency for International Development through the Emergency Plan for AIDS Relief. Samuel Malamba was supported by the Fogarty AIDS International Training and Research Program (1-D43-TW00003) at the University of California, Berkeley. Testing for molecular markers was supported by the Fogarty International Center/National Institutes of Health (TW00007).

Authors' addresses: Samuel Malamba and John Lule, Global AIDS Program, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention–Uganda, Entebbe, Uganda. Taylor Sandison, Department of Medicine, University of Washington School of Medicine, Seattle, WA. Arthur Reingold, Division of Epidemiology, School of Public Health, University of California, Berkeley, CA. Jordan Walker and Grant Dorsey, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA. Jonathan Mermin, Coordinating Office for Global Health, Centers for Disease Control and Prevention–Kenya, Nairobi, Kenya.

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