Impact of Trimethoprim-Sulfamethoxazole and Chloroquine Prophylaxis on Drug-Resistant Plasmodium falciparum Mutations in Adults with HIV in Malawi

Drug resistance is a major obstacle for malaria control and elimination. Prophylactic antimalarial drug use may contribute to antimalarial drug resistance. We evaluated samples collected from a randomized, controlled clinical trial comparing chloroquine (CQ) with trimethoprim-sulfamethoxazole (TS) prophylaxis among adults with HIV on successful antiretroviral therapy in Malawi. We hypothesized that compared with no prophylaxis controls, participants receiving prophylaxis would have higher rates of polymorphisms associated with antifolate resistance in dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) for the TS group and higher rates of the chloroquine resistance transporter (pfcrt) for the CQ group. Pyrosequencing of these key molecular markers revealed no significant differences in resistance mutation prevalence across treatment arms. Compared with those infecting controls, parasites infecting those receiving TS or CQ prophylaxis did not have increased prevalence of resistance-associated polymorphisms in pfdhfr, pfdhps, and pfcrt. Importantly, we did not detect a mutation indicating CQ resistance in any breakthrough infection.