Impact of daily cotrimoxazole on clinical malaria and asymptomatic parasitemias in HIV-exposed, uninfected infants

Clin Infect Dis. 2015 Aug 1;61(3):368-74. doi: 10.1093/cid/civ309. Epub 2015 Apr 21.


Background: Cotrimoxazole preventive therapy (CPT) is recommended for all human immunodeficiency virus (HIV)-exposed infants to avoid opportunistic infections. Cotrimoxazole has antimalarial effects and appears to reduce clinical malaria infections, but the impact on asymptomatic malaria infections is unknown.

Methods: We conducted an observational cohort study using data and dried blood spots (DBSs) from the Breastfeeding, Antiretrovirals and Nutrition study to evaluate the impact of CPT on malaria infection during peak malaria season in Lilongwe, Malawi. We compared malaria incidence 1 year before and after CPT implementation (292 and 682 CPT-unexposed and CPT-exposed infants, respectively), including only infants who remained HIV negative by 36 weeks of age. Malaria was defined as clinical, asymptomatic (using DBSs at 12, 24, and 36 weeks), or a composite outcome of clinical or asymptomatic. Linear and binomial regression with generalized estimating equations were used to estimate the association between CPT and malaria. Differences in characteristics of parasitemias and drug resistance polymorphisms by CPT status were also assessed in the asymptomatic infections.

Results: CPT was associated with a 70% (95% confidence interval, 53%-81%) relative reduction in the risk of asymptomatic infection between 6 and 36 weeks of age. CPT appeared to provide temporary protection against clinical malaria and more sustained protection against asymptomatic infections, with no difference in parasitemia characteristics.

Conclusions: CPT appears to reduce overall malaria infections, with more prolonged impacts on asymptomatic infections. Asymptomatic infections are potentially important reservoirs for malaria transmission. Therefore, CPT prophylaxis may have important individual and public health benefits.

Keywords: HIV; antifolate resistance; cotrimoxazole; infant; malaria.

Publication types

  • Observational Study
  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antimalarials / administration & dosage
  • Antimalarials / pharmacology
  • Antimalarials / therapeutic use*
  • Asymptomatic Infections
  • Drug Resistance
  • Female
  • HIV Infections
  • Humans
  • Infant
  • Malaria / drug therapy*
  • Malaria / epidemiology*
  • Malaria / parasitology
  • Malawi / epidemiology
  • Male
  • Parasitemia / drug therapy
  • Parasitemia / epidemiology
  • Parasitemia / parasitology
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / genetics
  • Random Allocation
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage
  • Trimethoprim, Sulfamethoxazole Drug Combination / pharmacology
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*


  • Antimalarials
  • Trimethoprim, Sulfamethoxazole Drug Combination