Protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children in rural Uganda: a randomised clinical trial

Taylor G Sandison, Jaco Homsy, Emmanuel Arinaitwe, Humphrey Wanzira, Abel Kakuru, Victor Bigira, Julius Kalamya, Neil Vora, James Kublin, Moses R Kamya, Grant Dorsey, Jordan W Tappero, Taylor G Sandison, Jaco Homsy, Emmanuel Arinaitwe, Humphrey Wanzira, Abel Kakuru, Victor Bigira, Julius Kalamya, Neil Vora, James Kublin, Moses R Kamya, Grant Dorsey, Jordan W Tappero

Abstract

Objective: To evaluate the protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children (uninfected children born to HIV infected mothers) in Africa.

Design: Non-blinded randomised control trial

Setting: Tororo district, rural Uganda, an area of high malaria transmission intensity

Participants: 203 breastfeeding HIV exposed infants enrolled between 6 weeks and 9 months of age

Intervention: Co-trimoxazole prophylaxis from enrollment until cessation of breast feeding and confirmation of negative HIV status. All children who remained HIV uninfected (n = 185) were then randomised to stop co-trimoxazole prophylaxis immediately or continue co-trimoxazole until 2 years old.

Main outcome measure: Incidence of malaria, calculated as the number of antimalarial treatments per person year.

Results: The incidence of malaria and prevalence of genotypic mutations associated with antifolate resistance were high throughout the study. Among the 98 infants randomised to continue co-trimoxazole, 299 malaria cases occurred in 92.28 person years (incidence 3.24 cases/person year). Among the 87 infants randomised to stop co-trimoxazole, 400 malaria cases occurred in 71.81 person years (5.57 cases/person year). Co-trimoxazole prophylaxis yielded a 39% reduction in malaria incidence, after adjustment for age at randomisation (incidence rate ratio 0.61 (95% CI 0.46 to 0.81), P = 0.001). There were no significant differences in the incidence of complicated malaria, diarrhoea, pneumonia, hospitalisations, or deaths between the two treatment arms.

Conclusions: Co-trimoxazole prophylaxis was moderately protective against malaria in HIV exposed infants when continued beyond the period of HIV exposure despite the high prevalence of Plasmodium genotypes associated with antifolate resistance. Trial registration Clinical Trials NCT00527800.

Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work, no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4788034/bin/sant811646.f1_default.jpg
Fig 1 Participant flow through trial
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4788034/bin/sant811646.f2_default.jpg
Fig 2 Time to first malaria episode among 185 HIV uninfected children randomised to continued co-trimoxazole prophylaxis versus no prophylaxis (P=0.003 for difference)
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4788034/bin/sant811646.f3_default.jpg
Fig 3 Protective efficacy of co-trimoxazole prophylaxis against malaria, diarrhoea, and respiratory tract infections among 185 HIV uninfected children randomised to continued co-trimoxazole prophylaxis versus no prophylaxis. (IRR=incidence rate ratio (95% CI) adjusted for age at randomisation)
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4788034/bin/sant811646.f4_default.jpg
Fig 4 Protective efficacy of co-trimoxazole prophylaxis against malaria among 185 HIV uninfected children randomised to prophylaxis versus no prophylaxis by time after randomisation and participant age (using locally weighted scatterplot smoothing (LOWESS))

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Source: PubMed

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