Effects of Cotrimoxazole Prophylactic Treatment on Adverse Health Outcomes Among HIV-exposed, Uninfected Infants

Abstract

Background The World Health Organization guidelines recommend cotrimoxazole prophylactic treatment (CPT) for all HIV-exposed infants from age 6 weeks to the cessation of breastfeeding and the exclusion of HIV infection. There are limited data about the effects of CPT among this population of infants. We examined the effects of CPT on adverse health outcomes among HIV-exposed infants during the first 36 weeks of life by using data from the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study, a large clinical trial of antiretroviral drugs given to the mother or infant for prevention of HIV transmission during breastfeeding. Methods For the analysis, we assigned a status of CPT-exposed to infants who were participating in the study after the CPT program started. We estimated unadjusted and adjusted hazard ratios (HRs) for the effect of CPT status on time to incident malaria, severe illness or death, anemia, and weight-for-age Z score < −2.0. Participation in the study was limited to focus exclusively on HIV-exposed, uninfected infants. Results The HR for the effect of CPT on incident malaria was 0.35 (95% confidence interval [CI]: 0.21, 0.57) during the first 10 weeks of CPT exposure, and 0.93 (95% CI: 0.67, 1.29) for the remaining 20 weeks. CPT was not associated with the other outcomes examined. Conclusions CPT offered temporary protection against malaria among HIV-exposed, uninfected infants. However, CPT offered no protection against anemia, low weight for age, or the collapsed outcome of severe illness or death.

Antiretroviral Treatment Is Associated With Iron Deficiency in HIV-Infected Malawian Women That Is Mitigated With Supplementation, but Is Not Associated With Infant Iron Deficiency During 24 Weeks of Exclusive Breastfeeding

“…Infants randomized to ARV received daily oral nevirapine (details previously reported 17 . Starting on June 13, 2006, cotrimoxazole prophylaxis (CPT) (240 mg once daily) was provided to all infants >6 weeks old and initiated for all mothers with a CD4<500 cells/uL in pregnancy; 23 in this report 68% and 43% of infants and mothers received CPT, respectively. In March 2008, the data safety monitoring board at the National Institute of Allergy and Infectious Diseases reviewed data from the enrolled 1857 mother-infant pairs and observed that HIV transmission through breast milk was higher in the no-drug study arms.…”

Cotrimoxazole prophylactic treatment prevents malaria in children in sub‐Saharan Africa: systematic review and meta‐analysis

“…In total 1692 HIV‐exposed, 2800 HIV‐uninfected and 1486 HIV‐infected children aged between 6 weeks (Dow et al . ) and 15 years (Thera et al . ) were included in the meta‐analyses.…”

“…The only exception was the study by Dow et al . (), which compared the incidence of malaria between HIV‐exposed children before and after 2006, the year CPT guidelines were introduced in Malawi. All studies adjusted for potential confounders at the analysis stage; however, the variables included in the multivariable models differed across studies (Appendix 3).…”

HIV-exposed infants

“…However, other than temporary protection from malaria, CPT offered no protection against anemia, malnutrition or severe illness and death for HIV negative children. [16,17] Given limited data that CPT may increase risk of diarrheal illness in HIV uninfected infants there is a need to define the optimal duration of cotrimoxazole prophylaxis and possibly reexamine current guidelines. [18]…”