BOSTON — HIV-exposed uninfected children did not see a survival benefit when assigned to cotrimoxazole, according to results presented Tuesday at CROI 2016.
The Data and Safety Monitoring Board stopped the study early after determining that HIV-exposed uninfected children were unlikely to benefit from the treatment.
Previous studies have shown that cotrimoxazole reduces mortality among children with HIV and researchers had hoped this study would find a similar effect among HIV-exposed uninfected newborns in Botswana.
There were 30 deaths in the treatment arm compared with 34 in the placebo arm. Estimated mortality at age 18 months was 2.4% vs. 2.6% for a difference of 0.2% (95% CI, -1.0% to 1.5%).
“The results were fairly clear that there was no benefit to cotrimoxazole.” said Roger L. Shaprio, MD, MPH, an associate professor of medicine at Harvard Medical School and Harvard School of Public Health.
About 20% of children in the study breastfed, and those children were protected either by maternal antiretroviral therapy or direct infant prophylaxis with nevirapine. Only two children in that population were infected during breastfeeding, for a late transmission rate of 0.35%.
The WHO recommends that all infants born to women with HIV receive cotrimoxazole until the child is proven to be uninfected and the period of HIV transmission risk has ended as a safeguard against severe infections and death if the child becomes infected with HIV. These findings suggest that such prophylaxis may not be necessary, according to the study researchers.
“In non-malarial settings with low overall mortality, routine cotrimoxazole prophylaxis may not be required among HIV-exposed uninfected children who have a low ongoing MTCT risk,” Dr. Shapiro said.
From May 2011 to April 2015, children aged from 14 days to 34 days through 15 months were randomly assigned to cotrimoxazole (n=1,432) or placebo (n=1,434). Children were followed every 1 to 3 months through 18 months; infants diagnosed with HIV after randomization transitioned to open-label cotrimoxazole.
Results were similar in the treatment and placebo arms hospitalization (10.8% vs. 12.4%, P=0.24), grade 3/4 diagnosis (16.1% vs. 17.8%, P=0.36), or grade 3/4 anemia (8.0% vs. 8.2%, P=0.84). Researchers also noted that infants in the treatment arm were more likely to experience grade 3/4 neutropenia (7.9% vs. 5.8%, P=0.05).
1. Shaprio RL. 37. Similar Mortality With Cotrimoxazole vs Placebo in HIV-Exposed Uninfected Children. Presented at: CROI 2016. Feb. 22-25, 2016. Boston.