Cotrimoxazole Prophylaxis and Risk of Severe Anemia or Severe Neutropenia in HAART-Exposed, HIV-Uninfected Infants

<div><p>Background</p><p>Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia.</p><p>Methods</p><p>We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana.</p><p>Results</p><p>A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure–risk difference, −0.69% (95% confidence interval [CI] −2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI −1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93).</p><p>Conclusions</p><p>Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1–6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants.</p><p>ClinicalTrials.gov Registration Numbers</p><p>NCT01086878 (<a href="http://clinicaltrials.gov/show/NCT01086878" target="_blank">http://clinicaltrials.gov/show/NCT01086878</a>), NCT00197587 (<a href="http://clinicaltrials.gov/show/NCT00197587" target="_blank">http://clinicaltrials.gov/show/NCT00197587</a>), and NCT00270296 (<a href="http://clinicaltrials.gov/show/NCT00270296" target="_blank">http://clinicaltrials.gov/show/NCT00270296</a>).</p>