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

Abstract

BackgroundProphylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia.MethodsWe 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.ResultsA 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).ConclusionsSevere 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.ClinicalTrials.gov Registration NumbersNCT01086878 (http://clinicaltrials.gov/show/NCT01086878), NCT00197587 (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296 (http://clinicaltrials.gov/show/NCT00270296).

Infant Neutropenia Associated with Breastfeeding During Maternal Antiretroviral Treatment for Prevention of Mother-to-Child Transmission of HIV

“…9 However, a previous study comparing infants in the Mma Bana and MASHI studies who did not receive cotrimoxazole with a cohort that received both cotrimoxazole and ART showed no difference in the risk of severe neutropenia by cotrimoxazole exposure. 13 In our study, none of the cases of infant neutropenia were symptomatic, a finding consistent with other studies. 1,7 The clinical significance of neutropenia is still largely unknown, though a study among HIV-1-exposed European infants reported staphylococcal infections related to neutropenia.…”

Effects of concurrent exposure to antiretrovirals and cotrimoxazole prophylaxis among HIV-exposed, uninfected infants

“…A previous study on the effects of CPT on hematologic outcomes in HEU infants in Botswana showed that severe anemia and neutropenia were rare among HEU infants and there was no association between CPT and either outcome [29]. Our research confirms the low frequency of severe neutropenia in HEU infants, while the difference in frequency of severe anemia may be attributable to the different population studied.…”

Multiple Concurrent Illnesses Associated with Anemia in HIV-Infected and HIV-Exposed Uninfected Children Aged 6–59 Months, Hospitalized in Mozambique

“…Cotrimoxazole may directly impact erythropoiesis, causing a reduction in red cell number, yet simultaneously lead to increased Hb levels because of its beneficial effects at reducing malaria and other infections. [29][30][31] Even still, our study results suggest a cause for concern, as HIV-associated anemia has also been shown to increase the risk of mortality. 13 Concern about the high prevalence of anemia in our cohort is heightened by the fact that many HIV-infected and HIVexposed uninfected children in Mozambique are at increased risk for other processes which affect the production of red blood cells, such as nutritional deficiencies from chronic malnutrition, chronic blood loss from helminth infections, and endemic infections such as malaria and TB.…”