Cotrimoxazole prophylaxis and risk of severe anemia or severe neutropenia in HAART-exposed, HIV-uninfected infants

Scott Dryden-Peterson, Oluwemimo Jayeoba, Michael D Hughes, Haruna Jibril, Kenneth McIntosh, Taolo A Modise, Aida Asmelash, Kathleen M Powis, Max Essex, Roger L Shapiro, Shahin Lockman, Scott Dryden-Peterson, Oluwemimo Jayeoba, Michael D Hughes, Haruna Jibril, Kenneth McIntosh, Taolo A Modise, Aida Asmelash, Kathleen M Powis, Max Essex, Roger L Shapiro, Shahin Lockman

Abstract

Background: Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia.

Methods: 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.

Results: 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).

Conclusions: 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. CLINICALTRIAL.SGOV REGISTRATION NUMBERS: NCT01086878 (https://ichgcp.net/clinical-trials-registry/NCT01086878), NCT00197587 (https://ichgcp.net/clinical-trials-registry/NCT00197587), and NCT00270296 (https://ichgcp.net/clinical-trials-registry/NCT00270296).

Conflict of interest statement

Competing Interests: Dr. Hughes was previously a paid member of the Data and Safety Monitoring Boards for Boehringer Ingelheim, Medicines Development, Pfizer and Tibotec. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Schematic of infant exposures in…
Figure 1. Schematic of infant exposures in study cohorts.
ZDV, zidovudine; supp., supplementation; CTX, cotrimoxazole; HAART, highly-active antiretroviral therapy; mo., month. aHAART became available through a national program in October 2002, subsequently women in Mashi trial with CD4≤200 cells/ µL were offered HAART. bInfants in the Mma Bana trial received 1 month of ZDV and breastfed infants in the Mashi trial received 6 months of ZDV. cNineteen mothers (9.1%) in CTX cohort received non-ZDV-containing HAART.
Figure 2. Enrollment and follow-up of study…
Figure 2. Enrollment and follow-up of study infants.
HIV-uninfected infants in the Mashi and Mma Bana trials did not receive cotrimoxazole prophylaxis and serve as a comparison group to the new cohort (CTX) that received cotrimoxazole prophylaxis. CTX, cotrimoxazole; 1 mo., one month; FF, formula-fed; BF, breastfed.

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