Increased risk of severe infant anemia after exposure to maternal HAART, Botswana

Abstract

Background: Maternal highly-active antiretroviral therapy (HAART) reduces mother-to-child HIV transmission but may increase the risk for infant anemia.

Methods: The incidence of first severe anemia (grade 3 or 4, Division of AIDS 2004 Toxicity Table) was assessed among HIV-uninfected infants in the Mashi and Mma Bana mother-to-child HIV transmission prevention trials in Botswana. Severe anemia rates were compared between 3 groups: infants exposed to maternal HAART in utero and during breastfeeding (BF) and 1 month of postnatal zidovudine (ZDV) (HAART-BF); infants exposed to maternal ZDV in utero, 6 months of postnatal ZDV, and BF (ZDV-BF); and infants exposed to maternal ZDV in utero, 1 month of postnatal ZDV, and formula-feeding (ZDV-FF).

Results: A total of 1719 infants were analyzed-691 HAART-BF, 503 ZDV-BF, and 525 ZDV-FF. Severe anemia was detected in 118 infants (7.4%). By 6 months, 12.5% of HAART-BF infants experienced severe anemia, compared with 5.3% of ZDV-BF (P < 0.001) and 2.5% of ZDV-FF infants (P < 0.001). In adjusted analysis, HAART-BF infants were at greater risk of severe anemia than ZDV-BF or ZDV-FF infants (adjusted odds ratios 2.6 and 5.8, respectively; P < 0.001). Most anemias were asymptomatic and improved with iron/multivitamin supplementation and cessation of ZDV exposure. However, 11 infants (0.6% of all infants) required transfusion for symptomatic anemia. Microcytosis and hypochromia were common among infants with severe anemia.

Conclusions: Exposure to maternal HAART starting in utero was associated with severe infant anemia. Confirmation of this finding and possible strategies to mitigate hematologic toxicity warrant further study.

Trial registration: ClinicalTrials.gov NCT00197587 NCT00270296.

Conflict of interest statement

Potential conflicts of interest: M.D.H. is a paid member of Data and Safety Monitoring Boards for Boehringer Ingelheim, Medicines Development, Pfizer and Tibotec. The remaining authors declare that they do not have commercial or other association that might pose a conflict of interest.

Figures

Figure 1

Pattern of severe anemia and mean hemoglobin from birth to 7 months of age, according to exposure group. Panel A shows the proportion of infants with severe anemia. Panel B shows the mean measured hemoglobin at scheduled visits. Mean hemoglobin at 6-7 months of age is significantly different by exposure category for all pairwise comparisons (student's t-test with Bonferroni adjustment). Connecting lines are added for interpretability, but measurements are only available for time points indicated by dots. Bars indicate 95% confidence intervals.

Figure 2

Standardized mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) at the time of incident severe anemia. Panel A shows distribution of age-standardized MCV measurements by exposure group. Panel B displays a plot age-standardized MCV against age-standardized MCHC for incident anemias in the HAART-BF group. Shaded regions in both panels represent normal values. Age-specific normative data , was used to calculate standardized MCV and MCHC (z-score) for incident cases of anemia.