First, the differences in hemoglobin concentration and neutrophil count, although statistically significant, were minimal. Second, the differences in platelet, total lymphocyte, CD4+, and CD8+ cell counts between ARV‐unexposed and ‐exposed infants were significant at most visits throughout the period of study.
Number of infants with 1 event of clinically relevant hematologic abnormalities, by ARV exposure status.We evaluated the incidence of clinically significant laboratory abnormalities among the various ARV exposure groups. Clinically significant abnormalities were defined as grade 3 toxicities in the Division of AIDS pediatric toxicity tables. These thresholds included hemoglobin concentration <7 g/dL, platelet count <50,000/mm3, neutrophil count <400 cells/mm3, and CD4+ cell count <750 cells/mm3 in infants age <12 months or <500 cells/mm3 in infants age 12–24 months. Less than 3% of children had 1 hematologic or lymphocytic value in this abnormal range, and the proportion of infants with 1 occurrence of these values did not differ significantly among the various ARV exposure groups. These data from WITS, a large cohort study in the United States, demonstrate that several hematologic parameters are lower in HIV‐exposed, uninfected infants with in utero and/or neonatal exposure to ARV drugs, although these differences are small and appear to be clinically insignificant. The hematologic effects of exposure to ARV drugs observed during the first 2 months of life could be secondary to the ongoing exposure to ARV drugs given to the infant during the first 6 weeks of life to prevent the transmission of HIV. However, although the difference in hemoglobin concentration resolved and that in neutrophil count became insignificant after age 2 months, significant differences persisted for platelet, lymphocyte, CD4+, and CD8+ cell counts through age 24 months. Although exposure to ARV drugs in WITS was not randomized and there were changes over time in certain aspects of the study population and in the use of ARV drugs, the findings persisted even after we controlled for a number of parameters that have been shown to be associated with hematologic variables in other studies, such as maternal race/ethnicity, drug use, maternal CD4+ cell count at delivery, and infant gestational age, birth weight, sex, and age. Despite some differences in methodology and considerable differences in race/ethnicity, similar findings were reported from the French Perinatal Cohort Study Group and the European Collaborative Study.
In the French Perinatal Cohort Study, HIV‐uninfected infants with perinatal exposure to ARV drugs had significantly lower hemoglobin concentrations and platelet, neutrophil, total lymphocyte, CD4+, and CD8+ cell counts than HIV‐exposed infants without perinatal exposure to ARV drugs. Although differences in hemoglobin concentrations resolved by age 2 months, the differences in the other hematologic parameters persisted through age 18 months. Those researchers reported that exposure to combination ARV drugs was associated with larger decreases than exposure to ARV monotherapy up to age 15 months. In addition, there was a negative relationship between the duration of treatment and neutrophil and lymphocyte counts, and a lower maternal CD4+ cell count at delivery was associated with lower infant lymphocyte and CD4+ cell counts.