Perinatal antiretroviral treatment and haematopoiesis in HIV-uninfected infants

A report from the French Perinatal Study published in the September issue of AIDS found that perinatal exposure to zidovudine might result in a small but significant and durable effect on haematopoiesis up to the age of 18 months.

The French Perinatal Study, established in 1986, prospectively follows infected and uninfected infants born to HIV-positive mothers.

In a longitudinal study, the investigators analysed haematological variables in 4,249 infants from zero to 18 months including haemoglobin, platelets, polynuclear neutrophils, total lymphocytes, and CD4+ and CD8+ lymphocytes. To perform the analysis they used non-parametric smoothing techniques. Modeling of repeated measures and non-linear evolution with age, with models combining natural cubic B-splines and random effects.

The investigators reported a transient reduction in haemoglobin levels in newborns exposed to zidovudine. Multivariate analysis taking into account age, prematurity, geographical origin, maternal drug use and maternal CD4 cell count, indicated that levels of the three other lineages were slightly lower until age 18 months in exposed than in not exposed infants (p < 0.0001 for each lineage). They report a negative relationship between the duration of exposure and each haematological variable.

Additionally, combinations of antiretrovirals were associated with larger decreases than zidovudine monotherapy up to 15 months of age. Similar, but less pronounced, patterns were found for the CD4+ and CD8+ subpopulations of lymphocytes.

The investigators concluded: “Zidovudine administered during the perinatal period may result in a small but significant and durable effect on haematopoïesis up to the age of 18 months.” They also noted that the clinical consequence of these findings are probably minor or non-existent and: “A more detailed analysis of CD4/CD lymphocyte sub-populations (ie naïve/memory phenotype and function) could be of value as would long term evaluation.”

Le Chenadec J, Mayaux MJ, Guihenneuc-Jouyaux C et al. Perinatal antiretroviral treatment and haematopoiesis in HIV-uninfected infants AIDS 2003, 17(14):2053-2061