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Perinatal antiretroviral treatment and hematopoiesis in HIV-uninfected infants

Le Chenadec, Jérômea; Mayaux, Marie-Jeannea; Guihenneuc-Jouyaux, Chantalb; Blanche, Stéphanec; for the Enquête Périnatale Française Study Group

Clinical Science

Background: The perinatal prophylactic administration of zidovudine is associated with rapidly reversible macrocytic anemia in infants. However, a recent study suggests that there may be more persistent inhibition of hematopoïetic stem cells.

Objective: To study hematopoiesis in uninfected infants, born to HIV-1 seropositive mothers, including those exposed and those not exposed to perinatal zidovudine alone or in combination.

Methods: Longitudinal study, from 0 to 18 months, of hemoglobin, platelets, polynuclear neutrophils, total lymphocytes, and CD4+ and CD8+ lymphocytes in more than 4000 infants of the French Perinatal Study. Modeling of repeated measures and non-linear evolution with age, with models combining natural cubic B-splines and random effects.

Results: The hemoglobin level was transiently reduced 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 not exposed infants (P < 0.0001 for each lineage).There was a negative relationship between the duration of exposure and each hematological variable. Combinations of antiretroviral treatments were associated with larger decreases than monotherapy up to 15 months of age. Similar, but less pronounced, patterns were found for the CD4+ and CD8+ subpopulations of lymphocytes.

Conclusions: Zidovudine administered during the perinatal period may result in a small but significant and durable effect on hematopoïesis up to the age of 18 months.

From the aINSERM U569 (Epidémiologie, Démographie et Sciences Sociales) Hôpital Bicêtre AP-HP, 82 rue du Général Leclerc 94276 Le Kremlin Bicêtre Cedex, bINSERM U170 (Recherches épidémiologiques et statistiques sur l'environnement et la santé) 16 avenue Paul-Vaillant-Couturier 94807 Villejuif, CNRS FRE 2428 Université Paris V and cUnité d'Immunologie Hématologie Pédiatrique Hôpital Necker Enfants Malades AP-HP, 149 Rue de Sèvres, 75743 Paris cedex 15, France. *See Appendix.

Correspondence to Stéphane Blanche, Unité d'Immunologie Hématologie Pédiatrique, Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75743 Paris cedex 15, France. E-mail: blanche@necker.fr

Received: 3 October 2002; revised: 3 April 2003; accepted: 16 April 2003.

© 2003 Lippincott Williams & Wilkins, Inc.