ESPE2016 Rapid Free Communications Adrenals (8 abstracts)
Adrenal Dysfunction in HIV-Exposed Uninfected Infants Receiving Ritonavir-Boosted Lopinavir, an HIV Protease Inhibitor, for the Prevention of Breastfeeding HIV Transmission. An ANRS 12174 Substudy
Michel Polak a, , Stefan Wudy c, , Nicolas Meda e, , Michaela Hartmann c, , Chipepo Kankasa g, , James Tumwine n, , Kathleen Laborde a, , Justus Hofmeyr i , Roselyne Vallo l, , Nicolas Nagot l, , Thorkild Tylleskär j, , Philippe Van de Perre l, & Stéphane Blanche a,
aHôpital Universitaire Necker Enfants Malades, Paris, France; bUniversité Paris Descartes, Paris, France; cCenter of Child and Adolescent Medicine, Giessen, Germany; dJustus Liebig University, Giessen, Germany; eCenter of International Research for Health, Ouagadougou, Burkina Faso; fUniversity of Ouagadougou, Ouagadougou, Burkina Faso; gUniversity Teaching Hospital, Lusaka, Zambia; hUniversity of Zambia, School of medicine, Lusaka, Zambia; iCecilia Makiwane Hospital, East London Hospital Complex, East London, South Africa; jCenter for International Health, Bergen, Norway; kUniversity of Bergen, Bergen, Norway; lINSERM U1058, Montpellier, France; mUniversité Montpellier, Montpellier, France; nSchool of Medicine, College of Health Sciences, Kampala, Uganda; oMakerere University, Kampala, Uganda
Background: We recently demonstrated that both ritonavir-boosted lopinavir (LPV/r) and lamivudine (3TC, a nucleoside analogue) given to breastfed infants can reduce the risk of post natal HIV transmission (ANRS 12174 trial; Nagot, Lancet 2016). In another setting we previously showed the occurrence of adrenal dysfunction in newborn perinatally exposed to LPV/r leading to acute adrenal insufficiency in premature babies (Simon, JAMA 2011).
Objective and hypotheses: Within the ANRS 12174 trial, the administration, randomly assigned, of LPV/r as a monotherapy prophylaxis up to one year in exposed uninfected infants, as compared to 3TC, offered a unique opportunity to study the potential adrenal impact of LPV/r in infants.
Method: According to protocol and ethical authorizations, frozen serum samples collected at Week 6 (W6) and Week 26 (W26) from infants enrolled in Burkina Faso were blindly analyzed using steroid profiling by GC-MS.
Results: 96 infants (LPV/r: 49, 3TC: 47) samples were analyzed. A marked increase of dehydroepiandrosterone (DHEA) was observed in LPV/r exposed infants as compared to 3TC (median (IQR)): 3.0 (1.6–4.8) vs 1.4 (0.5–3.5) at W6 and 0.4 (0.0–0.8) vs 0.1 (0.0–0.3) ng/ml at W26 respectively, both P<0.001). In infants with high DHEA level at W6 (> 5 ng/ml (n=11)), other adrenal hormones were also significantly increased as compared with 38 with DHEA<5).
Conclusion: In comparison with lamivudine, LPV/r exposure during the first year of life is associated with a significant, early adrenal dysfunction sustained during exposure. This effect may result from the interactions between LPV/r and the immature infant’s adrenal and/or an increased ACTH like effect. Further analyses on samples collected after LPV/r discontinuation are pending. There was no difference in severe adverse events incidence between the two treatment groups in the entire cohort (n=1236), but subtle impact on growth and genital development are actively monitored.
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