Background: Infants born to HIV-infected women taking predominantly tenofovir (TDF)-based antiretroviral therapy (ART) (mostly with zidovudine/lamivudine) during the DART Trial in Uganda/Zimbabwe were followed in 2004-2009. Methods: Data on pregnancy outcome, congenital abnormalities and maternal/infant ART were collected during DART; information on infant feeding, clinical status, growth, development, HIV status, adverse events and biochemistry/haematology results were collected in a separate infant study (retrospectively in 2004-2006, then prospectively at 3-monthly intervals). The effect of intrauterine ART exposure and feeding practice on growth and mortality were analysed using random effects and time-dependent Cox models. Results: Of 223 livebirths, 6 infants died aged in utero TDF exposure) there were 7 congenital abnormalities (3%): 3 cases of talipes (2 with TDF exposure) and one each of cardiac abnormality, hydrocephalus (with TDF exposure), skin tag (with TDF exposure) and undescended testes; i.e. 3% of TDF-exposed infants had abnormalities. 182 of the 217 surviving infants (84%) were enrolled in the follow-up study; median age at last visit was 26 months (interquartile range 13-39 months); 69% were aged >12 months at last visit. 152/182 (84%) received prophylaxis at birth (sdNVP 44%, ZDV 18%, sdNVP+ZDV 23%, other 15%); 62, 9 and 111 infants were exposed to TDF for none, 20-89% and 90% or more of gestation, respectively. Only 16 (10%) mothers interrupted ART for >4 days during pregnancy. 73/182 infants were ever breastfed, for a median of 3.6 months (IQR 2.5-10.8). All 171 children tested were HIV negative (latest HIV antibody and DNA PCR negative in 101 aged over 18 months and 70 under months respectively); 3 children were lost to follow-up and 8 died before being tested. In total, 14 children died of a variety of causes at median age 9.4 months (IQR 3-23), giving 6% 12 month mortality; 6 were HIV-uninfected and 8 untested. The adjusted HR for mortality for breastfed versus non-breastfed babies was 0.53 [95% CI 0.17-1.63]. There was no evidence of an effect of in utero TDF on growth after 48 weeks (p=0.31) and there were no bone fractures. Only 4/386 creatinine and 7/310 phosphate measurements were abnormal (all grade 1, in 7 children). Conclusion: No increase in congenital, renal or growth abnormalities was observed with in-utero TDF exposure. Although some children died untested, overall infant mortality was similar to that of the general population and absence of recorded HIV infection is encouraging. Given the trend to higher mortality in non-breastfed infants, mothers taking ART during pregnancy and postnatally should be encouraged to breastfeed.
Chidziva, E.; Zalwango, E.; Russell, E.; Kizito, H.; Nalumenya, R.; Gilks, C.F.; Nathoo, K.; Munderi, P.; Tumukunde, D.; Gibb, D.M. Outcomes in infants born to HIV infected mothers receiving long-term ART in the DART trial 2004-2009. Presented at the 17th Conference on Retroviruses and Opportunistic Infections, San Francisco, California, USA, 16-19 February 2010. (2010)