Background:  Infants born to women taking predominantly tenofovir (TDF) -based ART during the DART Trial in Uganda and Zimbabwe were followed from 2004 to 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/hematology results were collected in a separate infant study (retrospectively, 2004 to 2006, then prospectively 3 monthly). Effect of intrauterine ART exposure and feeding practice on growth and mortality were analyzed using random effects and time-dependent Cox models.

Results:  Of 223 live births, 6 infants died <2 weeks from perinatal causes (fetal distress, 3; prematurity, 2; hemorrhagic disease, 1). There were 7 (3%) congenital abnormalities (talipes [2*,1], cardiac, hydrocephalus*, skin tag*, undescended testes); 4 (3%) of 129 with TDF exposure (* in above). Of 217 surviving infants, 182 (84%) were enrolled in the follow-up study; median age at last visit was 26 months (IQR 13 to 39); 69% were >12 months. Of 182 infants, 152 (84%) received prophylaxis (single-dose nevirapine [sdNVP] 44%, zidovudine [ZDV] 18%, sdNVP+ZDV 23%, other 15%):  62 / 9 / 111 infants had no / 20 to 89% / ≥90% in utero TDF exposure during gestation; only 16 (10%) mothers interrupted ART for >4 days during pregnancy. Of 182 infants, 73 were ever breastfed for median 3.6 months (IQR 2.5 to 10.8). All 171 children tested were HIV^– (latest HIV antibody and DNA polymerase chain reaction negative in 101 ≥18 months and 70 ≤18 months, respectively); 3 children were lost to follow-up and 8 died before being tested. In total, 14 children died at median age 9.4 months (IQR 3 to 23), giving 6% 12-month mortality:  6 were HIV-uninfected; 8 untested died of respiratory infection (3), sepsis (2), burns, measles, unknown. The adjusted HR for mortality for breastfed vs non-breastfed babies was 0.53 (95%CI 0.17 to 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 of 386 creatinine and 7 of 310 phosphate measurements were abnormal (all grade 1, in 7 children).

Conclusions:  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.