Pregnancy rates and outcomes among women in the DART trial
Polly Clayden, HIV i-Base
Pregnancy rates and outcomes and outcomes among women participating in DART were shown in a poster authored by Paula Munderi and coworkers on behalf of the DART trial team. 
The investigators had previously shown findings from an evaluation of pregnancy at a median of 2.8-years of follow-up, which we reported previously in HTB. 
This further analysis was at a median of 4.6 years follow-up from January 2003 to June 2008, and included information on maternal/infant outcomes and infant feeding. Longer-term infant follow-up and documentation of infant outcomes are ongoing in a separate sub-study.
Of the 2156 women enrolled in DART, 1876 (87%) were of childbearing age (<45 years). No women were pregnant at enrollment and pregnancy tests were performed six-monthly. Women in DART were given contraceptive advice, including free condoms, counselled if they wished to conceive, and encouraged to disclose any pregnancy.
If they became pregnant on the trial they continued HAART in their study randomisation, received extra diagnostics as required for pregnancy within the trial, and were referred for routine antenatal care.
Data on infant follow up to 2 weeks of age were analysed for congenital abnormalities, early infant survival, and HIV status if tested.
The investigators reported that 378 pregnancies occurred in 299 women. The majority had one pregnancy (n=235) but 50, 13 and 1 women/woman had 2, 3 and 4 pregnancies respectively.
Multiple pregnancies occurred in 16% women <45 years and 33% women <30 years and this rate was similar across sites.
The overall pregnancy rate in women <45 years was 4.83/100 woman years (95% CI 4.36-5.34). Incidence pregnancy rates peaked at 2-3 years across all age groups and then declined. It was highest in the 18-29 years age group.
The median CD4 count was greater among women who were ever pregnant vs never pregnant 106 (IQR 32-142) vs 87 (IQR 31-141) cells/mm3 respectively, p=0.01.
The majority of mothers (60%) received TDF+AZT+3TC regimens. Of the remaining, 17% received NVP+AZT+3TC; 7% d4T-containing HAART; 6% second-line with LPV/r; 5% ABC+AZT+3TC; 3% were off HAART and 2% received other first line HAART.
Four mothers died, 2 during pregnancy (I due to malaria, 1 due to septic abortion) and 2 peripartum (1 post partum haemorrhage and 1 puerperal psychosis).
There were 206 live births and 26 stillbirths. Any congenital abnormalities were reported in 7 (3%) infants. These were club-foot (3; 2 tenofovir, 1 nevirapine); hydrocephalus (1 tenofovir, died); cardiac anomaly (1 nevirapine); undescended testes (1 nevirapine) and skin tag on neck (1 tenofovir).
Prematurity <37 weeks occurred in 9% live births (16% live and still births). Low birth weight <2.5kg occurred in 17% of live births (13% >=37 weeks). The mean weight in infants >37 weeks was 3.0kg (SD +0.54).
At two weeks post partum, the investigators reported 9 neonatal deaths, of which 6 occurred within 24 hours; 5 infants were HIV-DNA PCR negative and 4 were not tested. Causes of death were: foetal distress (2), prematurity (1), intestinal obstruction (1), haemorrhagic disease (1) and 4 were from unknown causes.
Only a small number of children (n=15, 7%) were tested by the DART assessment visit at 2 weeks and none were HIV-infected.
The infant follow up sub-study has enrolled 174/206 infants. Of these 152 are known to be still alive. Of the 137/174 (74%) infants with results available, none are HIV-infected.
At two weeks only a minority of women (30%), across all study sites, chose to breastfeed.
The investigators concluded that in this group of women, pregnancy rates increased after the first year and declined from the fourth year on HAART. Rates were higher among younger women with less severe HIV disease.
Rates of foetal loss were high and are consistent over time. They suggest that this may reflect improved reporting within a clinical trial but note that increased foetal loss has been reported in other studies.
The low rates of congenital abnormalities are encouraging and similar to those shown elsewhere: 3.0/100 95%CI 2.4-3.7) among HIV-positive women with first trimester HAART exposure in the Antiretroviral Pregnancy Register (APR) and 2.7/100 live births in the CDC birth defects register.
At first sight the preterm delivery rate is encouragingly low, much lower than in most other studies (eg 19% in DREAM see above, 17% in Europe, 18% in North America). Contributing factors may include conception on therapy, negating the effect of HIV infection on preterm delivery, and the regimen prescribed. Conversely the stillbirth rate is high and highly associated with preterm delivery. More data on the gestational age are needed to interpret these findings.
The low rates of congenital abnormalities are also encouraging and this large dataset from women receiving TDF in pregnancy is very useful. These data have been submitted to the Antiretroviral Pregnancy Registry.