Pregnancy outcomes in the DART trial
Polly Clayden, HIV i-Base
The DART trial is a 6 year randomised trial of ART monitoring strategies in adults with symptomatic HIV and CD4 <200 cells/mm3 initiating ART in Kampala and Entebbe (Uganda) and Harare (Zimbabwe). Of the 3316 DART participants, 1867 are women of child-bearing age <45 years.
A poster authored by Letitia Namale from Uganda and coworkers presented findings from an evaluation of pregnancy and pregnancy outcomes among women participating in the DART trial at a median of 2.8-years of follow-up.
221 pregnancies were reported in 198 (10.6%) women <45 years at enrolment (4.6/100 person-years, 95% CI 4.0 to 5.2); 19 had 2, and 2 women had 3 pregnancies. The median (IQR) baseline CD4 was 115 (49 to 158) cells/mm3 in women who became pregnant vs 87 (31 to 140) cells/mm3 in those who did not become pregnant (p<0.001). 18% vs 25% were WHO stage 4 at baseline (p= 0.07).
The investigators reported that the pregnancy rate increased with time on ART (3.7, 4.3, and 5.9/100 person-years 0 to 6, 7 to 12, >12 months from ART initiation respectively). Overall pregnancy rates increased during the first 18 months of follow up but are currently stabilising. In younger women the rise was marked over the first year followed by a decline. They suggested that this could be explained by unexpected return of fertility with improved health on ART, followed by greater use of contraception with counseling.
The proportions of women becoming pregnant in Entebbe, Kampala, and Harare were 14.4%, 8.4%, and 10%, respectively (29%, 15%, and 20% women were aged 18 to 30 years). The investigators noted that, pregnancy rates vary by centre with younger women in rural Entebbe having almost double the rates seen in urban Kampala, 30 miles away.
All women took ART in pregnancy and all but one continued through delivery. 27 (12%) pregnancies are ongoing and 9 (4%) with gestation >40 weeks have outcome currently unknown. Among 164 with known outcome and pregnancy started >40 weeks ago, ART regimens at start of pregnancy were combivir with tenofovir (TDF; 70%), nevirapine (NVP; 15%), or abacavir (ABC; 4%), stavudine-containing regimens (d4T; 3%), other (2%). Overall 78% women took TDF at some time during their pregnancy.
87% of the women stayed on the same regimen throughout their pregnancy, or had breaks of <4 weeks. 4% switched one or more drugs and 8% had more than 4 weeks break during pregnancy.
With respect to outcome of pregnancy, there were 91 (55%) live births, 11 (7%) stillbirths, and 62 (38%) terminations. 31 (19%) reported as induced and 31 (19%) as spontaneous. 47 (76%) of the terminations were reported as being less than 15 weeks gestation, although investigators also noted that gestational age was generally not precisely known, particularly for pregnancies first reported when already aborted or miscarried.
The investigators also explained that they were unable to always clearly distinguish between induced abortion and spontaneous abortion/miscarriage in this setting. They explained that medical abortion is not legal in Uganda; in Zimbabwe, an HIV positive woman may have an abortion on medical recommendation. Women terminating unwanted pregnancies themselves may be reluctant to disclose this, and these may be recorded as spontaneous abortion/miscarriage. Pregnancy intentions are not currently recorded in DART either prospectively or retrospectively although there are plans to do further work on this.
74 (73%) of the 102 births were delivered vaginally, 18 (18%) were delivered by cesarean (9 emergency, 9 elective) and 10 (10%) were of unknown mode of delivery. 18 (18%) had gestation <37 weeks (10 live births [6 <33 weeks], 8 stillbirths [8 <33 weeks]), and 3 (3%) had congenital abnormalities (2 club foot, 1 hydrocephalus [baby died]). Four women died (1 following post-partum hemorrhage, 1 puerperal psychosis, 1 septic abortion, 1 malaria).
70 of 91 infants, (77%) received ART (single-dose NVP 42%, 7-15 days AZT 13%, single-dose NVP+ZDV 20%, other 4%).
10 (11%) infants were premature (24-36 weeks). There have been 5 neonatal deaths, 3 within 24 hours (2 <37 weeks).
Despite receiving HAART only 22 (26%) of 86 infants known to be alive at 2 weeks were breast-fed. No infant has yet been diagnosed as HIV infected.
Follow up of infants born to DART mothers has received ethical approval and is about to start.
This is the largest study to date of women receiving tenofovir in pregnancy (and of triple RTI combinations).
Although the precise rate is uncertain because of issues around legal abortion, the rate of spontatneous miscarriage is relatively high but similar rates have been reported elsewhere.
It is interesting to note that at two weeks only 26% of women reported breatfeeding their infants despite receiving HAART.
Namale L, Zalwngo E, Chidziva E et al. Pregnancy and Pregnancy Outcome among Women in the DART Trial. Poster Abstract 746.