Antiretroviral therapy and premature delivery in the United Kingdom and Ireland
Polly Clayden, HIV i-Base
Prematurity has been associated with use of antiretroviral therapy in pregnancy in some studies, but not in others.
A paper, authored by Claire Townsend and co-workers, published in the 11 May 2007 edition of AIDS, explored the association between antiretroviral therapy in pregnancy and premature delivery, birthweight, stillbirth and neonatal mortality, in pregnancies in HIV-positive women delivering between 1990 and 2005 in the UK and Ireland. 
Surveillance of obstetric HIV infection in the UK and Ireland, is performed by the National Study of HIV in Pregnancy and Childhood (NSHPC).
Over the study period 5009 pregnancies were reported with an overall rate of prematurity of 13.3% (667/5009). 494 pregnancies were in untreated women and these were excluded from the analysis.
Of the 4445 pregnancies with antiretroviral exposure, most deliveries were by planned caesarean section and the median gestational age was 38 weeks (IQR, 38-39). Most women received HAART in pregnancy, (3384/4445; 76.1%) and this was more frequently NNRTI than PI containing regimens.
The overall prematurity rate (defined as <37 weeks gestation) was 13.1% (583/4445; 95% CI 12.1-14.2); 51.8% (302/583) were at <35 weeks including 23.3% (136/583) at <32 weeks.
The investigators reported a higher rate of prematurity in women receiving HAART, (14.1%, 476/3384) than in women on mono/dual therapy (10.1%, 107/1061), even after adjusting for ethnicity, maternal age, clinical status and injecting drug use as the route of HIV acquisition, AOR, 1.51 (95% CI, 1.19-1.93; p = 0.001). Delivery at <35 weeks was even more strongly associated with HAART, AOR , 2.34 (95% CI, 1.64-3.37, p 0.001). The effect was the same whether or not HAART included a PI.
In comparison with exposure to mono/dual therapy, exposure to HAART was associated with lower birthweight (p<0.001), and an increased but not significant risk of stillbirth, AOR, 2.27 (95% CI, 0.96-5.41, p=0.063).
The authors suggest that their findings raise important questions about the type of treatment used for pregnant women, and in particular, for those not needing HAART for their own health and they write: Although the beneficial effects of antiretroviral therapy on mother-to-child transmission are indisputable, monitoring antiretroviral therapy in pregnancy remains a priority.
The evidence that suppressive antiretroviral therapy is associated with pre-term delivery (PTD) continues to accumulate. In this UK cohort, spanning 15 years and a variety of therapies, HAART is associated with a 1.5 times increased risk of PTD compared with mono or dual therapy. Recently a 1.8 fold increase in PTD with PI-containing HAART was reported from Miami , and an almost 2 fold risk with HAART from Holland  supporting the original reports from the European Collaborative and Swiss Studies. [4, 5]
Whilst for many, if not the majority of, mothers HAART is required either for maternal health or for the prevention of HIV mother to child transmission, especially when maternal viral load is high, the authors conclusions suggest that the use of HAART in all pregnancies may be inappropriate.
It is important to note that in more than 50% the PTD occurred before 35 weeks and in more than 20% before 32 weeks. With increasingly early deliveries neonatal morbidity and mortality increases and survival becomes linked to the availability of resource intense facilities.
The subgroup of mothers for which less intense antiretroviral therapy is most appropriate is likely to vary according to local circumstances, but defining this group is important.
- Townsend C, Cortina-Borja M Peckham C et al. Antiretroviral therapy and premature delivery in diagnosed HIV-infected women in the United Kingdom and Ireland. AIDS. 21(8):1019-1026, May 11, 2007.
- Cotter AM, Garcia AG, Duthely ML et al. Is Antiretroviral Therapy during Pregnancy Associated with an Increased Risk of Preterm Delivery, Low Birth Weight, or Stillbirth? The Journal of Infectious Diseases 2006;193:1195-201.
- Boer K, Nellen JF, Patel D et al. The AmRo study: pregnancy outcome in HIV-1-infected women under effective highly active antiretroviral therapy and a policy of vaginal delivery. Br J Obstet Gynaecol 2007;114:148-55.
- European Collaborative Study, Swiss Mother and Child HIV Cohort Study. Combination antiretroviral therapy and duration of pregnancy. AIDS 2000;14:2913-30.
- Lorenzi P, Spicher VM, Laubereau B et al. Antiretroviral therapies in pregnancy: maternal, foetal and neonatal effects. AIDS 1998;12:F241-F247.