Premature delivery and mother-to-child HIV transmission: a risk/benefit analysis among women receiving HAART

Claire Townsend and co-workers from the Institute of Child Health performed a risk benefit analysis looking at transmission and prematurity among HIV-positive pregnant women receiving HAART, using Monte Carlo modelling. The analysis was based on singleton births, from 1990 to 2007, women reported to the National Study of HIV in Pregnancy and Childhood in the United Kingdom and Ireland.

The investigators used logistic regression models to estimate the association between HAART and both prematurity and mother-to-child transmission (MTCT), adjusting for relevant covariates. They used Monte Carlo simulation methods to estimate the incremental risks (prematurity <37 and <32 weeks) and benefits (reduction in MTCT) compared to AZT monotherapy. They obtained confidence intervals by taking the 2.5% and 97.5% quantiles of the simulated results.

They found that HAART was associated with a 1.5- and 2-fold increase in premature delivery at <37 weeks, (adjusted odds ratio AOR 1.47, 95% CI 1.07-2.02) and <32 weeks (AOR 2.06, 95% CI 0.9 to 3.88), respectively, after adjusting for injecting drug use, HIV symptoms, and CD4 count.

HAART was associated with a 7-fold (87%) decrease in MTCT (AOR 0.13, 95% CI 0.06 to 0.27, n = 5267), compared with early monotherapy (i.e. before 1998, when it was widely used), adjusting for mode of delivery, sex, and gestational age.

In the model the investigators used a scenario of exclusive monotherapy as baseline, with a prematurity rate of 10.3% (107/1037) (1.4%, 15/1037, <32 weeks) and an MTCT rate of 7.0% (12/172). Using Monte Carlo simulation, the investigators estimated an incremental risk-benefit ratio associated with exclusive HAART of 0.68 (95%CI 0.01 to 2.22) premature infants (0.23 at <32 weeks, 95%CI -0.01 to 0.94) for each infection prevented. In other words, preventing HIV in 10 infants by treating women with HAART would result in approximately 7 additional premature births, including 2 at <32 weeks.

The investigators concluded that although prematurity is associated with significant morbidity, long-term complications generally only occur in very premature infants, although there are serious consequences for all HIV-positive children. Therefore they considered HAART superior to monotherapy in these two scenarios.

They noted however that given the risks, in a selected group of healthier women, AZT monotherapy (and elective caesarean) – as in the BHIVA guidelines – remains a reasonable option. They added that the acceptable risk/benefit ratio is likely to vary between populations, depending on available resources and baseline prematurity rates.

Comment

Although based on data from the UK and Ireland, it would be very interesting to see a similar risk benefit analysis applied to settings where interventions for premature babies are uncommon.