Manchester study finds link between increased premature birth rate and HIV

A review of clinical records from Central Manchester University Hospitals has found more evidence of an increased rate of preterm delivery of babies born to HIV-positive women who are taking HIV treatment (antiretroviral therapy or ART), according to a study presented at the eleventh International Congress on Drug Therapy in HIV Infection in Glasgow this week.

The study found a higher rate of preterm delivery in mothers who started ART in pregnancy. However, it also found that the preterm delivery rate was somewhat lower in women who had large CD4 count rises. The researchers therefore recommend that it may be better for women to start ART well in advance of any planned pregnancy rather than start during pregnancy.

The reason for the higher rate of preterm delivery remains unknown. It does not seem to be due to immune restoration in the mother; other theories, such as changes in liver enzyme activity in women on boosted protease inhibitors (PIs), or increased gastro-intestinal side effects, do not seem to be borne out by the fact that preterm birth was no more likely in women taking protease inhibitors than any other class.

The study found that the prevalence of any early birth (defined as delivery before 37 weeks’ pregnancy) was 10.7% in women on ART (10.6% in women on PI-containing regimens, 10.8% in women on non-PI-based regimens). This compared with 7.5% in the general UK population. Babies delivered between 34 and 37 weeks generally do not have a higher rate of health problems than babies born on term at 39 weeks, though they may suffer from low birth weight.

The rate of delivery of babies born before 34 weeks, who have a higher risk of health problems due to prematurity, was 5.8% (6.5% in women on PIs), compared with 3.6% in the general population.

The study was a retrospective case note review of all HIV positive pregnant women treated at North Manchester University Hospital between 2003 and 2012 who took ART at some point during pregnancy.

Altogether there were 208 pregnancies in 157 women; 91% of them were of black African ethnicity, with ages ranging from 16 to 43. Eighty-four per cent of women had an undetectable viral load at delivery (under 40 copies/ml) and the range of viral loads in the detectable minority was 47 to 9120 copies/ml. Twenty-eight per cent of women were diagnosed with HIV during pregnancy, the others beforehand; two-thirds of women who started ART in pregnancy continued on it after having their baby.

Eighty-two per cent of women were on PIs, primarily boosted lopinavir (Kaletra), and the most common non-PI third agent used was nevirapine. No woman took efavirenz. The most common NRTIs were AZT and 3TC.

Women starting ART in pregnancy were 62% more likely to have preterm delivery than women who had started ART earlier, although this was not statistically significant. There was a trend for preterm delivery to increase with age (6.7% more relative risk per year of age).

A UK study cannot tell whether this increased preterm delivery rate is associated with ART use or with having HIV regardless of ART, as few HIV-positive women go untreated. A recent study from Botswana found a higher rate of preterm delivery on women taking combination ART compared with AZT monotherapy, but also found raised rates in all women with HIV compared to the general population. It is also worth pointing out that 40% of preterm delivery in the general population cannot be traced to any cause. Until risk factors are teased out further, the best advice for women with HIV seems to be to start ART in advance of pregnancy and to ensure intensive monitoring of maternal and baby health during pregnancy.