Pregnancy, family planning, and HIV acquisition in HPTN 039
Polly Clayden, HIV i-Base
Pregnancy has been reported to be a period during which women may be at an increased risk of HIV acquisition.
It is usual in HIV prevention trials to remove women from study drug during pregnancy.
A poster from the HPTN 039 study group showed findings from an analysis of the effect of pregnancy on time off study drug and risk of HIV acquisition. This was a randomised double-blind placebo-controlled trial that studied the efficacy of herpes simplex virus-2 (HSV-2) suppression with acyclovir, to prevent HIV acquisition.
There were 1358 HIV-negative, HSV-2-positive women from Zimbabwe, Zambia, and South Africa enrolled in HPTN 039. Women who were pregnant at either screening or enrollment were ineligible, and study drug was discontinued if women became pregnant while in the trial. Contraception services were provided at trial sites.
The investigators used a Cox proportional hazard model stratified by trial site, and adjusted for baseline predictors and time-varying sexual behavior covariates to estimate risk of acquiring HIV.
They reported 226 pregnancies during 18 months of follow up. These occurred at a median time of 7.9 months from enrollment. The incidence of pregnancy was 13.2/100 person years, which accounted for 4% of missed time on study drug among women in the trial (of note only 47.8% of pregnancies were full term).
In multivariate analyses, younger age, contraceptive use and unmarried status were associated with pregnancy. (See Table 1).
Table 1. Risk factors for pregnancy
|Risk factor||HR||95% CI||p|
|Age >34 vs<21 years||0.22||0.13-0.38||p=<0.0001|
|Oral contraception vs none||0.68||0.47-0.98||p=0.05|
|Injectable contraception vs none||0.24||0.14-0.4||p<0.001|
Condom use was not effective as contraception in this study, condom use vs none [HR 1.1;2 95% CI 0.71-1.75, p=0.63]. There was no evidence that women were of increased risk of HIV acquisition during pregnancy through to 6 weeks post partum [HR 0.64, 95%CI 0.23-1.78, p=0.4].
Risk factors for HIV acquisition were: younger age (>34 vs<21 years HR 0.28 (0.13-0.61), p<0.001); new partners in last 6 months (yes vs no HR 3.98 (95% CI 1.6-9.8), p=0.003); lack of condom use (condom use vs none, HR 0.27(95%CI 0.08-0.96), p=0.04) and bacterial vaginosis (HR 2.05 (1.2-3.6), p=0.01).
The investigators wrote: For biomedical HIV prevention trials, on-site provision of contraceptive methods and family planning education can reduce pregnancies and time off study drug.
Previous studies have suggested that pregnancy may increase the risk of HIV transmission and that this is due to the biological state of pregnancy rather than any behavioral factors. This study shows no increased risk with pregnancy. These conflicting findings need to be explored.
It is worth noting that, while not effective as contraception, condom use was associated with a significant reduction in HIV transmission risk. However, it may be very difficult to separate out the effects of pregnancy and sexual behaviour (as I guess that women will reduce their sexual activity when they are pregnant).
Reid et al. Pregnancy, family planning, and HIV acquisition in HIV Prevention Trials Network 039: relevance for HIV prevention trials among Sub-Saharan African women. 16th CROI, February 2009, Montreal, Canada. Poster abstract 985.