Pre-exposure Prophylaxis Does Not Affect Pregnancy Outcomes

The first study to assess the safety of pre-exposure prophylaxis (PrEP) in women who are becoming pregnant shows that antiretroviral treatment does not affect a woman's ability to become pregnant and does not appear to adversely affect fetal outcomes.

“Differences in pregnancy incidence, birth outcomes, and infant growth were not statistically different for women receiving PrEP with tenofovir disoproxil fumarate (TDF) alone or combination emtricitabine/tenofovir disoproxil fumarate (FTC+TDF) compared with placebo at conception,” state the researchers.

They report follow-up data on pregnancy outcomes from the Partners PrEP study for the prevention of HIV infection serodiscordant heterosexual couples in Africa. The previous report from this study demonstrated the efficacy of TDF with or without FTC in reducing HIV incidence, with key safety outcomes no different than placebo. The trial was unblinded in 2011, and patients who had received placebo were re-randomized to FTC + TDF or TDF alone and were followed for pregnancy outcomes for 12 or more months.

The efficacy results from the initial stages of the Partner PrEP Study were published in the New England Journal of Medicine.¹

In the new analysis, patients received either daily oral TDF (598 patients), combination FTC+TDF (566 patients), or placebo (621 patients) when PrEP demonstrated efficacy for HIV prevention. Thereafter, the patients continued receiving active PrEP without placebo. Pregnancy testing occurred monthly and study medication was discontinued when pregnancy was detected.

Among 1,785 couples in which the female partner was not infected with HIV, 431 pregnancies were recorded. There was no significant difference in pregnancy incidence among women in the FTC + TDF, TDT alone, or placebo groups, and there was no significant difference in the rates of pregnancy loss, preterm birth, or congenital abnormalities.

The frequency of pregnancy loss (52 of 143 pregnancies) was 37.5% for FTC+TDF and 36.7% for TDF alone, they report.

On average, women in the study who were receiving PrEP were pregnant for only about 35 days. The researchers note that given that PrEP was discontinued when pregnancy was detected and that confidence intervals for the birth outcomes were wide, definitive statements about the safety of PrEP in the periconception period cannot be made.

In addition, there was a suggestion of a signal of potential harm because pregnancy loss did appear to be higher with the combination PrEP regimen. Although women in this study were not exposed to the nucleosides for longer than 6 weeks into pregnancy, in the real world, exposure to these drugs might be longer.

“The conservative clinician's choice in this difficult decision of a possible harm signal for pregnancy outcomes will be to target antiretrovirals to the HIV-infected partner, especially men in a heterosexual relationship, and to reserve PrEP for women who may have other unprotected exposures outside the primary relationship,” the editorialists state.

In addition, “clinicians also have a responsibility to ensure patients are equipped to make informed decisions about how they manage risk and to choose the combination of prevention methods that suit their individual circumstances, values, and preferences,” they state.

The researchers reported their results in the July 23/30, 2014 issue of JAMA.²

References:

1. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med.2012;367:399-410.

2. Mugo NR, Hong T, Celum C, et al. Pregnancy incidence and outcomes among women receiving preexposure prophylaxis for HIV prevention: a randomized clinical trial.JAMA.2014;312:362-371.