Study looks at use of PrEP during pregnancy and breastfeeding

Women in San Francisco and New York City frequently chose to use Truvada for pre-exposure prophylaxis (PrEP) when it was offered as an additional tool for preventing HIV infection during the pre-conception period, pregnancy and breastfeeding, according to study findings presented at the 21st International AIDS Conference (AIDS 2016) in July in Durban, South Africa and published in the 19 July online edition of the American Journal of Obstetrics and Gynecology.

Transmission of HIV to the negative partner is a concern when serodiscordant heterosexual couples wish to conceive. Some couples opt for assisted reproductive technology such as 'sperm washing' (separating individual sperm from semen) and artificial insemination, but these are expensive and not widely available.

Given the development of highly effective antiretroviral therapy (ART) that maintains viral suppression – and the growing recognition that people on treatment with undetectable viral load do not transmit HIV through sex – treatment-as-prevention may be enough to protect the HIV-negative partner when trying to conceive naturally. But adding PrEP offers an extra measure of protection, for example if the positive partner misses medication doses or experiences viral 'blips' for other reasons. If the woman is HIV-negative, protecting her from infection also protects the baby, as recent infection is associated with high viral load that makes mother-to-child HIV transmission more likely.

Once-daily Truvada (tenofovir/emtricitabine) was approved for HIV prevention based on findings from clinical trials, including the iPrEx study of mostly gay and bisexual men and the Partners PrEP study of serodiscordant heterosexual couples, showing that PrEP reduces the risk of HIV infection by 90% or more if used consistently.

To date there have been no randomised controlled studies of Truvada or tenofovir PrEP for pregnant women or those trying to conceive; these are unlikely in the future for ethical and logistical reasons. In PrEP clinical trials women generally stopped the drugs if they became pregnant, and there are no published reports of PrEP use after seven weeks gestation or during lactation. 


However, tenofovir disoproxil fumarate and emtricitabine have been used by thousands of HIV-positive pregnant women over many years as part of antiretroviral treatment. Observational studies and data from the Antiretroviral Pregnancy Registry do not show increased likelihood of birth defects or adverse pregnancy outcomes. These drugs are regarded as generally safe and well-tolerated for both mothers and foetuses, though there is some evidence that infants born to women who take tenofovir during pregnancy may be smaller and have reduced bone density. The Microbicide Trials Network's ongoing EMBRACE study (MTN-016) hopes to shed further light on the safety of PrEP during pregnancy.

Dominika Seidman of the University of California at San Francisco, Shannon Weber of HIVE (who presented the findings at AIDS 2016) and colleagues aimed to characterise use of Truvada for PrEP and to identify gaps in HIV prevention services for women at risk of HIV before conception and during pregnancy and breastfeeding.

Pregnancy is an important opportunity to assess women for HIV risk. Many women who do not otherwise receive regular medical care do seek care when they become pregnant, and many may remain at ongoing risk for HIV infection after giving birth.

The researchers performed a retrospective chart review of 27 women considered to be at 'substantial risk' for HIV infection who received care at two centres – the University of California at San Francisco and Montefiore Medical Center in the Bronx, New York City – between 2010 and 2015. If eligible they were referred to specialty clinics for women living with or at risk of HIV that started offering PrEP in 2010.

Women were identified by clinicians, health educators and health departments. The median time from identification as being at 'substantial risk' to consultation was 30 days, and two women were lost to follow-up before consultation.

About two-thirds (18 women) were identified when they were already pregnant, at a median of five months gestation; none had received counselling about safer conception to reduce HIV risk. About a third (eight women) were identified pre-conception and one was identified during the postpartum period.

The median age was 27 years; 12 were Latina, five were black, four were white, two were Asian and four were of other races/ethnicities. Just over half had unstable housing, 22% had ongoing intimate partner violence, 22% were active substance users and 44% had a history of mental health issues.

All but one of the women had HIV-positive partners and the remaining woman had a male partner who had sex with men. Among the HIV-positive partners, 19 (73%) were on ART and 11 (42%) had documented viral suppression; of the remainder, ten (39%) had known detectable virus and five (19%) had unknown viral loads.

A majority of women were assessed for post-exposure prophylaxis (PEP), but nearly a third were not asked about their recent HIV exposures. Of those assessed, seven were deemed eligible and four of them were offered PEP, but only two started taking it.

Among the 24 women who were offered daily Truvada PrEP, 16 (67%) chose to use it. Among the rest, two-thirds chose to use condoms, over half relied on their partner's treatment-as-prevention and a fifth relied on abstinence. The likelihood of accepting PrEP was similar before conception and during pregnancy.

The median length of time on PrEP was 30 weeks. Half the women reported some challenges in maintaining good adherence, with a third each citing side-effects, social stressors and difficulty taking daily pills. The researchers did not identify any PrEP-related pregnancy complications. There was only one HIV seroconversion, in a woman not taking PrEP.

Half the women on PrEP chose to breastfeed, as did half of those not taking PrEP. Among the women who were in care at the time of delivery, half did not attend a postpartum follow-up visit, so their long-term outcomes are unknown. 

In their conference poster the researchers described three "missed opportunities":

• A woman came to the emergency department after an assault when she was 27 weeks pregnant. She said her partner was living with HIV and not on ART. However, she was not offered PEP or PrEP and was lost to follow-up.
• A second woman was diagnosed with syphilis at 32 weeks into pregnancy. She had multiple partners (some of whom were HIV-positive), was homeless, engaged in sex work and used methamphetamine. She was treated for syphilis and had multiple prenatal care visits, but was never offered PEP or PrEP and was also lost to follow-up. 

• A third woman was identified as being at high risk for HIV infection, with an HIV-positive partner, but was not referred for PrEP due to pregnancy complications including foetal anomalies. She remained in care and was HIV-negative at the time of delivery; her infant died after birth. She was lost to follow-up for awhile but returned to care at 10 months postpartum and was diagnosed with HIV.

"Women at two United States centres frequently chose to use pre-exposure prophylaxis for HIV prevention when it was offered preconception and during pregnancy and lactation," the study authors concluded.

"Further research and education are needed to close critical gaps in screening for women who are at risk of HIV for pre- and post-exposure prophylaxis eligibility and gaps in care linkage before and during pregnancy and lactation," they added. "Postpartum women are particularly vulnerable to loss-to-follow-up and miss opportunities for safe and effective HIV prevention."