HIV Prevention among Pregnant and Breastfeeding People

Pregnant and Breastfeeding People are at Higher Risk of HIV

Global efforts to expand options for HIV prevention are robust, but they must be paired with efforts to understand how well they work and will be accepted among populations of pregnant and breastfeeding people (PBFP). A number of diverse products are in various phases of development, including new oral PrEP drugs, the Dapivirine Vaginal Ring (DVR), the dual prevention pill (DPP), cabotegravir long-acting (CAB-LA), and others in earlier phases of clinical research. The potential of these products among pregnant and breastfeeding people demands further investigation, and prevention programs must be designed with guidance and leadership from these communities so these life-saving products reach those who need them most.

A pregnant person is 2-3 times more likely to acquire HIV during pregnancy and 4 times more likely to acquire HIV post-partum than otherwise. In other words, PBFP are generally at higher risk of acquiring HIV compared to non-pregnant or lactating people. Studies show that about 1/3 of all new HIV infections in people happen during late pregnancy or breastfeeding. And when a person is at higher risk for HIV, so is their baby.

Evidence of High Rates of HIV Incidence During Pregnancy & Breastfeeding

A large-scale study recently analyzed pooled data on HIV incidence among pregnant African women. The results: a rate of 4.7 for every 100 person-years and 2.9 during the postpartum period. These rates are among the highest of any population, exceeding HIV incidence among female sex workers and serodiscordant couples.

Researchers looking at serodiscordant couples have also found the probability that an HIV negative woman will become positive (when her partner has HIV and is not on ART) goes up significantly when she’s pregnant.

Biological factors contribute to this heightened risk. For example, high levels of estrogen and progesterone that accompany pregnancy can induce a cascade of changes within the female genital tract, including increased inflammation, decreased integrity of the vaginal epithelium, and changes in the microbiota present in the vagina. All these factors have been associated with increased risk of HIV acquisition

High Risk in PBFP Translates to High Rates of MTCT of HIV

Because a large proportion of pregnant people living with HIV, particularly in sub-Saharan Africa, are neither diagnosed nor offered ART, UNAIDS documents that just over 1,200,000 women globally were living with HIV infection while they were pregnant or breastfeeding in 2019. Vertical transmission (from mother to child) of HIV is significantly higher among women who acquire HIV during pregnancy, the postpartum period or during breastfeeding compared to HIV positive women who know their status before becoming pregnant. Among the 1,200,000 PBFW who acquired HIV in 2019, approximately 150,000 children acquired HIV in utero, during childbirth, or while breastfeeding.

Guidance on Preventing HIV Infection in PBFW

WHO Guidance on Oral PrEP in Pregnancy and Breastfeeding Women

In 2016, WHO released consolidated guidelines, which recommend the use of PrEP during pregnancy and breastfeeding. Based on findings that taking TDF-based PrEP during the first trimester of pregnancy was not associated with adverse outcomes for either mother or infant PrEP is recommended for:

  • Women taking PrEP who subsequently become pregnant and remain at substantial risk of HIV infection.
  • Pregnant or breastfeeding HIV-negative women living in settings with high HIV incidence who are at substantial risk of HIV acquisition.
  • Women whose HIV-positive partners are not virally suppressed, or don’t know their HIV status.

Additional resources available on PrEPWatch include clinical guidelines and a training package as well as a PrEP for PBFP demand generation resource package.

Country-Based Oral PrEP Guidelines for PBFW

Country Prevalence Among Women Total Fertility Rates Oral PrEP Approval PrEP Approval in PBFW Oral PrEP Guidance for PBFW
Australia & New Zealand <0.1 (Aus); <0.1 (NZ) 1.76 (Aus); 1.81 (NZ) 2017 2017 PrEP can be used in pregnancy and may be continued during breastfeeding
Canada 23.0 1.50 2016   TDF/FTC PrEP may be considered during pregnancy and breastfeeding after the benefits and risks have been discussed with the patient. However, in the case of an infected partner who is virally suppressed, PrEP is not recommended.
Eswatini 38 3.2 2017 2018 PrEP can be used throughout pregnancy and breastfeeding
France 0.3 1.92 2015   PrEP may be considered during pregnancy and breastfeeding after the benefits and risks have been discussed with the patient
Lesotho 30 3.14 2016   Not mentioned
Malawi 11 5.05 2018 N/A Not supported
South Africa 24 2.34 2015 2020 HIV negative women already taking PrEP, who become pregnant remain at substantial risk of HIV

HIV negative breastfeeding women who are at substantial risk of HIV or in serodiscordant relationships where there is no evidence of viral load suppression in the HIV positive partner

Pregnant women not on PrEP, considered to be at substantial risk of HIV may be referred to a HCP to discuss the potential risks and benefits of initiating PrEP during pregnancy
Uganda 7.7 5.6 2016 2016 Offered to the HIV seronegative partner in a sero-discordant relationship during attempts to conceive (part of a preconception care plan for the couple)

Special consideration for women and adolescents in discordant relations who desire to get pregnant
UK 1.0 1.79 2017 2017 Suggest continuation of PrEP if a woman is pregnant or breastfeeding when starting or becomes pregnant or initiates breastfeeding while using PrEP
USA 4.8 1.77 2012 2017 PrEP should be discussed with heterosexually-active women and men whose partners are known to have HIV infection (i.e., HIV-discordant couples) as one of several options to protect the uninfected partner during conception and pregnancy so that an informed decision can be made in awareness of what is known and unknown about benefits and risks of PrEP for mother and fetus
Zimbabwe 16 5.68 2013 2018 Pregnant women recognized as high-risk group and as part of sero-discordant couple such should be offered PrEP

*Please note that the above table of National HIV Guidelines are general frameworks for how a country addresses HIV within its borders. They may or may not include specific information related to PBFW and HIV.

Ongoing Research of PrEP Options in PBFW

Daily oral PrEP and the monthly Dapivirine Vaginal Ring (DVR) have proven to be potent and well-tolerated drugs against HIV in nonpregnant and non-breastfeeding women. Oral PrEP has been approved for use, including for pregnant and breastfeeding women in many countries. But some countries are unwilling to provide it to PBFP until more is known about its safety, despite WHO guidelines. As seen in the above country guidelines, many do not address PBFW as a population to receive PrEP. Meanwhile, the ring is a new product which is currently undergoing regulatory review, and additional clinical trials are testing its safety and efficacy during pregnancy and breastfeeding.

In order to address this dearth of information, the Microbicides Trial Network (MTN) has two ongoing studies, MTN-042 (DELIVER) and MTN-043 (B-PROTECTED) to evaluate the safety and acceptability of DVR and daily oral PrEP, specifically TDF/FTC (marketed as Truvada), in pregnant and breastfeeding women, respectively. The IMPAACT 2009 study also investigates the pharmacokinetics, feasibility, acceptability, and safety of oral PrEP for HIV prevention during pregnancy and postpartum in adolescent girls and young women (AGYW) and their infants. In addition, R4P 2021 hosted valuable research and insights on HIV prevention options in the pipeline during pregnancy and breastfeeding.

MTN-042/DELIVER

DELIVER is a Phase IIIb open-label study designed to examine the safety and acceptability of both oral PrEP, specifically TDF/FTC, as well as DVR among pregnant women. Launched in September 2020, this study enrolled approximately 750 women in Malawi, South Africa, Uganda, and Zimbabwe. All study participants were at different stages in their pregnancy. Each participant will use either oral PrEP or the ring until they give birth. Subsequently, the women will be followed for six months postpartum and their infants for one year after birth to assess safety and acceptability outcomes of the ring.

MTN-043/B-PROTECTED

B-PROTECTED is also a Phase IIIb open-label extension study, however, it is designed to examine the safety and acceptability of both oral PrEP, specifically TDF/FTC, and the ring amongst breastfeeding women. This study will enroll up to 200 newly breastfeeding mothers and their 6- to 12-week-old babies in Malawi, South Africa, Uganda, and Zimbabwe. Each of the women will be assigned to take either TDF/FTC or to use DVR for three months. Subsequently, they will be followed for an additional two weeks to measure concentrations of TDF/FTC and dapivirine in breastmilk, how much of each drug passes to the baby upon breastfeeding, and the health effects, if any, on infants.

Implementation Challenges and Opportunities

The launch of both DELIVER and B-PROTECTED can shed light on the impact that PrEP drugs have on PBFP and their infants. However, pregnant and breastfeeding people can benefit from PrEP now. Many people access healthcare during this period, making it an optimal time to reach people with HIV prevention services. Antenatal coverage (ANC) is high (more than 80%) in East and Southern Africa. ART has successfully been integrated into ANC, and this suggests integrating PrEP into ANC is feasible and acceptable. Working with community health workers and delivering PrEP in community settings can increase awareness of PrEP among pregnant and breastfeeding people.

Challenges remain, including lack of clear clinical guidelines at the national level or, where clear clinical guidelines exist, incomplete implementation. There is limited training for maternal and child health providers who primarily care for this population. There’s also a need for more robust systems to monitor adverse events tied to particular drugs. Stigma around PrEP use for pregnant and breastfeeding women are also a barrier to increasing PrEP use. Communication strategies designed to support PrEP use among PBFW are so far insufficient and must become a priority.

Oral PrEP is a Vital Prevention Option for PBFW: Make Access Easier

The field has long known that high rates of HIV incidence in pregnant and breastfeeding people, and high viral loads, can lead to high rates of vertical transmission and transmission to partners. Unfortunately, PrEP coverage is still low and not approved for PBFP in many countries, despite proven safety of the use of multiple ARVs for treatment in pregnant and lactating women living with HIV and growing implementation evidence of its safety and efficacy in HIV-negative women. Slow implementation is partially attributed to protectionist attitudes that prioritize infant health over a pregnant person’s health during pregnancy. This has contributed to delays in roll-out. It’s time to act now to make access easier:

  • Integrat PrEP into Prevention of Mother to Child Transmission (PMTCT) strategies at policy level.
  • Reach pregnant women with prevention early, during their first antenatal care visit.
  • Offer simplified and repeat testing (i.e. HIV self-testing) and self-care.
  • Advocate for PrEP delivery outside of the health facility and for multi-month prescriptions to make PrEP use more convenient.
  • Prepare to integrate Dapivirine Vaginal Ring and injectable cabotegravir into oral PrEP programs.

Clinical training guidelines on providing PrEP to pregnant and breastfeeding women can be found here.