HIV PrEP in Pregnancy: Closing the Evidence Gap

Key Takeaways

• Pregnancy and lactation remain major HIV PrEP evidence gaps despite elevated HIV prevention need, with approximately one-quarter of vertical HIV transmissions linked to infections acquired during pregnancy and lactation.
• HIV therapy evidence in pregnancy and lactation has often lagged after first approval, with an average 4.4-year delay before study in these populations and an estimated 6-year delay for pregnancy pharmacokinetic data.
• The working group endorsed a shift from presumptive exclusion of pregnant and lactating women toward a protection-through-research framework centered on equitable inclusion.
• Fragmented surveillance systems, nonstandardized data, and poor interoperability were described as persistent barriers, alongside calls for earlier pregnancy-specific evidence generation, more harmonized regulation, and stronger community engagement.

Pregnancy and the postpartum period carry high HIV prevention need, yet product-specific pre-exposure prophylaxis (PrEP) evidence often remains sparse when options reach practice. That gap persists within an epidemic that still included 1.3 million new human immunodeficiency virus (HIV) infections in 2023, while PrEP use remained well below global targets. Regulators, researchers, industry representatives, and community stakeholders set out to examine why pregnancy- and lactation-specific evidence continues to arrive late and unevenly across development and post-approval monitoring.

Regulators from the United States, Europe, and Africa met with representatives from international organizations, academia, industry, and community and advocacy groups in a multisectoral working group. Convened through the Forum for Collaborative Research to advance pre- and post-approval data collection on PrEP use in pregnant and lactating women, the group met nine times between January 2024 and February 2025 and co-organized a scientific symposium in Lima, Peru, from 6 to 10 October 2024. No formal Delphi-style consensus process or evidence grading was applied, so the recommendations reflected structured discussion across stakeholders rather than a graded consensus statement.

Women remained underrepresented in HIV research, with median female participation of 19.2% in antiretroviral (ARV) studies, 38.1% in vaccine trials, and 11.1% in cure research. HIV therapies were studied during pregnancy and lactation an average of 4.4 years after first regulatory approval, and pregnancy pharmacokinetic data were delayed by an estimated 6 years. The working group linked those gaps to ethical reframing from vulnerable to complex populations needing protection through research, limited reproductive safety and pharmacokinetic evidence, minimal community input, variable regulatory expectations, weak sponsor incentives, and limited surveillance capacity. As contextual product examples, the authors described oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as the most studied option, cited later pregnancy and lactation safety examples for long-acting cabotegravir (CAB-LA) and the dapivirine vaginal ring (DVR), and presented lenacapavir (LEN) as a more deliberate inclusion example, noting 100% efficacy against HIV acquisition in PURPOSE 1 and 193 pregnancies among participants randomized to LEN at interim analysis.

These recommendations reflected working group discussion rather than a randomized comparative trial or a formal guideline process, and the absence of formal evidence grading or Delphi consensus limits how definitively they can be framed. The authors also argued that controlled trials may miss rare, long-term, and real-world outcomes after PrEP exposure during pregnancy and lactation. Infant developmental follow-up after in utero or breastfeeding exposure remains sparse, with few studies extending beyond 1 year, which is why the group tied stronger post-approval surveillance to coordinated ethics, regulation, surveillance infrastructure, and community partnership rather than to late backfilling after approval alone.

The working group concluded that reducing HIV PrEP evidence gaps in pregnancy and lactation depends on earlier inclusion across development, labeling, and surveillance. Community participation, standardized data systems, and pregnancy-specific safety and pharmacology planning were presented as parts of the same evidence-generation strategy. More equitable evidence generation is still needed if pregnancy and lactation are to be addressed as routine parts of HIV prevention research rather than deferred populations.

Clinician Questions

How long after first regulatory approval were HIV therapies typically studied in pregnancy and lactation?

The working group reported that HIV therapies were studied during pregnancy and lactation an average of 4.4 years after first regulatory approval, with pregnancy pharmacokinetic data delayed by an estimated 6 years, underscoring a persistent HIV PrEP evidence gap.

What does the protection-through-research framework mean for HIV PrEP studies in pregnancy and lactation?

According to the authors, protection through research means moving away from presumptive exclusion of pregnant and lactating women as vulnerable populations and toward equitable inclusion supported by earlier reproductive safety studies and pregnancy-specific pharmacokinetic evidence generation.

What surveillance gaps did the working group identify for PrEP use during pregnancy and lactation?

The authors described fragmented post-approval systems, nonstandardized data, poor interoperability across research platforms, electronic health records, and national systems, and limited capacity for comprehensive surveillance of PrEP use during pregnancy and lactation. Maternal, pregnancy, infant, and longer-term developmental outcomes after in utero or breastfeeding exposure also remained insufficiently studied.