Safety review of tenofovir disoproxil fumarate/emtricitabine pre-exposure prophylaxis for pregnant women at risk of HIV infection

ABSTRACT

Introduction: Pregnancy is a period of elevated HIV risk in high-burden settings, motivating the need for prevention tools that are both safe for use and effective during pregnancy. Oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) is recommended by the World Health Organization, including for pregnant and postpartum women at substantial risk of HIV infection. Although TDF use during pregnancy appears generally safe, data on PrEP use during pregnancy remain limited.

Areas covered: We provide an overview of the clinical pharmacology and efficacy of daily TDF-based PrEP and summarize current evidence on the safety of PrEP use by pregnant HIV-uninfected women. We synthesize relevant studies assessing pregnancy outcomes among pregnant women who are living with HIV (WLHIV) and using TDF-based therapy. Finally, we make comparison to the safety profiles of other emerging HIV prevention options.

Expert opinion: The current evidence indicates that TDF/FTC PrEP use is not associated with increased risk of adverse pregnancy and early infant growth outcomes. While safety data are generally reassuring, there is need for continued accrual of data on growth and pregnancy outcomes in PrEP research, implementation projects, and controlled pharmacokinetic studies to support current evidence and to understand concentration–efficacy relationship in pregnant women.

KEYWORDS:

• Tenofovir disoproxil fumarate
• PrEP
• HIV prevention
• safety
• pregnancy
• women

Article highlights

• Safety of TDF/FTC use during pregnancy has been evaluated in multiple completed PrEP efficacy trials and real-world PrEP implementation projects.

• Women who have been exposed to TDF/FTC experience similar frequencies of pregnancy, perinatal, and early childhood outcomes compared to unexposed women.

• Studies of women living with HIV who have been given treatment regimens containing TDF/FTC support these findings.

• Safety data among pregnant women are limited for other PrEP products nearing the market, including longer-acting vaginal ring and injectable options.

• Active inclusion of pregnant women in future evaluations of oral TDF/TDF use and other PrEP products is critical to addressing evidence gaps and promoting equity.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the National Institutes of Health institutional training grant [grant number T32AI007140] and the US National Institute of Mental Health [grant numbers R00MH118134 and R01MH123267].