What are the FDA-approved Pre-Exposure Prophylaxis (PrEP) options for pregnant individuals at risk of Human Immunodeficiency Virus (HIV) exposure?

FDA-Approved HIV PrEP Options During Pregnancy

Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300mg/200mg is the FDA-approved and recommended PrEP regimen for pregnant women at substantial risk of HIV acquisition, and pregnancy should not preclude its use. 1, 2, 3

Primary Recommendation: TDF/FTC (Truvada)

• TDF/FTC is the only FDA-approved PrEP regimen with sufficient safety data supporting use during pregnancy. 1, 2, 3
• The standard dosing remains 300mg TDF/200mg FTC once daily, identical to non-pregnant individuals. 2, 3
• Studies examining TDF/FTC use in pregnant women living with HIV have not shown evidence of adverse fetal effects. 1
• The Antiretroviral Pregnancy Registry data from over 1,330 exposures to TAF-containing regimens showed birth defect rates (3.9% first trimester, 4.8% second/third trimester) comparable to the general population background rate of 2.7%. 4

Clinical Rationale for Use During Pregnancy

• Pregnancy itself increases HIV acquisition risk compared to non-pregnant women, making PrEP particularly valuable during this period. 1, 2
• For women at very high risk of HIV acquisition, the benefits of continuing TDF/FTC PrEP during pregnancy outweigh potential risks. 1
• PrEP is especially valuable for HIV-negative partners in serodiscordant couples attempting to conceive. 1

Pre-Initiation Requirements

Before prescribing PrEP to pregnant women, confirm:

• HIV-negative status using a fourth-generation antigen-antibody assay 2, 3
• Creatinine clearance ≥60 mL/min using Cockcroft-Gault formula 2, 3
• Hepatitis B surface antigen (HBsAg) status 3
• Comprehensive STI screening 3
• Assessment for acute HIV infection symptoms or recent unprotected sex with HIV-positive partner 2

Shared Decision-Making and Counseling

Healthcare providers must discuss currently available information regarding potential risks and benefits of continuing PrEP with pregnant women to enable informed decision-making. 1, 2

Key counseling points include:

• Safety data for infants exposed during pregnancy is incomplete, though no harm has been reported to date 2
• PrEP is not 100% effective and does not prevent other STIs 2
• The known benefits of preventing HIV acquisition during pregnancy likely outweigh potential risks for women at substantial risk 2
• Efficacy is highly dependent on adherence to daily doses 1, 3

Monitoring During Pregnancy

Every 2-3 months, perform:

• HIV antibody/antigen testing with documented negative result 1, 2, 3
• Adherence assessment and support 1, 2, 3
• STI screening 2, 3
• Renal function monitoring (creatinine clearance) 3

Prescribe no more than a 90-day supply, renewable only after confirming continued HIV-negative status. 2

Pregnancy Registry Enrollment

If a woman chooses to take PrEP while pregnant, providers are encouraged to prospectively and anonymously submit information to the Antiretroviral Pregnancy Registry by calling 1-800-258-4263. 1, 4

What NOT to Use During Pregnancy

• Tenofovir alafenamide/emtricitabine (TAF/FTC): Insufficient efficacy data exists for vaginal exposure in cisgender women, making it inappropriate as first-line for pregnant women. 3
• On-demand (2-1-1) dosing: This strategy is NOT recommended for women, as daily dosing is mandatory for vaginal exposure protection. 3
• Efavirenz (EFV): Not recommended during pregnancy due to teratogenic effects observed in primate studies. 5
• Stavudine (d4T) + didanosine (ddI) combination: Avoid due to reports of fatal lactic acidosis in pregnant women. 5

Important Safety Considerations

• TDF-based PrEP causes 1-1.5% bone mineral density loss at 48 weeks, which returns to baseline upon discontinuation. 2
• TDF-based PrEP is not recommended in patients with pre-existing osteopenia or osteoporosis. 2
• Tenofovir plasma exposures are reduced during pregnancy (25-26% lower in third trimester versus postpartum), but standard dosing remains appropriate for most pregnant women. 6, 7
• Therapeutic drug monitoring with dose adjustment should be considered in pregnant women with high weight (>90 kg) or inadequate HIV RNA response if they were already HIV-positive. 6

Postpartum and Breastfeeding

• Breastfeeding while taking tenofovir-based PrEP is considered safe, with very low concentrations of the drug found in breast milk. 2, 4
• TDF/FTC is safe during breastfeeding and should be continued if HIV risk persists. 3
• Data from published literature report the presence of TAF and tenofovir in human milk without reported adverse effects on breastfed children. 4

Critical Pitfalls to Avoid

• Do not prescribe PrEP without confirming HIV-negative status, as resistance can develop if prescribed during acute HIV infection. 3
• Do not deny PrEP to a pregnant woman solely on the basis of pregnancy. 5
• Do not forget that protection is not immediate—counsel about the 7-day lead-in period for women before full protection is achieved. 3
• Do not discontinue PrEP during pregnancy without performing HIV testing to confirm whether infection has occurred. 2
• If HIV-positive status is discovered, establish immediate linkage to HIV care and resistance testing. 2

Recent High-Quality Evidence

The 2023 CAP016 randomized controlled trial (n=540 pregnant women in South Africa) demonstrated that immediate PrEP initiation during pregnancy was non-inferior to deferred PrEP for preterm birth and small for gestational age infants, with a risk difference of -4.7% for preterm birth (90% CI -10.7 to 1.2). 8 This provides the strongest recent evidence supporting PrEP safety during pregnancy, though some secondary outcomes (very preterm birth, low birthweight, stillbirth) had upper confidence interval limits exceeding non-inferiority margins, warranting continued monitoring. 8