What is the clinical evidence supporting efficacy of off-label Descovy for PrEP in women?

Comment by InpharmD Researcher

Available clinical evidence does not establish the efficacy of emtricitabine/tenofovir alafenamide (F/TAF; Descovy) for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) in women at risk through receptive vaginal exposure. Prescribing information and Centers for Disease Control and Prevention (CDC) guidance note that effectiveness in this population has not been evaluated, and existing efficacy data are derived primarily from studies in men who have sex with men and transgender women. Additionally, a phase I randomized trial in women (see Table 1) evaluated pharmacokinetics and safety only and included no clinical efficacy endpoints, leaving HIV prevention benefit in this population unestablished.

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Background

A 2021 expert review evaluating emtricitabine/tenofovir alafenamide (F/TAF) for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) reported that clinical efficacy data supporting its use are derived primarily from the DISCOVER trial, which enrolled men who have sex with men and transgender women and demonstrated non-inferiority of F/TAF compared with F/TDF for prevention of HIV acquisition via anal sex; however, the review explicitly states that cisgender women were not included and that efficacy for vaginal exposure has not been established. The author notes that F/TAF has yet to be tested in populations at risk through vaginal intercourse and that safety and efficacy in cis-women remain to be investigated, highlighting an absence of direct clinical evidence supporting efficacy in women. The article further emphasizes that available clinical trial data address sexual transmission through anal exposure only, and that clinical trials specifically evaluating prevention in women are still needed. [1]

Recent clinical guidance from the Centers for Disease Control and Prevention (CDC) describes available PrEP regimens and clarifies the current evidence base supporting their use across populations. The CDC notes that emtricitabine/tenofovir alafenamide (F/TAF; Descovy®) is recommended for prevention of HIV through sexual transmission, excluding individuals likely to acquire HIV through receptive vaginal sex, and explicitly states that F/TAF has not yet been studied for HIV prevention among people assigned female at birth who could acquire HIV via receptive vaginal exposure. Consequently, for cisgender women or others at risk through receptive vaginal sex, recommended PrEP options include daily oral emtricitabine/tenofovir disoproxil fumarate (F/TDF) or long-acting injectable cabotegravir rather than F/TAF. These recommendations reflect the absence of clinical efficacy data in this population rather than demonstrated lack of effectiveness, and the CDC guidance does not cite clinical trials evaluating Descovy for PrEP efficacy in women with receptive vaginal exposure. [2]

References: [1] Mesplède T. Evaluating the combination of emtricitabine/ tenofovir alafenamide fumarate to reduce the risk of sexually acquired HIV-1-infection in at-risk adults. Expert Opin Pharmacother. 2021;22(10):1245-1251. doi:10.1080/14656566.2021.1902504
[2] Centers for Disease Control and Prevention. Clinical guidance for PrEP. HIV Nexus. Updated February 10, 2025. Accessed February 11, 2026. https://www.cdc.gov/hivnexus/hcp/prep/index.html
Relevant Prescribing Information

Indications and Usage [3]
Limitations of Use:
The indication does not include use of DESCOVY in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated.

References: [3] Descovy (emtricitabine and tenofovir alafenamide tablet). Prescribing information. Gilead Sciences, Inc.; 2025.
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What is the clinical evidence supporting efficacy of off-label Descovy for PrEP in women?

Level of evidence

D - Case reports or unreliable data  Read more→


Please see Table 1 for your response.

Safety and Pharmacokinetics of a Tenofovir Alafenamide Fumarate-Emtricitabine based Oral Antiretroviral Regimen for Prevention of HIV Acquisition in Women: A Randomized Controlled Trial
Design

Phase I, prospective, interventional, randomized study

N= 99
Objective To assess the multi-compartmental pharmacokinetics and safety of F/TAF versus F/TDF among HIV uninfected women
Study Groups

F/TDF (n= 24)

F/TAF25 (n= 24)

F/TAF10 (n= 26)
Inclusion Criteria Healthy, non-pregnant, HIV-uninfected women aged 18-50 years with regular menstrual cycles, a BMI ≥ 18 and < 35 kg/m2, and who were either sexually abstinent or in a monogamous relationship with a healthy partner
Exclusion Criteria Not specified
Methods Participants were randomized to receive either F/TDF (200mg/300mg), F/TAF25 (200mg/25mg), or F/TAF10 (200mg/10mg). The study included a single dose phase (SDP) and a multiple dose phase (MDP) with 14 daily doses. Pharmacokinetics were assessed in plasma, PBMCs, and cervicovaginal and rectal fluids and tissues. Safety was evaluated by monitoring treatment-emergent adverse events (TEAEs).
Duration October 2016 to November 2017
Outcome Measures

Primary: Multi-compartmental pharmacokinetics of F/TAF and F/TDF

Secondary: Safety, measured by treatment-emergent adverse events (TEAEs)
Baseline Characteristics   F/TAF (200/25) (n= 12) F/TDF (200/300) (n= 12) F/TAF (200/10) (n= 26) F/TAF (200/25) (n= 24) F/TDF (200/300) (n= 25)
Age, years (SD) 34.1 (7) 37.7 (7) 33.2 (7) 34.6 (8) 32.8 (9)
Body-mass index, kg/m2 (SD) 28.3 (4) 26.7 (4) 26.7 (4) 27.0 (4) 26.8 (4)
White 6 (50%) 10 (83%) 18 (69%) 20 (83%) 18 (72%)
Results   F/TAF (200/25) (n=24) F/TDF (200/300) (n=25) p-value
Gastrointestinal TEAEs 11.5% 44.0% 0.016
Nausea 8.3% 32.0% 0.020
TFV-DP in PBMCs, fmol/106 cells (Day 14) 15,215 (8700, 42,689) 2,498 (562, 3993) <0.001
Adverse Events Gastrointestinal adverse events occurred more frequently in F/TDF users (44.0%) than in either F/TAF group (11.5% and 12.0%)
Study Author Conclusions F/TAF was safe and well-tolerated, with higher TFV-DP concentrations in PBMCs and similar or higher concentrations in female genital tract tissues compared to F/TDF, supporting its potential as a new PrEP combination for women
Critique The study provides valuable insights into the pharmacokinetics and safety of F/TAF versus F/TDF, but the short dosing duration and lack of randomization to collection time points between clinical sites may limit the interpretation of tissue PK estimates. Additionally, the study's open-label design could introduce bias. More importantly, no clinical endpoints were analyzed, thus clinical significance of the findings above are uncertain. 

 

References:
[1] Thurman AR, Schwartz JL, Cottrell ML, et al. Safety and Pharmacokinetics of a Tenofovir Alafenamide Fumarate-Emtricitabine based Oral Antiretroviral Regimen for Prevention of HIV Acquisition in Women: A Randomized Controlled Trial. EClinicalMedicine. 2021;36:100893. Published 2021 May 23. doi:10.1016/j.eclinm.2021.100893