Descovy for PrEP® (FTC/TAF)

Weight Change

This document is in response to your request for information regarding Descovy for PrEP® (emtricitabine/tenofovir alafenamide [FTC/TAF] for HIV-1 pre-exposure prophylaxis [PrEP]) and weight change. This response was developed according to principles of evidence-based medicine and only contains data from phase 3 clinical trials.

Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.

The full indication, important safety information, and boxed warnings are available at: www.gilead.com/-/media/files/pdfs/medicines/hiv/descovy/descovy_pi;
www.gilead.com/-/media/files/pdfs/medicines/hiv/truvada/truvada_pi.

Product Labeling1

Indications and Usage

HIV-1 PrEP

FTC/TAF is indicated in at-risk adults and adolescents weighing ≥35 kg for PrEP to reduce the risk of HIV-1 infection from sexual acquisition, excluding individuals at risk from receptive vaginal sex. Individuals must have a negative HIV-1 test immediately prior to initiating FTC/TAF for HIV-1 PrEP.

Limitations of Use: The indication does not include the use of FTC/TAF in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated.

Clinical Data on Weight Change With FTC/TAF

DISCOVER Study

Study design and demographics

DISCOVER (NCT02842086) is an ongoing, phase 3, randomized, double-blind, active‑controlled, multinational study in adult MSM and TGW without HIV that is evaluating the safety and efficacy of once-daily FTC/TAF (n=2694) vs FTC/TDF (n=2693) for HIV-1 PrEP. Eligible participants were randomly assigned (1:1) to receive either FTC/TAF or FTC/TDF with a corresponding placebo once daily. The primary outcome was the incidence of HIV-1 acquisition per 100 person-years after all participants had ≥48 weeks of follow-up and ≥50% of participants had 96 weeks of follow-up, with a pre-specified non‑inferiority margin of 1.62. All participants were unblinded after 96 weeks, and participants in both arms were offered the opportunity to continue on or switch to open-label FTC/TAF for an additional 48 weeks.2

Weight change

Baseline median BMI of participants in both arms was 25.3 kg/m2, and approximately 50% of participants had a BMI in the overweight/obese category (>25 kg/m2).3,4 Median weight changes for participants in the FTC/TAF vs FTC/TDF arm, respectively, were +1 kg vs 0 kg (P<0.001) at Week 48 and +1.7 kg vs +0.5 kg (P<0.001) at Week 96.3,5 A subgroup analysis assessed long-term outcomes of participants randomly assigned to FTC/TAF who continued on FTC/TAF in the open-label phase. The median weight change from baseline through Week 144 was +2.3 kg, which equated to a mean annualized increase in body weight of 0.83 kg per year.6

Overall, weight gain was observed in all participants across both arms, regardless of baseline PrEP use. Among baseline PrEP users, the median weight change from baseline to Week 96 was +2.3 kg in the FTC/TAF arm and +1.1 kg in the FTC/TDF arm (difference, 1.2 kg). Among participants with no baseline PrEP use, the median change in weight from baseline to Week 96 was +1.6 kg in the FTC/TAF arm and +0.4 kg in the FTC/TDF arm (difference, 1.2 kg).7

Retrospective Analysis of DISCOVER and iPrEx Studies8

Study design and demographics

A retrospective analysis compared weight changes in participants who received FTC/TAF for PrEP with those of participants who received placebo using data from DISCOVER and iPrEx, two randomized, double-blind, phase 3 clinical trials (N=6072). Eligible participants for each trial were assigned male at birth, aged ≥18 years, and negative for HIV-1 and had ≥1 behavior that increased the likelihood of acquiring HIV-1 (Figure 1). The main eligibility criteria for this analysis included ≥1 recorded body weight.

Figure 1. Retrospective Analysis of DISCOVER and iPrEx: Study Designs8

aFor iPrEx, the behaviors were the following: no condom use during anal intercourse with a male partner with either HIV or an unknown HIV status in the past 6 months; anal intercourse with >3 male partners in the past 6 months; exchange of money, gifts, shelter, or drugs for anal sex with a male partner in the last 6 months; sex with a male partner and diagnosis of a sexually transmitted infection in the last 6 months or at screening; having a sexual partner with HIV with whom condoms were not consistently used in the last 6 months. In DISCOVER, the behaviors were the following: condomless anal intercourse with ≥2 unique male partners with either HIV or an unknown HIV status in the last 12 weeks; a documented history of syphilis, rectal gonorrhea, or chlamydia in the last 24 weeks.

bNo participants in iPrEx received FTC/TDF before randomization.

Compared with participants in iPrEx, participants in DISCOVER were more likely to be White, be ≥36 years of age, have a BMI ≥27 kg/m2, and use more medications associated with weight gain (Table 1).

Table 1. Retrospective Analysis of DISCOVER and iPrEx: Baseline Demographics and Clinical Characteristics8

aParticipants who received FTC/TDF before baseline were counted in both columns and were subsequently randomly assigned to continue FTC/TDF or switch to FTC/TAF.

bIncluded American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, other race, and participants with Not Permitted designation when local regulations did not allow collection of race/ethnicity information.

cMost participants self-reported as “mixed race or other.”

dIncluded antidepressants/psychoanaleptics, antidiabetics, antiepileptics, antihistamines, antipsychotics, contraceptives, corticosteroids, beta-androgenic blockers, and insulin.

Results

Among participants with no prior use of FTC/TDF, there was no significant difference in mean weight change from baseline between participants who received FTC/TAF in DISCOVER and placebo in iPrEx at Week 24 (mean difference, +0.7 kg), Week 48 (+0.44), Week 72 (+0.13), or Week 96 (+0.53; each, P=0.1; Figure 2).

Figure 2. Retrospective Analysis: Estimated Mean Weight Changea From Baseline to Week 96 in Participants Who Received FTC/TAF in DISCOVER or Placebo in iPrEx8

aData were adjusted for baseline age, country of enrollment, diabetes status, non-fasting glucose, eGFR, ALT levels, race, height, use of medications associated with weight change at baseline and during the trial, and weight.

Note: Solid lines represent means, and shaded areas represent 95% CIs.

Among participants with no prior FTC/TDF use, similar proportions of participants who received FTC/TAF in DISCOVER and placebo in iPrEx had large increases in body weight at 48 weeks (Table 2).

Table 2. Retrospective Analysis: Top Percentiles of Weight Changea From Baseline to Week 48 in Participants With No Prior FTC/TDF Use Who Received FTC/TAF in DISCOVER or Placebo in iPrEx8

aData were adjusted for baseline age, country of enrollment, diabetes status, non-fasting glucose, eGFR, ALT levels, race, height, use of medications associated with weight change at baseline and during the trial, and weight.

Among participants with no prior FTC/TDF use, the estimated mean weight change from baseline was similar between those who received FTC/TDF in DISCOVER or iPrEx (Figure 3).

Figure 3. Retrospective Analysis: Estimated Mean Weight Changea From Baseline to Week 96 in Participants With No Prior FTC/TDF Use Who Received FTC/TDF in DISCOVER or iPrEx8

aData were adjusted for baseline age, country of enrollment, diabetes status, non-fasting glucose, eGFR, ALT levels, race, height, use of medications associated with weight change at baseline and during the trial, and weight.

Note: Solid lines represent means, and shaded areas represent 95% CIs.

Among participants in DISCOVER with prior FTC/TDF use who switched to FTC/TAF at baseline, the mean weight gain was similar to that in participants in iPrEx with no prior FTC/TDF use who received placebo, with a mean (95% CI) between-group difference of +0.46 (0.02–0.9) kg at Week 24, +1.15 (0.53–1.77) kg at Week 48, +0.63 (-0.16 to 1.42) kg at Week 72, and +1.74 (0.78–2.7) kg at Week 96 (Figure 4).

Figure 4. Retrospective Analysis: Estimated Mean Weight Changea in Participants With Prior FTC/TDF Use Who Switched to FTC/TAF in DISCOVER vs Received Placebo in iPrEx8

aData were adjusted for baseline age, country of enrollment, diabetes status, non-fasting glucose, eGFR, ALT levels, race, height, use of medications associated with weight change at baseline and during the trial, and weight.

Note: Solid lines represent means, and shaded areas represent 95% CIs.

References

1. Enclosed. Gilead Sciences Inc, DESCOVY® (emtricitabine and tenofovir alafenamide) tablets, for oral use. U. S. Prescribing Information. Foster City, CA.

2. Mayer KH, Molina JM, Thompson MA, et al. Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet. 2020;396(10246):239-254.

3. Ogbuagu O, Ruane PJ, Podzamczer D, et al. Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet HIV. 2021;8:e397-e407.

4. Ogbuagu O, Ruane PJ, Podzamczer D, et al. Supplementary appendix Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet HIV. 2021;8(7):1-21.

5. Ruane P, Clarke A, Post FA, et al. Phase 3 Randomized, Controlled DISCOVER Study of Daily F/TAF or F/TDF for HIV Pre-exposure Prophylaxis: Week 96 Results [Poster PE3/16]. Paper presented at: 17th European AIDS Conference; 06-09 November, 2019; Basel, Switzerland.

6. Ramgopal M, Ruane P, Shalit P, et al. Long-term Outcomes of Participants on F/TAF for Pre-Exposure Prophylaxis: Results for 144 Weeks of Follow-Up in the DISCOVER Trial [Poster 854]. Paper presented at: IDWeek Virtual; 29 Sept-03 Oct, 2021.

7. Campbell T, Clarke A, Trottier B, et al. Safety and Efficacy of F/TAF and F/TDF for PrEP in DISCOVER Participants Taking F/TDF for PrEP at Baseline [Poster 995]. Paper presented at: IDWeek Virtual; 21-25 October, 2020.

8. Glidden D, Whiteman A, Tian Y, Marongiu A, Gruber J, Cohen C. Weight Change on F/TAF Versus Placebo: Using Common F/TDF Groups to Bridge Data Across Clinical Trials. [Poster #892]. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 9–12, 2025; San Francisco, CA.

Abbreviations

FTC=emtricitabine
MSM=men who have sex with men

PrEP=pre-exposure prophylaxis
TAF=tenofovir alafenamide

TDF=tenofovir disoproxil fumarate
TGW=transgender women
 

Product Label

For the full indication, important safety information, and boxed warning(s), please refer to the Descovy and Truvada US Prescribing Information available at:
www.gilead.com/-/media/files/pdfs/medicines/hiv/descovy/descovy_pi;

www.gilead.com/-/media/files/pdfs/medicines/hiv/truvada/truvada_pi.

Follow-Up

For any additional questions, please contact Gilead Medical Information at:

☎ 1-866-MEDI-GSI (1-866-633-4474) or   www.askgileadmedical.com

Adverse Event Reporting

Please report all adverse events to:

Gilead Global Patient Safety ☎ 1-800-445-3235, option 3 or
 www.gilead.com/utility/contact/report-an-adverse-event

FDA MedWatch Program by ☎ 1-800-FDA-1088 or MedWatch, FDA, 5600 Fishers Ln, Rockville, MD 20852 or   www.accessdata.fda.gov/scripts/medwatch

Data Privacy

The Medical Information service at Gilead Sciences may collect, store, and use your personal information to provide a response to your medical request. We may share your information with other Gilead Sciences colleagues to ensure that your request is addressed appropriately. If you report an adverse event or concern about the quality of a Gilead or Kite product, we will need to use the information you have given us in order to meet our regulatory requirements in relation to the safety of our medicines.

It may be necessary for us to share your information with Gilead’s affiliates, business partners, service providers, and regulatory authorities located in countries besides your own. Gilead Sciences has implemented measures to protect the personal information you provide. Please see the Gilead Privacy Statement (www.gilead.com/privacy-statements) for more information about how Gilead handles your personal information and your rights. If you have any further questions about the use of your personal information, please contact gilead.privacy@gilead.com.

DESCOVY, DESCOVY for PrEP, TRUVADA, GILEAD, and the GILEAD logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
© 2026 Gilead Sciences, Inc.