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.

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

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 Changes With FTC/TAF

DISCOVER: Once Daily FTC/TAF vs FTC/TDF for HIV-1 PrEP in MSM and TGW

Study design and demographics

DISCOVER (NCT02842086) is an ongoing, phase 3, randomized, double-blind, active‑controlled, multinational study in 5387 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), both of which are fixed-dose combination products administered once daily for HIV-1 PrEP. Participants are aged ≥18 years, negative for HIV and HBV, have an eGFR of ≥60 mL/min, and are at high risk of sexual acquisition of HIV (defined as ≥2 episodes of condomless anal intercourse with ≥2 unique male partners with HIV or are of unknown HIV status within the previous 12 weeks, or have a documented history of syphilis, rectal gonorrhea, or rectal chlamydia in the previous 24 weeks). Prior use of FTC/TDF for HIV-1 PrEP is allowed.2,3

Eligible participants were randomized 1:1 to receive either FTC/TAF 200/25 mg or FTC/TDF 200/300 mg with a corresponding placebo once daily. Follow-up visits occurred at baseline and every 12 weeks and included the following: comprehensive screenings for sexually transmitted infections and HIV; assessments of AEs, renal function, sexual behavior, adherence (measured by pill counts), questionnaires, plasma TFV levels, and dried blood spot TFV-diphosphate levels. The primary measured outcome was the incidence of HIV-1 infection 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 that represented the upper bound of the 95% CI for the measured incidence rate ratio of FTC/TAF over FTC/TDF. All participants were unblinded after 96 weeks, and participants in both arms were offered the opportunity to continue on or switch to an ongoing, open-label, once-daily FTC/TAF for an additional 48 weeks.3

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).4,5 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 96.4,6 A subgroup analysis assessed long-term FTC/TAF outcomes based on Week 144 results in participants who were randomly assigned to receive FTC/TAF at study enrollment and continued on FTC/TAF through Week 144, including 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.7

Overall, weight gain was observed in all participants across both arms regardless of baseline PrEP use. Weight gain differences between the two treatment arms were similar when comparing prior baseline PrEP use to no baseline PrEP use (Figure 1).8

Figure 1. Median Weight Change From Baseline to Week 96 in Participants With Baseline PrEP vs No Baseline PrEP8

TDF and weight loss

Weight decrease as an AE was reported in >2% of participants without HIV who received FTC/TDF, with an incidence greater than placebo in PrEP trials.9 Findings from two phase 3, randomized, double-blind studies suggested a mild weight‑suppressive effect with the use of TDF as a component of FTC/TDF for HIV PrEP.10-12 In a metabolic substudy of the iPrEx study, participants in the FTC/TDF arm gained less weight than those in the placebo arm. At Week 24, the median difference in net weight of FTC/TDF compared with placebo was ‑0.8% (95% CI: ‑1.5% to -0.1%; P=0.02).11 In comparison, there was 1 kg of weight gain per year among average Americans aged 20 to 40 years old seen in the National Health and Nutrition Examination Survey and the Coronary Artery Risk Development in Young Adults study.13

References

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

2. Ogbuagu O, Podzamczer D, Salazar LC, et al. Longer Term Efficacy and Safety of F/TAF and F/TDF For HIV PrEP: DISCOVER Trial Week 96 Results [Presentation]. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); 08-11 March, 2020; Boston, MA.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. Enclosed. Gilead Sciences Inc, TRUVADA® (emtricitabine/tenofovir disoproxil fumarate) tablets, for oral use. U.S. Prescribing Information. Foster City, CA.

10. Sax PE, Erlandson KM, Lake JE, et al. Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials. Clin Infect Dis. 2020;71(6):1379-1389. https://www.ncbi.nlm.nih.gov/pubmed/31606734

11. Glidden D, Mulligan K, McMahan V, et al. Metabolic Effects of Preexposure Prophylaxis With Coformulated Tenofovir Disoproxil Fumarate and Emtricitabine. . Clinical Infectious Diseases (CID). 2018.

12. Spinner CD, Brunetta J, Shalit P, et al. DISCOVER STUDY for HIV Pre-Exposure Prophylaxis: F/TAF has a more Rapid Onset and Longer Sustained Duration of HIV Protection Compared with F/TDF [Presentation]. Paper presented at: IAS 2019; 21-24 July, 2019; Mexico City, Mexico.

13. Hill JO, Wyatt HR, Reed GW, Peters JC. Obesity and the environment: where do we go from here? Science. 2003;299(5608):853-855. https://www.ncbi.nlm.nih.gov/pubmed/12574618

Abbreviations

AE=adverse event
FTC=emtricitabine
MSM=men who have sex with men
PrEP=pre-exposure prophylaxis
TAF=tenofovir alafenamide
TDF=tenofovir disoproxil fumarate

TFV=tenofovir
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

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