Yeztugo® (lenacapavir)

Use in Individuals Switching from CAB for HIV-1 PrEP

This document is in response to your request for information regarding Yeztugo® (lenacapavir [LEN]) and its use in individuals switching from cabotegravir for HIV-1 pre-exposure prophylaxis intramuscular injections every 2 months (Q2M IM CAB for PrEP).

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 use of FTC/TAF for prevention of HIV-1 in individuals at risk of HIV-1 from receptive vaginal sex is investigational and has not been approved by any regulatory authority. The full indication, important safety information, and boxed warning(s) are available at:
www.gilead.com/-/media/files/pdfs/medicines/hiv/yeztugo/yeztugo_pi;
www.gilead.com/-/media/files/pdfs/medicines/hiv/descovy/descovy_pi;
www.gilead.com/-/media/files/pdfs/medicines/hiv/truvada/truvada_pi.

Summary

Product Labeling

LEN is indicated for PrEP to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating LEN.1

Available Data

• There is no clinical data in HIV-negative individuals switching from Q2M IM CAB for PrEP to LEN for PrEP.
• There are no clinically significant DDIs expected with concurrent use of LEN and Q2M IM CAB for PrEP because they have different mechanisms of action and metabolic pathways.1,2
• There is no contraindication for switching to LEN immediately.1 LEN may be initiated in appropriate individuals.

Product Labeling1

Warning: Risk of Drug Resistance with Use of LEN for HIV-1 PrEP in Undiagnosed HIV-1 Infection

Individuals must be tested for HIV-1 infection prior to initiating LEN, and with each subsequent injection of LEN, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. Drug-resistant HIV-1 variants have been identified with use of LEN by individuals with undiagnosed HIV-1 infection. Do not initiate LEN unless negative infection status is confirmed. Individuals who acquire HIV-1 while receiving LEN must transition to a complete HIV-1 treatment regimen.

Indications and Usage

LEN is indicated for PrEP to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating PrEP.

Recommended Dosage

The LEN dosing schedule in adults and adolescents weighing at least 35 kg consists of a required initiation dosing (subcutaneous injections and oral tablets) followed by once every 6-months continuation dosing (subcutaneous injections; Table 1). LEN oral tablets may be taken with or without food.

Table 1. Dosing Schedule for LEN Initiation and Continuation in

Adults and Adolescents Weighing ≥35 kg

a The complete initiation dosing schedule, consisting of subcutaneous injections and oral tablets, is required; the efficacy of LEN has only been established with this dosing schedule.

b From the date of the last injection.

Clinical Data

PURPOSE 1 is an ongoing, phase 3, double-blind, randomized study evaluating the efficacy and safety of twice-yearly SUBQ LEN (n=2134) and once-daily oral FTC/TAF (n=2136) or FTC/TDF (active control; n=1068) for HIV-1 PrEP in 5338 cisgender women and adolescent girls (16–25 years old) across South Africa and Uganda. Participants receiving PrEP in the 3 months prior to screening were excluded from the study.3

PURPOSE 2 is an ongoing, phase 3, double-blind, randomized study evaluating the efficacy and safety of twice-yearly SUBQ LEN or once-daily oral FTC/TDF for HIV-1 PrEP in cisgender gay, bisexual, and other men, TGW, TGM, and GNB individuals in Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the US who have condomless receptive anal sex with partners assigned male at birth (N=3265). Participants receiving PrEP in the 3 months prior to screening were excluded from the study.4  

PK DDI Evaluation

There are no clinically significant DDIs expected with concurrent use of LEN and Q2M IM CAB for PrEP because they have different mechanisms of action and metabolic pathways.1,2 Relevant LEN PK data presented in Table 2 below. For more information about Q2M IM CAB for PrEP, please refer to its product labeling.2

LEN PK

Table 2. LEN DDI Potential1,5

a Combined P gp, UGT1A1, and strong CYP3A inhibitors may significantly increase plasma concentrations of     LEN. Concomitant administration of LEN with these inhibitors is not recommended.

b Drugs that are strong or moderate inducers of CYP3A may significantly decrease plasma concentrations of LEN, which may result in reduced effectiveness of LEN. Therefore, dosage modifications (supplemental doses) of LEN are recommended when initiating strong or moderate CYP3A inducers. Please refer to Section 2.5, Dosage Modifications for Co-administration with Strong or Moderate CYP3A Inducers, of the Yeztugo US Prescribing Information for more information.

Literature Search

A literature search was conducted in Ovid MEDLINE and Embase databases for studies published between 1946 and June 18, 2025 using search terms that included Yeztugo, lenacapavir, PrEP, cabotegravir, switch and related search terms. No relevant citations were found.

References

1. Enclosed, Gilead Sciences Inc. YEZTUGO® (lenacapavir) tablets, for oral use. YEZTUGO® (lenacapavir) injection, for subcutaneous use. U.S. Prescribing Information. Foster City, CA.
2. APRETUDE, ViiV Healthcare. APRETUDE (cabotegravir extended-release injectable suspension), for intramuscular use. U. S. Prescribing Information. Durham, NC. Revised: September. 2024.
3. Bekker LG, Das M, Abdool Karim Q, et al. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. N Engl J Med. 2024;391(13):1179-1192.
4. Kelley CF, Acevedo-Quinones M, Agwu AL, et al. Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons. N Engl J Med. 2024.
5. Lutz J. CLINICAL EVALUATION OF DRUG INTERACTIONS WITH ORAL LENACAPAVIR AND PROBE DRUGS [Presentation]. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 6-10, 2021; Virtual.

Abbreviations

BCRP=breast cancer resistance protein CAB=cabotegravir
DDI=drug-drug interaction
FTC=emtricitabine
GNB=gender non-binary
LEN=lenacapavir
MATE=multidrug and toxin extrusion protein
NA=not applicable
OATP=organic anion transporting polypeptide
OCT=organic cation transporter
P-gp=P-glycoprotein
PK=pharmacokinetic(s)
PrEP=pre-exposure prophylaxis

Q2M=every 2 months
SUBQ=subcutaneous
TAF=tenofovir alafenamide
TDF=tenofovir disoproxil fumarate
TGM=transgender men
TGW=transgender women

Product Label

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

YEZTUGO, DESCOVY, DESCOVY for PrEP, TRUVADA, TRUVADA for PrEP, GILEAD, and the GILEAD logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
© 2025 Gilead Sciences, Inc.