A Gilead Medical Affairs Website Information on Clinical Implementation of Lenacapavir for HIV-1 Pre-Exposure Prophylaxis (LEN for PrEP)

LEN for PrEP (marketed as YEZTUGO) is a human immunodeficiency virus type 1 (HIV-1) antiretroviral agent with long-acting properties indicated for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg (77 lb) who have a higher likelihood of HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating LEN for PrEP.

LEN for PrEP is administered in a two-step dosing regimen. It starts with a combination of subcutaneous injections and oral tablets, followed by continuous subcutaneous injections once every 6 months (26 weeks) ± 2 weeks.

The efficacy and safety of LEN for PrEP in reducing the risk of HIV-1 acquisition were evaluated in two randomized, double-blind, active-controlled, multinational trials: PURPOSE 1 and PURPOSE 2.¹

PURPOSE 1:
Study Design

• Phase 3, double-blind, active-controlled, multicenter, randomized study in sexually active cisgender adolescent girls and young women (including participants who may become pregnant) in South Africa and Uganda who had a high likelihood of acquiring HIV-1.^1,2
• Background HIV-1 (bHIV) incidence – i.e., the HIV incidence expected in the absence of PrEP (analogous to a placebo group) – was calculated in the screened population (N=8,094).²
• Participants were randomly assigned in a 2:2:1 ratio to receive either twice-yearly (every 6 months) LEN for PrEP (N=2,134), once-daily F/TAF (emtricitabine/tenofovir alafenamide) (N=2,136), or once-daily F/TDF (emtricitabine/tenofovir disoproxil fumarate) (N=1,068) along with corresponding oral tablet placebo or placebo injection.^1,2
• The use of F/TAF for HIV prevention in cisgender women is investigational. The safety and efficacy for this use have not been established.⁴

Baseline Characteristics

• The median age of participants was 21 years (range, 16‑26); 99.9% were Black.¹
• Baseline characteristics in the randomized participants were similar to the screened population.¹

Outcomes/Results

• The efficacy endpoint was the rate of incident HIV-1 acquisitions per 100 person-years (PY) in participants randomized to LEN for PrEP compared with the rate of incident HIV-1 acquisitions per 100 PY in participants randomized to F/TDF.¹
• At the final analysis, incident HIV-1 acquisitions were observed in 0 participants in the LEN for PrEP group vs. 16 participants in the F/TDF group.¹

Overall HIV-1 Incidence Outcomes in PURPOSE 1 at Final Analysis^1a

LEN for PrEP demonstrated superiority with a 100% reduction in the likelihood of incident HIV-1 acquisition over F/TDF¹

PURPOSE 2:
Study Design

• Phase 3, double-blind, active-controlled, multicenter, randomized trial in sexually active cisgender gay, bisexual, and other men, transgender women, transgender men, and gender nonbinary individuals who had unknown HIV-1 status at screening and who had a higher likelihood of acquiring HIV-1 based on sexual activity with male partners.^1,3
• Background HIV-1 incidence was calculated in the screened population (N=4,634).³
• Participants were randomized to receive twice-yearly (every 6 months) LEN for PrEP (N=2,179) or once-daily F/TDF (N=1,086) in a 2:1 ratio.¹

Baseline Characteristics

• The median age of participants was 29 years (range, 17-74); 67% were non-White; 63% were Hispanic/Latine; and 22% identified as gender-diverse (transgender women, transgender men, and gender nonbinary people).^1,3
• Baseline characteristics in the randomized participants were similar to the screened population.¹

Outcomes/Results

• The efficacy endpoint was the rate of incident HIV-1 acquisitions per 100 PY in participants randomized to LEN for PrEP compared with the rate of incident HIV-1 acquisitions per 100 PY in participants randomized to F/TDF.¹
• At the final analysis, incident HIV-1 acquisitions were observed in 2 participants in the LEN for PrEP group vs. 9 participants in the F/TDF group.¹

Overall HIV-1 Incidence Outcomes in PURPOSE 2 at Final Analysis^1a

LEN for PrEP demonstrated superiority with an 89% reduction in the likelihood of incident HIV-1 acquisition over F/TDF¹

LEN for PrEP Safety Data¹

• Adverse drug reactions (all grades) reported in ≥2% of participants receiving LEN for PrEP in either PURPOSE 1 or PURPOSE 2 were injection site reactions (ISRs), headache, nausea, dizziness, vomiting, and diarrhea.
• ISRs (all grades) reported in ≥2% of participants receiving LEN for PrEP in PURPOSE 1 or PURPOSE 2 included nodule, pain, induration, swelling, pruritis, erythema, bruising, and warmth.
• The majority of ISRs associated with LEN for PrEP in PURPOSE 1 and PURPOSE 2 were mild or moderate in severity.
• Injection site nodule was the most commonly reported ISR in individuals receiving LEN for PrEP in PURPOSE 1 and PURPOSE 2 and resolved more slowly than other ISRs.
• In PURPOSE 1, injection site nodule was reported in 64% of participants who received LEN for PrEP. The median duration of nodules associated with the first injections of LEN for PrEP was 350 (interquartile range: 182, 470) days. The median of the maximum observed nodule diameter from each participant was 3.0 (interquartile range: 2.0, 3.5) cm.
• In PURPOSE 2, injection site nodule was reported in 63% of participants who received LEN for PrEP. The median duration of nodules associated with the first injections of LEN for PrEP was 297 (interquartile range: 176, 423) days. The median of the maximum observed nodule diameter for each participant was 3.0 (interquartile range: 2.0, 4.0) cm.

Grade 3 ISRs reported in PURPOSE 1 included:²

• 6 cases of injection-site ulcer (3 in the LEN for PrEP group, 2 in the F/TAF group, and 1 in the F/TDF group)
• 1 case of nodule (in the LEN for PrEP group)
• 1 case of pain (in the F/TDF group)

Grade 3 ISRs reported in PURPOSE 2 included:³

• 7 cases of ulcer in the LEN for PrEP group
• 5 cases of pain (4 in the LEN for PrEP group, 1 in the F/TDF group)
• 3 cases of erythema in the LEN for PrEP group

Most Common Non-ISR Adverse Drug Reactions (ADRs)
Reported in ≥2% of Participants Receiving LEN for PrEP in PURPOSE 1 or PURPOSE 2:¹

a Participants received placebo subcutaneous injections (polyethylene glycol 400).

HIV-1=human immunodeficiency virus type 1; LEN for PrEP=lenacapavir for pre-exposure prophylaxis.

Indications and Usage
LEN for PrEP is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who have a higher likelihood of HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating LEN for PrEP.

HIV-1 Screening
Screen all individuals for HIV-1 prior to initiating LEN for PrEP, prior to each subsequent injection of LEN for PrEP, and additionally as clinically appropriate, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. When screening for HIV-1 prior to initiating LEN for PrEP, if an antigen/antibody-specific test is used and provides negative results, then such negative results should be confirmed using an RNA-specific assay, even if the results of the RNA-assay are available after LEN for PrEP initiation. When screening for HIV-1 prior to continuing LEN for PrEP, negative results from a rapid, point-of-care antigen/antibody test should be confirmed using a more sensitive assay.

General considerations when prescribing LEN for PrEP:*

• Adherence to scheduled dosing visits is important. Prior to starting LEN for PrEP, healthcare providers should carefully select individuals who agree to the required testing and an every-6-month injection dosing schedule. Individuals should be counseled about the importance of adherence to scheduled LEN for PrEP dosing visits to help reduce the likelihood of acquiring HIV-1 and development of resistance.
• LEN for PrEP should be used as part of a comprehensive prevention strategy to reduce the likelihood of acquiring HIV-1 and other sexually transmitted infections (STIs). This includes adherence to the administration schedule and engaging in safer sex practices (including using condoms).
• LEN for PrEP is not always effective in preventing HIV-1 acquisition. The time from initiation of LEN for PrEP to maximal protection against HIV-1 acquisition is unknown.
• Likelihood of HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including, but not limited to, condomless sex, past or current STIs, self-identified likelihood of HIV acquisition, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high-prevalence area or network.
• Counsel individuals on the use of other prevention measures (e.g., consistent and correct condom use; knowledge of partner(s)’ HIV-1 status, including viral suppression status; and regular testing for STIs that can facilitate HIV-1 transmission). Inform individuals about and support their efforts in reducing sexual behaviors associated with the increased likelihood of HIV-1 acquisition.

Considerations for specific populations
Pregnancy

• Data from PURPOSE 1 with LEN for PrEP use during pregnancy have not identified a drug-associated risk for miscarriage, or adverse maternal or fetal outcomes when compared to active control.
• The rate of major birth defects in LEN for PrEP-exposed pregnancies did not exceed the background prevalence rates.
• Risk estimates are imprecise due to small numbers of exposed pregnancies.
• Published studies indicate an increased likelihood of acquiring HIV during pregnancy and an increased likelihood of mother-to-child transmission during acute HIV cases. In women who are likely to acquire HIV-1, consideration should be given to methods to prevent acquisition of HIV-1, including continuing or initiating LEN for PrEP, during pregnancy.
• There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to LEN for PrEP during pregnancy. Healthcare providers are encouraged to register individuals by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.

Lactation

• Lenacapavir is present in human milk.
• Lenacapavir was detected at very low levels in infants who were breastfed by individuals who became pregnant while receiving LEN for PrEP.
• No adverse effects of lenacapavir in breastfed infants have been observed.
• It is not known if LEN for PrEP affects milk production.
• In women without HIV-1, the developmental and health benefits of breastfeeding and the mother’s clinical need for LEN for PrEP should be considered along with any potential adverse effects on the breastfed child from LEN for PrEP and the likelihood of HIV-1 acquisition due to nonadherence and subsequent mother-to-child transmission.

Pediatrics

• The safety and efficacy of LEN for PrEP have been established in adolescent individuals weighing at least 35 kg who have an increased likelihood of HIV-1 acquisition.
• PURPOSE 1 and PURPOSE 2 enrolled a total of 128 adolescent participants. In the 59 adolescents who received LEN for PrEP, the safety data were comparable to the safety data reported in adults receiving LEN for PrEP.
• Adolescents may benefit from additional counseling and appointment reminders to support adherence to the dosing and testing schedule.
• The safety, effectiveness, and pharmacokinetics of LEN for PrEP in pediatric populations weighing less than 35 kg have not been established.

Geriatrics

• Clinical studies of LEN for PrEP did not include sufficient numbers of participants aged 65 and over to determine whether they respond differently from younger individuals.
• In general, caution should be exercised in the administration of LEN for PrEP in elderly individuals, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Renal impairment

• No dosage adjustment of LEN for PrEP is recommended in individuals with mild, moderate, or severe renal impairment (estimated creatinine clearance ≥15 mL per minute).
• LEN for PrEP has not been studied in individuals with ESRD (estimated creatinine clearance < 15mL per minute).

Hepatic impairment

• No dosage adjustment of LEN for PrEP is recommended in individuals with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment.
• LEN for PrEP has not been studied in individuals with severe hepatic impairment (Child-Pugh Class C).

LEN for PrEP is supplied as a combination of oral tablets and subcutaneous injections.

YEZTUGO tablets
(NDC 61958-3401-1)
(Each tablet contains 300 mg of lenacapavir)

Images not to actual size.

Each bottle contains 4 tablets:

• Beige-colored
• Capsule-shaped
• Film-coated
• Debossed with ‘GSI’ on one side and ‘62L’ on the other side

YEZTUGO injection
(NDC 61958-3402-1)
(Each single-dose vial contains 463.5 mg/1.5 mL of lenacapavir)

Each injection dosing kit contains all the necessary components for injecting one complete dose (two 1.5 mL injections) of YEZTUGO:

• 2 single-dose clear glass vials containing:
  • Clear, yellow solution with no visible particles
  • Sterile
  • Preservative-free
• 2 disposable syringes
• 2 withdrawal needles (18-gauge, 1.5-inch)
• 2 injection safety needles for subcutaneous injection (22-gauge, 0.5-inch)

Effect of Other Drugs on LEN for PrEP
Lenacapavir is a substrate of P-gp, UGT1A1, and CYP3A.

Effect of LEN for PrEP on Other Drugs

• Lenacapavir is a moderate inhibitor of CYP3A and a P-gp inhibitor.
  • The co-administration of LEN for PrEP with sensitive substrates of CYP3A or P-gp may increase the concentrations of these substrates and result in the increased likelihood of their adverse events. See the prescribing information of these sensitive substrates for dosing recommendations or appropriate monitoring of safety.
  • Due to the long half-life of lenacapavir following subcutaneous administration, LEN for PrEP may increase the exposure of drugs primarily metabolized by CYP3A initiated within 9 months after the last subcutaneous dose of LEN for PrEP.

Drugs without Clinically Significant Interactions with LEN for PrEP
Based on drug interaction studies conducted with LEN for PrEP, no clinically significant drug interactions have been observed, with:

• atorvastatin
• famotidine
• pitavastatin
• rosuvastatin
• tenofovir alafenamide
• voriconazole

• Providing PrEP medication for individuals who need or want PrEP promptly is crucial to reducing the likelihood of acquiring HIV.¹
• If LEN for PrEP is recommended and immediately available, same-day initiation is possible; however, individuals must have a negative HIV-1 test prior to initiation.* If not, consider starting or continuing another FDA-approved PrEP medication until LEN for PrEP becomes available.^1,2
• The decision to start PrEP should be based on healthcare professional judgment after shared clinical decision-making and based on individual interest.¹
• If the decision has been made to switch individuals who need or want PrEP from agents with activity against HBV (such as F/TDF or F/TAF) to LEN for PrEP, healthcare professionals should be aware that discontinuation of these agents can cause severe hepatitis B exacerbation in individuals living with HBV. Monitor liver function closely and consider HBV therapy if needed for these individuals.^3,4

Algorithm intended for illustrative purposes only. This information does not constitute medical advice.

The decision to start PrEP should be based on healthcare professional judgment after shared clinical decision-making and based on individual interest.

The LEN for PrEP dosing schedule consists of a required initiation dosing (subcutaneous injections and oral tablets) followed by once-every-6-months (26 weeks) ± 2 weeks continuation dosing (subcutaneous injections).¹

Subcutaneous (SC) injections are administered into the abdomen by a healthcare provider. The thigh may be used as an alternate site if preferred. Do NOT administer intradermally due to the risk of serious injection site reactions.¹

An oral initiation dose is needed on Day 1 and Day 2 to achieve adequate concentrations of lenacapavir quickly due to the slow initial release of subcutaneous lenacapavir.^1,2

Dosing Schedule for LEN for PrEP Initiation and Continuation in Adults and Adolescents Weighing at Least 35 kg¹

Initiation^a

Day 1

927 mg by subcutaneous injection
(2 x 1.5 mL injections) and
600 mg orally (2 x 300 mg tablets)

Day 2

600 mg orally
(2 x 300 mg tablets)

Continuation

Every 6 months (26 weeks)^b +/- 2 weeks

927 mg by subcutaneous injection
(2 x 1.5 mL injections)

Missed Doses¹

Missed Oral Initiation Dose

• If the Day 2 oral initiation dose (600 mg) is missed, it should be taken as soon as possible.
• Day 1 and Day 2 oral initiation doses should not be taken on the same day.

Anticipated Delayed Injections¹

• During continuation dosing, if a scheduled 6-month injection is anticipated to be delayed by more than 2 weeks, LEN for PrEP tablets may be taken on an interim basis (for up to 6 months if needed), until injections resume.

Dosing Schedule for Anticipated Delayed Injections: Weekly Oral Dosage¹

a Use on an interim basis only (for up to 6 months if needed).

Missed Injections¹

• Individuals who miss a scheduled injection visit should be clinically reassessed to ensure resumption of LEN for PrEP remains appropriate, and that the individual remains HIV-1 negative.
• During continuation dosing, if more than 28 weeks have elapsed since the last injection and LEN for PrEP tablets have not been taken, please follow the below dosing schedule after unplanned missed injections.
• Adherence to the injection dosing schedule is strongly recommended.

Dosing Schedule After Missed Injections¹

Dosing Recommendations for Individuals Receiving LEN for PrEP and Initiating a STRONG or MODERATE CYP3A Inducer^1a

Proceed with scheduled continuation injection dosing of LEN for PrEP

927 mg by subcutaneous injection
(2 x 1.5 mL injections) every 26 weeks (+/- 2 weeks)

Administer SUPPLEMENTAL DOSES of LEN for PrEP as follows:

Wait at least 2 days after LEN for PrEP initiation before initiating STRONG CYP3A inducers. MODERATE CYP3A inducers may be started at any time after LEN for PrEP initiation.

a Dosing recommendations are not available for the initiation of LEN for PrEP in individuals already receiving strong or moderate CYP3A inducers, nor in individuals receiving the weekly oral dosage of LEN for PrEP (see Dosing Schedule after Anticipated Delayed Injections: Weekly Oral Dosage)

Example Scenario: Jamie receives LEN for PrEP and then starts a STRONG CYP3A inducer

NOTE: The STRONG CYP3A inducer may be initiated any time after 2 days following LEN for PrEP initiation.

 

• On January 1^st, Jamie initiates LEN for PrEP.
  • Day 1: 2 x 1.5 mL SC injections, 2 x 300 mg oral tablets
  • Day 2: 2 x 300 mg oral tablets

• Jamie’s next continuation dose of LEN for PrEP is scheduled 26 weeks later, on July 1^st.
  • 2 x 1.5 mL SC injections

• On March 5^th of the same year, Jamie begins a STRONG CYP3A inducer.
  • A supplemental LEN for PrEP dose is provided on March 5^th and March 6^th (on the same day and the day after starting the STRONG CYP3A inducer).
    • March 5: 2 x 1.5 mL SC injections, 2 x 300 mg oral tablets
    • March 6: 2 x 300 mg oral tablets

• Jamie continues to receive scheduled LEN for PrEP continuation doses every 26 weeks (+/- 2 weeks): January and July.
  • 2 x 1.5 mL SC injections

• As long as Jamie continues to take the STRONG CYP3A inducer for >6 months, Jamie should also continue to receive supplemental LEN for PrEP doses every 26 weeks (+/- 2 weeks) from the original supplemental dose: September.
  • September 5: 2 x 1.5 mL SC injections, 2 x 300 mg oral tablets
  • September 6: 2 x 300 mg oral tablets

• Jamie stops their STRONG CYP3A inducer on October 15^th. After STOPPING the STRONG CYP3A inducer, Jamie resumes scheduled continuation injections dosing of LEN for PrEP. No additional supplemental doses are required.
  • 2 x 1.5 mL SC injections every 26 weeks (+/- 2 weeks)

Dosing recommendations are not available for the initiation of LEN for PrEP in individuals already receiving STRONG CYP3A inducers.

Example Scenario: Ari receives LEN for PrEP and then starts a MODERATE CYP3A inducer

NOTE: The MODERATE CYP3A inducer may be initiated any time after LEN for PrEP is initiated.

 

• On January 1^st, Ari initiates LEN for PrEP.
  • Day 1: 2 x 1.5 mL SC injections, 2 x 300 mg oral tablets
  • Day 2: 2 x 300 mg oral tablets

• Ari’s next continuation dose of LEN for PrEP is scheduled 26 weeks later, on July 1^st.
  • 2 x 1.5 mL SC injections

• On March 5^th of the same year, Ari begins MODERATE CYP3A inducer.
  • A supplemental LEN for PrEP dose is provided on March 5^th (on the same day as starting a MODERATE CYP3A inducer).
    • March 5: 1 x 1.5 mL SC injection

• Ari continues to receive scheduled LEN for PrEP continuation doses every 26 weeks (+/- 2 weeks): January and July.
  • 2 x 1.5 mL SC injections

• As long as Ari continues to take the MODERATE CYP3A inducer >6 months, Ari should also continue to receive supplemental LEN for PrEP doses every 26 weeks (+/- 2 weeks) from the original supplemental dose: September.
  • September 5: 1 x 1.5 mL SC injection

• Ari stops their MODERATE CYP3A inducer on October 15^th. After STOPPING the MODERATE CYP3A inducer, Ari resumes scheduled continuation injection dosing of LEN for PrEP. No additional supplemental doses are required.
  • 2 x 1.5 mL SC injections every 26 weeks (+/- 2 weeks)

Dosing recommendations are not available for the initiation of LEN for PrEP in individuals already receiving MODERATE CYP3A inducers.

YEZTUGO Injection Kit¹

YEZTUGO injection is supplied in a single-use dosing kit (NDC 61958-3402-1), containing all the necessary components for two 1.5 mL injections (one complete dose), including withdrawal and injection needles.

YEZTUGO Injection Kit Components

Two vials of 1.5 mL
LEN for PrEP

Two syringes for injecting LEN for PrEP

Two 18G, 1.5-inch needles with a pink hub for withdrawing LEN for PrEP from the vials

Two 22G, 0.5-inch needles for injecting LEN for PrEP

Prior to injection, ensure that:

• Vial and prepared syringe contain a yellow solution with no particles. Do not use if the solution is discolored or if it contains particulate matter.
• Contents are not damaged.
• Product is not expired.
• Aseptic technique is used.
• Once the solution is withdrawn from the vials, the subcutaneous injections should be administered as soon as possible.

LEN for PrEP Administration¹

• Administer LEN for PrEP tablets orally, with or without food.
• Administer LEN for PrEP injections subcutaneously (SC). LEN for PrEP injection is only for SC administration into the abdomen by a healthcare provider. The thigh may be used as an alternate site if preferred. Do NOT administer intradermally due to risk of serious injection site reactions.
• A subcutaneous drug depot forms following LEN for PrEP injection. In some individuals, this may lead to a nodule at the injection site.

LEN for PrEP Injection Steps for Withdrawal Needle Injection Kit:¹

1

Prepare vial

• Remove cap from the vial.
• Clean vial stopper with alcohol wipe.

2

Prepare withdrawal needle

• Attach 18G withdrawal needle to syringe by the pink hub.

3

Fill syringe

• Insert the withdrawal needle into the rubber stopper of vial.
• Inject 1.5 mL of air into the vial.
• Fill the syringe by withdrawing all contents.

4

Remove 18G withdrawal needle from syringe

• Remove withdrawal needle by pulling the pink hub away from the syringe.

5

Prepare injection needle

• Attach 22G injection needle to syringe.
• Expel air bubbles.
• Prime the needle to 1.5 mL.

6

Select and clean an injection site

• Select an injection site and clean it.
• Injection site should be at least 2 inches from navel if injecting into the abdomen.
• The thigh may be used as alternate site if preferred.

7

Inject 1.5 mL of LEN for PrEP subcutaneously

• Gently pinch a broad portion of skin at the injection site to help fully insert the needle into the SC layer where the drug depot forms.
• Fully insert the needle at a 90^o-angle (preferred for SC injection) or at a 45^o-angle (which is acceptable).

8

Administer
2nd injection

• Repeat Steps 1 through 7 for second injection.
• Choose a second injection site at least 4 inches from the first injection site and 2 inches from the navel.

To help ensure correct administration technique, here are some key points to consider:

• Ensure team members are fully trained on how to administer LEN for PrEP per full U.S. Prescribing Information.
• Team members should be prepared to answer questions about the injection process and educate on potential adverse events, such as injection site reactions, as outlined in the “Patient Counseling Information” section of the full U.S. Prescribing Information.
• Counsel and support individuals on:
  • adhering to the required initiation and continuation dosing schedule,
  • the use of other measures to reduce the likelihood of STIs, and
  • testing for HIV-1 and other STIs.
• Some individuals, such as adolescents, may benefit from additional counseling and appointment reminders to support adherence.

The most common adverse drug reactions (all grades) reported in at least 5% of participants receiving LEN for PrEP in either PURPOSE 1 or PURPOSE 2 were ISRs, headache, and nausea.

Adverse Drug Reactions (ADRs) Reported in ≥2%a of Participants Receiving LEN for PrEP in PURPOSE 1 or PURPOSE 2

ISRs (all grades) reported in ≥2% of participants receiving LEN for PrEP in PURPOSE 1 or PURPOSE 2 included nodule, pain, induration, swelling, pruritis, erythema, bruising, and warmth.

The majority of ISRs associated with LEN for PrEP in PURPOSE 1 and PURPOSE 2 were mild or moderate in severity.

Injection-Associated Adverse Drug Reactions

PURPOSE 1:

• Grade 3 ISRs were reported in 4 (0.2%) participants and included ulcer and nodule.
• LEN for PrEP was discontinued due to ISRs in 4 (0.2%) participants.
• None of the ISRs were serious.

Nodules

• Injection site nodule was reported in 64% of participants who received LEN for PrEP and resolved more slowly than other ISRs.
• The median duration of nodules associated with the first injections of LEN for PrEP was 350 (interquartile range: 182, 470) days.
• The median of the maximum observed nodule diameter from each participant was 3.0 (interquartile range: 2.0, 3.5) cm.
• Prior to receiving LEN for PrEP, individuals should be made aware that this is a common side effect.

Other ISRs

• Other ISRs reported in more than 2% of participants who received LEN for PrEP were pain (31%), swelling (4%), induration (4%), and pruritus (2%).

PURPOSE 2:

• Grade 3 ISRs were reported in 14 (0.6%) participants and included ulcer, pain, erythema, edema, and dermatitis.
• LEN for PrEP was discontinued due to ISRs in 26 (1.2%) participants.
• None of the ISRs were serious.

Nodules

• Injection site nodule was reported in 63% of participants who received LEN for PrEP and resolved more slowly than other ISRs.
• The median duration of nodules associated with the first injections of LEN for PrEP was 297 (interquartile range: 176, 423) days.
• The median of the maximum observed nodule diameter for each participant was 3.0 (interquartile range: 2.0, 4.0) cm.

Other ISRs

• Other ISRs reported in more than 2% of participants who received LEN for PrEP were pain (56%), erythema (17%), induration (16%), swelling (7%), bruising (3%), pruritus (3%), and warmth (2%).

To report SUSPECTED ADVERSE DRUG REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

LEN for PrEP adherence and persistence are crucial for achieving optimal outcomes.¹

• Adherence is defined as how closely an individual follows the dosing regimen recommended by their healthcare providers.²
  • Across PrEP clinical trials, level of adherence correlates to the efficacy of PrEP medication.²
• Persistence is defined as duration of ongoing use.²
  • During periods where the likelihood of HIV acquisition peaks, persistent PrEP use is crucial to help reduce the likelihood of HIV acquisition.²
• Counsel individuals about the importance of adherence to scheduled LEN for PrEP dosing visits.¹