DESCOVY (Page 8 of 9)

14.3 Clinical Trial Results for HIV-1 PrEP

The efficacy and safety of DESCOVY to reduce the risk of acquiring HIV-1 infection were evaluated in a randomized, double-blind multinational trial (DISCOVER) in HIV-seronegative men (N=5,262) or transgender women (N=73) who have sex with men and are at risk of HIV-1 infection, comparing once daily DESCOVY (N=2,670) to TRUVADA (FTC/TDF 200 mg/300 mg; N=2,665). Evidence of risk behavior at entry into the trial included at least one of the following: two or more unique condomless anal sex partners in the past 12 weeks or a diagnosis of rectal gonorrhea/chlamydia or syphilis in the past 24 weeks. The median age of participants was 34 years (range, 18-76); 84% were White, 9% Black/Mixed Black, 4% Asian, and 24% Hispanic/Latino. At baseline, 897 participants (17%) reported receiving TRUVADA for PrEP.

At weeks 4, 12, and every 12 weeks thereafter, all participants received local standard of care HIV-1 prevention services, including HIV-1 testing, evaluation of adherence, safety evaluations, risk-reduction counseling, condoms, management of sexually transmitted infections, and assessment of sexual behavior.

Trial participants maintained a high risk of sexual HIV-1 acquisition, with high rates of rectal gonorrhea (DESCOVY, 24%; TRUVADA, 25%), rectal chlamydia (DESCOVY, 30%; TRUVADA, 31%), and syphilis (14% in both treatment groups) during the trial.

The primary outcome was the incidence of documented HIV-1 infection per 100 person-years in participants randomized to DESCOVY and TRUVADA (with a minimum follow-up of 48 weeks and at least 50% of participants having 96 weeks of follow-up). DESCOVY was non-inferior to TRUVADA in reducing the risk of acquiring HIV-1 infection (Table 16). The results were similar across the subgroups of age, race, gender identity, and baseline TRUVADA for PrEP use.

Table 16 HIV-1 Infection Results in DISCOVER Trial – Full Analysis Set

	DESCOVY(N=2,670)	TRUVADA(N=2,665)	Rate Ratio(95% CI)
	4,370 person-years	4,386 person-years
CI = Confidence interval.
HIV-1 infections, n	7	15
Rate of HIV-1 infections per 100 person-years	0.16	0.34	0.468(0.19, 1.15)

Of the 22 participants diagnosed with HIV-1 infection in the trial, five had suspected baseline infection prior to study entry (DESCOVY, 1; TRUVADA, 4). In a case-control substudy of intracellular drug levels and estimated number of daily doses as measured by dried blood spot testing, median intracellular tenofovir diphosphate concentrations were substantially lower in participants infected with HIV-1 at the time of diagnosis compared with uninfected matched control participants. For both DESCOVY and TRUVADA, efficacy was therefore strongly correlated to adherence to daily dosing.

16 HOW SUPPLIED/STORAGE AND HANDLING

DESCOVY tablets are available in bottles and blister packs containing 30 tablets:

Bottles

• 200 mg/25 mg tablets each contain 200 mg of emtricitabine (FTC) and 25 mg of tenofovir alafenamide (TAF). These tablets are blue, rectangular-shaped, and film-coated with “GSI” debossed on one side and “225” on the other side (NDC 61958-2002-1).
• 120 mg/15 mg tablets each contain 120 mg of FTC and 15 mg of TAF. These tablets are white, round-shaped, and film coated with “GSI” debossed on one side and “15” on the other side (NDC 61958-2005-1).

Bottles contain a silica gel desiccant, polyester coil, and child resistant closure.

Keep bottle tightly closed.

Blister Pack

• 200 mg/25 mg tablets each contain 200 mg of FTC and 25 mg of TAF. These tablets are blue, rectangular-shaped, and film-coated with “GSI” debossed on one side and “225” on the other side (NDC 61958-2002-2).

Blister packs are sealed with a child-resistant laminated foil lidding material (peel-push) and each blister cavity contains a die-cut desiccant film which is heat staked to the foil lidding material.

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) (see USP Controlled Room Temperature).

Dispense only in original container.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Important Information for Uninfected Individuals Taking DESCOVY for HIV-1 PrEP

Advise HIV-1 uninfected individuals about the following [see Warnings and Precautions (5.2)]:

• The need to confirm that they are HIV-negative before starting to take DESCOVY to reduce the risk of acquiring HIV-1.
• That HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking DESCOVY, because DESCOVY alone does not constitute a complete regimen for HIV-1 treatment.
• The importance of taking DESCOVY on a regular dosing schedule and strict adherence to the recommended dosing schedule to reduce the risk of acquiring HIV-1. Uninfected individuals who miss doses are at greater risk of acquiring HIV-1 than those who do not miss doses.
• That DESCOVY does not prevent other sexually acquired infections and should be used as part of a complete prevention strategy including other prevention measures.
• To use condoms consistently and correctly to lower the chances of sexual contact with any body fluids such as semen, vaginal secretions, or blood.
• The importance of knowing their HIV-1 status and the HIV-1 status of their partner(s).
• The importance of virologic suppression in their partner(s) with HIV-1.
• The need to get tested regularly for HIV-1 (at least every 3 months, or more frequently for some individuals such as adolescents) and to ask their partner(s) to get tested as well.
• To report any symptoms of acute HIV-1 infection (flu-like symptoms) to their healthcare provider immediately.
• That the signs and symptoms of acute infection include fever, headache, fatigue, arthralgia, vomiting, myalgia, diarrhea, pharyngitis, rash, night sweats, and adenopathy (cervical and inguinal).
• To get tested for other sexually transmitted infections, such as syphilis, chlamydia, and gonorrhea, that may facilitate HIV-1 transmission.
• To assess their sexual risk behavior and get support to help reduce sexual risk behavior.

Post-treatment Acute Exacerbation of Hepatitis B in Patients with HBV Infection

Inform individuals that severe acute exacerbations of hepatitis B have been reported in patients who are infected with HBV and have discontinued products containing FTC and/or TDF and may likewise occur with discontinuation of DESCOVY [see Warnings and Precautions (5.1)]. Advise HBV-infected individuals to not discontinue DESCOVY without first informing their healthcare provider.

Immune Reconstitution Syndrome

Advise HIV-1 infected patients to inform their healthcare provider immediately of any symptoms of infection. In some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started [see Warnings and Precautions (5.3)].

New Onset or Worsening Renal Impairment

Advise HIV-1 infected patients and uninfected individuals to avoid taking DESCOVY with concurrent or recent use of nephrotoxic agents. Postmarketing cases of renal impairment, including acute renal failure, have been reported [see Warnings and Precautions (5.4)].

Lactic Acidosis and Severe Hepatomegaly

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with use of drugs similar to DESCOVY. Advise HIV-1 infected patients and uninfected individuals that they should stop DESCOVY if they develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity [see Warnings and Precautions (5.5)].

Dosage Recommendations for Treatment of HIV-1 Infection

Inform HIV-1 infected patients that it is important to take DESCOVY with other antiretroviral drugs for the treatment of HIV-1 on a regular dosing schedule with or without food and to avoid missing doses as it can result in development of resistance [see Dosage and Administration (2.3, 2.4)].

Pregnancy Registry

Inform individuals using DESCOVY that there is an antiretroviral pregnancy registry to monitor fetal outcomes of pregnant women exposed to DESCOVY [see Use in Specific Populations (8.1)].

Lactation

Instruct mothers with HIV-1 infection not to breastfeed because of the risk of passing the HIV-1 virus to the baby [see Use in Specific Populations (8.2)].

DESCOVY and TRUVADA are trademarks of Gilead Sciences, Inc., or its related companies. All other trademarks referenced herein are the property of their respective owners.

© 2022 Gilead Sciences, Inc. All rights reserved.

This Medication Guide has been approved by the U.S. Food and Drug Administration				Revised: 01/2022
Medication GuideDESCOVY® (des-KOH-vee)(emtricitabine and tenofovir alafenamide)tablets
Read this Medication Guide before you start taking DESCOVY and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. This Medication Guide provides information about two different ways that DESCOVY may be used. See the section “What is DESCOVY?“ for detailed information about how DESCOVY may be used.
What is the most important information I should know about DESCOVY?DESCOVY can cause serious side effects, including: Worsening of hepatitis B virus (HBV) infection. Your healthcare provider will test you for HBV infection before or when you start treatment with DESCOVY. If you have HBV infection and take DESCOVY, your HBV may get worse (flare-up) if you stop taking DESCOVY. A “flare-up” is when your HBV infection suddenly returns in a worse way than before. Do not run out of DESCOVY. Refill your prescription or talk to your healthcare provider before your DESCOVY is all gone. Do not stop taking DESCOVY without first talking to your healthcare provider. If you stop taking DESCOVY, your healthcare provider will need to check your health often and do blood tests regularly for several months to check your liver, and may give you a medicine to treat hepatitis B. Tell your healthcare provider about any new or unusual symptoms you may have after you stop taking DESCOVY. For more information about side effects, see the section “What are the possible side effects of DESCOVY?“Other important information for people who take DESCOVY to help reduce their risk of getting human immunodeficiency virus-1 (HIV-1) infection, also called pre-exposure prophylaxis or “PrEP”: Before taking DESCOVY to reduce your risk of getting HIV-1: You must be HIV-1 negative to start DESCOVY. You must get tested to make sure that you do not already have HIV-1 infection. Do not take DESCOVY for HIV-1 PrEP unless you are confirmed to be HIV-1 negative. Some HIV-1 tests can miss HIV-1 infection in a person who has recently become infected. If you have flu-like symptoms, you could have recently become infected with HIV-1. Tell your healthcare provider if you had a flu-like illness within the last month before starting DESCOVY or at any time while taking DESCOVY. Symptoms of new HIV-1 infection include:
	tiredness fever joint or muscle aches headache sore throat		vomiting or diarrhea rash night sweats enlarged lymph nodes in the neck or groin
While you are taking DESCOVY for HIV-1 PrEP: DESCOVY does not prevent other sexually transmitted infections (STIs). Practice safer sex by using a latex or polyurethane condom to reduce the risk of getting STIs. You must stay HIV-1 negative to keep taking DESCOVY for HIV-1 PrEP. Know your HIV-1 status and the HIV-1 status of your partners. Ask your partners with HIV-1 if they are taking HIV-1 medicines and have an undetectable viral load. An undetectable viral load is when the amount of virus in the blood is too low to be measured in a lab test. To maintain an undetectable viral load, your partners must keep taking HIV-1 medicines every day. Your risk of getting HIV-1 is lower if your partners with HIV-1 are taking effective treatment. Get tested for HIV-1 at least every 3 months or when your healthcare provider tells you. Get tested for other STIs such as syphilis, chlamydia, and gonorrhea. These infections make it easier for HIV-1 to infect you. If you think you were exposed to HIV-1, tell your healthcare provider right away. They may want to do more tests to be sure you are still HIV-1 negative. Get information and support to help reduce sexual risk behaviors. Do not miss any doses of DESCOVY. Missing doses increases your risk of getting HIV-1 infection. If you do become HIV-1 positive, you need more medicine than DESCOVY alone to treat HIV-1. DESCOVY by itself is not a complete treatment for HIV-1. If you have HIV-1 and take only DESCOVY, over time your HIV-1 may become harder to treat.
What is DESCOVY?DESCOVY is a prescription medicine that may be used in two different ways. DESCOVY is used: to treat HIV-1 infection in adults and children who weigh at least 77 pounds (35 kg) together with other HIV-1 medicines in children who weigh at least 31 pounds (14 kg) and less than 77 pounds (35 kg) together with certain other HIV-1 medicines. Your healthcare provider will determine which other HIV-1 medicines may be used with DESCOVY. for HIV-1 PrEP to reduce the risk of getting HIV-1 infection in adults and adolescents who weigh at least 77 pounds (35 kg). It is not known if DESCOVY is effective in reducing the risk of getting HIV-1 from certain types of sex. DESCOVY for PrEP is not for use in people born female (assigned female at birth) who are at risk of getting HIV-1 infection from vaginal sex, because its effectiveness has not been studied. HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS). DESCOVY contains the prescription medicines emtricitabine and tenofovir alafenamide.It is not known if DESCOVY for treatment of HIV-1 infection is safe and effective in children who weigh less than 31 pounds (14 kg).It is not known if DESCOVY is safe and effective in reducing the risk of HIV-1 infection in people who weigh less than 77 pounds (35 kg).
For people taking DESCOVY for HIV-1 PrEP:Do not take DESCOVY for HIV-1 PrEP if: you already have HIV-1 infection. If you are HIV-1 positive, you need to take other medicines with DESCOVY to treat HIV-1. DESCOVY by itself is not a complete treatment for HIV-1. you do not know your HIV-1 infection status. You may already be HIV-1 positive. You need to take other HIV-1 medicines with DESCOVY to treat HIV-1 infection. DESCOVY can only help reduce your risk of getting HIV-1 infection before you are infected.
What should I tell my healthcare provider before taking DESCOVY?Before taking DESCOVY, tell your healthcare provider about all of your medical conditions, including if you: have liver problems, including HBV infection have kidney problems are pregnant or plan to become pregnant. It is not known if DESCOVY can harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with DESCOVY.Pregnancy Registry: There is a pregnancy registry for people who take DESCOVY during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk with your healthcare provider about how you can take part in this registry. are breastfeeding or plan to breastfeed. Do not breastfeed if you take DESCOVY for treatment of HIV-1 because of the risk of passing HIV-1 to your baby. One of the ingredients in DESCOVY (emtricitabine) passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may interact with DESCOVY. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine. You can ask your healthcare provider or pharmacist for a list of medicines that interact with DESCOVY. Do not start a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take DESCOVY with other medicines.
How should I take DESCOVY? Take DESCOVY exactly as your healthcare provider tells you to take it. If you take DESCOVY to treat HIV-1 infection, you need to take DESCOVY with other HIV-1 medicines. Your healthcare provider will tell you what medicines to take and how to take them. Take DESCOVY 1 time each day with or without food. If you are on dialysis, take your daily dose of DESCOVY following dialysis. Do not change your dose or stop taking DESCOVY without first talking with your healthcare provider. Stay under a healthcare provider’s care when taking DESCOVY. Do not miss a dose of DESCOVY. If you take too much DESCOVY, call your healthcare provider or go to the nearest hospital emergency room right away. When your DESCOVY supply starts to run low, get more from your healthcare provider or pharmacy. If you are taking DESCOVY for treatment of HIV-1, the amount of virus in your blood may increase if the medicine is stopped for even a short time. The virus may develop resistance to DESCOVY and become harder to treat. If you are taking DESCOVY for HIV-1 PrEP, missing doses increases your risk of getting HIV-1 infection.
What are the possible side effects of DESCOVY?DESCOVY may cause serious side effects, including: See “What is the most important information I should know about DESCOVY?“ Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking medicines to treat HIV-1 infection. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having any new symptoms after starting your HIV-1 medicine. New or worse kidney problems, including kidney failure. Your healthcare provider should do blood and urine tests to check your kidneys before you start and while taking DESCOVY. Your healthcare provider may tell you to stop taking DESCOVY if you develop new or worse kidney problems. Too much lactic acid in your blood (lactic acidosis). Too much lactic acid is a serious but rare medical emergency that can lead to death. Tell your healthcare provider right away if you get these symptoms: weakness or being more tired than usual, unusual muscle pain, being short of breath or fast breathing, stomach pain with nausea and vomiting, cold or blue hands and feet, feel dizzy or lightheaded, or a fast or abnormal heartbeat. Severe liver problems. In rare cases, severe liver problems can happen that can lead to death. Tell your healthcare provider right away if you get these symptoms: skin or the white part of your eyes turns yellow, dark “tea-colored” urine, light-colored stools, loss of appetite for several days or longer, nausea, or stomach-area pain. The most common side effect of DESCOVY for treatment of HIV-1 is nausea.The most common side effect of DESCOVY for HIV-1 PrEP is diarrhea.These are not all of the possible side effects of DESCOVY. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store DESCOVY? Store DESCOVY between 68°F to 77°F (20°C to 25°C). Keep DESCOVY in its original bottle or blister pack. Keep the bottle tightly closed. Keep DESCOVY and all medicines out of reach of children.
General information about the safe and effective use of DESCOVY. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use DESCOVY for a condition for which it was not prescribed. Do not give DESCOVY to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about DESCOVY that is written for health professionals.
What are the ingredients in DESCOVY?Active ingredients: emtricitabine and tenofovir alafenamide.Inactive ingredients: croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 200 mg/25 mg tablets are film-coated with a coating material containing indigo carmine aluminum lake, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. The 120 mg/15 mg tablets are film-coated with a coating material containing polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc. Manufactured and distributed by: Gilead Sciences, Inc. Foster City, CA 94404DESCOVY is a trademark of Gilead Sciences, Inc., or its related companies. All other trademarks referenced herein are the property of their respective owners.© 2022 Gilead Sciences, Inc. All rights reserved.208215-GS-009For more information, call 1-800-445-3235 or go to www.DESCOVY.com.