1.1 Treatment of HIV-1 Infection

DESCOVY is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg.

DESCOVY is indicated, in combination with other antiretroviral agents other than protease inhibitors that require a CYP3A inhibitor, for the treatment of HIV-1 infection in pediatric patients weighing at least 14 kg and less than 35 kg.

1.2 HIV-1 Pre-Exposure Prophylaxis (PrEP)

DESCOVY is indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (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 DESCOVY for HIV-1 PrEP [see Dosage and Administration (2.2) and Warnings and Precautions (5.2)].

2.1 Testing When Initiating and During Use of DESCOVY for Treatment of HIV-1 Infection or for HIV-1 PrEP

Prior to or when initiating DESCOVY, test individuals for hepatitis B virus infection [see Warnings and Precautions (5.1)].

Prior to or when initiating DESCOVY, and during use of DESCOVY on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all individuals. In individuals with chronic kidney disease, also assess serum phosphorus [see Warnings and Precautions (5.4)].

2.2 HIV-1 Screening for Individuals Receiving DESCOVY for HIV-1 PrEP

Screen all individuals for HIV-1 infection immediately prior to initiating DESCOVY for HIV-1 PrEP and at least once every 3 months while taking DESCOVY, and upon diagnosis of any other sexually transmitted infections (STIs) [see Indications and Usage (1.2), Contraindications (4), and Warnings and Precautions (5.2)].

If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, use a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection [see Warnings and Precautions (5.2), Use in Specific Populations (8.4), and Clinical Studies (14.3)].

2.3 Recommended Dosage for Treatment of HIV-1 Infection in Adults and Pediatric Patients Weighing at Least 35 kg

DESCOVY is a two-drug fixed dose combination product containing emtricitabine (FTC) and tenofovir alafenamide (TAF).

The recommended dosage of DESCOVY for treatment of HIV-1 is one tablet containing 200 mg FTC and 25 mg of TAF taken orally once daily with or without food in:

• adults and pediatric patients with body weight at least 35 kg and estimated creatinine clearance greater than or equal to 30 mL per minute; or
• adults with creatinine clearance below 15 mL per minute who are receiving chronic hemodialysis. On days of hemodialysis, administer the daily dose of DESCOVY after completion of hemodialysis treatment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

The safety and effectiveness of DESCOVY coadministered with an HIV-1 protease inhibitor that is administered with either ritonavir or cobicistat have not been established in adults with creatinine clearance below 15 mL per minute, with or without hemodialysis.

For specific dosing recommendations for coadministered antiretroviral drugs, refer to their respective prescribing information [see Drug Interactions (7)].

2.4 Recommended Dosage for Treatment of HIV-1 Infection in Pediatric Patients Weighing at Least 14 kg to Less than 35 kg

The recommended dosage of DESCOVY in pediatric patients weighing at least 14 kg to 35 kg is based on body weight and provided in Table 1. This dosing information is applicable to pediatric patients with estimated creatinine clearance greater than or equal to 30 mL per minute [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)] who are not receiving an HIV protease inhibitor that is administered with either ritonavir or cobicistat.

The safety and effectiveness of DESCOVY coadministered with an HIV-1 protease inhibitor that is administered with either ritonavir or cobicistat have not been established in pediatric subjects weighing less than 35 kg.

For specific dosing recommendations for coadministered antiretroviral drugs, refer to their respective prescribing information [see Drug Interactions (7)].

2.5 Recommended Dosage for HIV-1 PrEP in Adults and Adolescents Weighing at Least 35 kg

The dosage of DESCOVY for HIV-1 PrEP is one tablet (containing 200 mg of FTC and 25 mg of TAF) once daily taken orally with or without food in HIV-1 uninfected:

• adults and adolescents weighing at least 35 kg and with a creatinine clearance greater than or equal to 30 mL per minute; or
• adults with creatinine clearance below 15 mL per minute who are receiving chronic hemodialysis. On days of hemodialysis, administer the daily dose of DESCOVY after completion of hemodialysis treatment [see Indications and Usage (1.2) and Clinical Pharmacology (12.3)].

2.6 Not Recommended in Individuals with Severe Renal Impairment for Treatment of HIV-1 Infection or for HIV-1 PrEP

DESCOVY is not recommended in individuals with:

• severe renal impairment (estimated creatinine clearance of 15 to below 30 mL per minute); or
• end stage renal disease (ESRD; estimated creatinine clearance below 15 mL per minute) who are not receiving chronic hemodialysis [see Dosage and Administration (2.3, 2.5) and Use in Specific Populations (8.6)].

5.1 Severe Acute Exacerbation of Hepatitis B in Individuals with HBV Infection

All individuals should be tested for the presence of hepatitis B virus (HBV) before or when initiating DESCOVY [see Dosage and Administration (2.1)].

Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in HBV-infected individuals who have discontinued products containing FTC and/or tenofovir disoproxil fumarate (TDF) and may occur with discontinuation of DESCOVY. Individuals infected with HBV who discontinue DESCOVY should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, anti-hepatitis B therapy may be warranted, especially in individuals with advanced liver disease or cirrhosis, since post-treatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure. HBV-uninfected individuals should be offered vaccination.

5.2 Comprehensive Management to Reduce the Risk of Sexually Transmitted Infections, Including HIV-1, and Development of HIV-1 Resistance When DESCOVY Is Used for HIV-1 PrEP

Use DESCOVY for HIV-1 PrEP to reduce the risk of HIV-1 infection as part of a comprehensive prevention strategy, including adherence to daily administration and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). The time from initiation of DESCOVY for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown.

Risk for HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including but not limited to condomless sex, past or current STIs, self-identified HIV risk, 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, regular testing for STIs that can facilitate HIV-1 transmission). Inform uninfected individuals about and support their efforts in reducing sexual risk behavior.

Use DESCOVY to reduce the risk of acquiring HIV-1 only in individuals confirmed to be HIV-1 negative. HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking only DESCOVY, because DESCOVY alone does not constitute a complete regimen for HIV-1 treatment [see Microbiology (12.4)]; therefore, care should be taken to minimize the risk of initiating or continuing DESCOVY before confirming the individual is HIV-1 negative.

• Some HIV-1 tests only detect anti-HIV antibodies and may not identify HIV-1 during the acute stage of infection. Prior to initiating DESCOVY for HIV-1 PrEP, ask seronegative individuals about recent (in past month) potential exposure events (e.g., condomless sex or condom breaking during sex with a partner of unknown HIV-1 status or unknown viremic status, or a recent STI), and evaluate for current or recent signs or symptoms consistent with acute HIV-1 infection (e.g., fever, fatigue, myalgia, skin rash).
• If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, use a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection.

While using DESCOVY for HIV-1 PrEP, HIV-1 testing should be repeated at least every 3 months, and upon diagnosis of any other STIs.

• If an HIV-1 test indicates possible HIV-1 infection, or if symptoms consistent with acute HIV-1 infection develop following a potential exposure event, convert the HIV-1 PrEP regimen to an HIV treatment regimen until negative infection status is confirmed using a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection.

Counsel HIV-1 uninfected individuals to strictly adhere to the once daily DESCOVY dosing schedule. The effectiveness of DESCOVY in reducing the risk of acquiring HIV-1 is strongly correlated with adherence, as demonstrated by measurable drug levels in a clinical trial of DESCOVY for HIV-1 PrEP. Some individuals, such as adolescents, may benefit from more frequent visits and counseling to support adherence [see Use in Specific Populations (8.4), Microbiology (12.4), and Clinical Studies (14.3)].

5.3 Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in HIV-1 infected patients treated with combination antiretroviral therapy, including FTC, a component of DESCOVY. During the initial phase of combination antiretroviral treatment, HIV-1 infected patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves' disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

5.4 New Onset or Worsening Renal Impairment

Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with TAF-containing products; while most of these cases were characterized by potential confounders that may have contributed to the reported renal events, it is also possible these factors may have predisposed patients to tenofovir-related adverse events [see Adverse Reactions (6.1, 6.2)]. DESCOVY is not recommended in individuals with estimated creatinine clearance of 15 to below 30 mL per minute, or in individuals with estimated creatinine clearance below 15 mL per minute who are not receiving chronic hemodialysis.

Individuals taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents including non-steroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions.

Prior to or when initiating DESCOVY, and during treatment with DESCOVY on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all individuals. In individuals with chronic kidney disease, also assess serum phosphorus. Discontinue DESCOVY in individuals who develop clinically significant decreases in renal function or evidence of Fanconi syndrome.

5.5 Lactic Acidosis/Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including emtricitabine, a component of DESCOVY, and tenofovir DF, another prodrug of tenofovir, alone or in combination with other antiretrovirals. Treatment with DESCOVY should be suspended in any individual who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug (or a drug given in various combinations with other concomitant therapy) cannot be directly compared to rates in the clinical trials of another drug (or drug given in the same or different combination therapy) and may not reflect the rates observed in practice.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of products containing TAF. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and Subcutaneous Tissue Disorders

Angioedema, urticaria, and rash

Renal and Urinary Disorders

Acute renal failure, acute tubular necrosis, proximal renal tubulopathy, and Fanconi syndrome

7.1 Potential for Other Drugs to Affect One or More Components of DESCOVY

TAF, a component of DESCOVY, is a substrate of P-gp, BCRP, OATP1B1, and OATP1B3. Drugs that strongly affect P-gp and BCRP activity may lead to changes in TAF absorption (see Table 5). Drugs that induce P-gp activity are expected to decrease the absorption of TAF, resulting in decreased plasma concentration of TAF, which may lead to loss of therapeutic effect of DESCOVY and development of resistance. Coadministration of DESCOVY with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of TAF. TAF is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or UGT1A1. TAF is a weak inhibitor of CYP3A in vitro. TAF is not an inhibitor or inducer of CYP3A in vivo.

7.2 Drugs Affecting Renal Function

Because FTC and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of DESCOVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions. Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4)].

7.3 Established and Other Potentially Significant Interactions

Table 6 provides a listing of established or potentially clinically significant drug interactions with recommended steps to prevent or manage the drug interaction (the table is not all inclusive). The drug interactions described are based on studies conducted with either DESCOVY, the components of DESCOVY (emtricitabine and tenofovir alafenamide) as individual agents, or are predicted drug interactions that may occur with DESCOVY. For magnitude of interaction, see Clinical Pharmacology (12.3).

7.4 Drugs without Clinically Significant Interactions with DESCOVY

Based on drug interaction studies conducted with the components of DESCOVY, no clinically significant drug interactions have been either observed or are expected when DESCOVY is combined with the following antiretroviral agents: atazanavir with ritonavir or cobicistat, darunavir with ritonavir or cobicistat, dolutegravir, efavirenz, ledipasvir, lopinavir/ritonavir, maraviroc, nevirapine, raltegravir, rilpivirine, and sofosbuvir. No clinically significant drug interactions have been either observed or are expected when DESCOVY is combined with the following drugs: buprenorphine, itraconazole, ketoconazole, lorazepam, methadone, midazolam, naloxone, norbuprenorphine, norgestimate/ethinyl estradiol, and sertraline.

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

In clinical trials of an FTC+TAF-containing regimen for treatment of HIV-1, 80 of the 97 subjects enrolled aged 65 years and over received FTC+TAF and EVG+COBI. No differences in safety or efficacy have been observed between elderly subjects and adults between 18 and less than 65 years of age.

8.6 Renal Impairment

No dosage adjustment of DESCOVY is recommended in individuals with estimated creatinine clearance greater than or equal to 30 mL per minute, or in adults with ESRD (estimated creatinine clearance below 15 mL per minute) who are receiving chronic hemodialysis. On days of hemodialysis, administer the daily dose of DESCOVY after completion of hemodialysis treatment.

Safety and effectiveness of DESCOVY coadministered with an HIV-1 protease inhibitor that is administered with either ritonavir or cobicistat have not been established in patients with ESRD [see Dosage and Administration (2.3)].

DESCOVY is not recommended in individuals with severe renal impairment (estimated creatinine clearance of 15 to below 30 mL per minute), or in individuals with ESRD who are not receiving chronic hemodialysis, as the safety of DESCOVY has not been established in these populations [see Dosage and Administration (2.6) and Clinical Studies (14.2)].

8.7 Hepatic Impairment

No dosage adjustment of DESCOVY is recommended in individuals with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. DESCOVY has not been studied in individuals with severe hepatic impairment (Child-Pugh Class C) [see Clinical Pharmacology (12.3)].

Emtricitabine (FTC): Limited clinical experience is available at doses higher than the recommended dose of FTC in DESCOVY. In one clinical pharmacology study, single doses of FTC 1200 mg (6 times the FTC dose in DESCOVY) were administered to 11 subjects. No severe adverse reactions were reported. The effects of higher doses are not known.

Hemodialysis treatment removes approximately 30% of the FTC dose over a 3-hour dialysis period starting within 1.5 hours of FTC dosing (blood flow rate of 400 mL per minute and a dialysate flow rate of 600 mL per minute). It is not known whether FTC can be removed by peritoneal dialysis.

Tenofovir Alafenamide (TAF): Limited clinical experience is available at doses higher than the recommended dose of TAF. A single dose of 125 mg TAF (5 times the TAF dose in 200/25 mg DESCOVY) was administered to 48 healthy subjects; no serious adverse reactions were reported. The effects of higher doses are unknown. Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%.

Emtricitabine: The chemical name of FTC is 4-amino-5-fluoro-1-(2R-hydroxymethyl-1,3-oxathiolan-5S-yl)-(1H)-pyrimidin-2-one. FTC is the (-)enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5 position.

FTC has a molecular formula of C8H10FN3O3S and a molecular weight of 247.24 and has the following structural formula:

FTC is a white to off-white powder with a solubility of approximately 112 mg per mL in water at 25 °C.

Tenofovir Alafenamide: The chemical name of tenofovir alafenamide fumarate drug substance is L-alanine, N-[(S)-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphinyl]-, 1-methylethyl ester, (2E)-2-butenedioate (2:1).

Tenofovir alafenamide fumarate has an empirical formula of C21H29O5N6P∙½(C4H4O4) and a formula weight of 534.50 and has the following structural formula:

Tenofovir alafenamide fumarate is a white to off-white or tan powder with a solubility of 4.7 mg per mL in water at 20 °C.

12.1 Mechanism of Action

DESCOVY is a fixed dose combination of antiretroviral drugs emtricitabine (FTC) and tenofovir alafenamide (TAF) [see Microbiology (12.4)].

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.4 Microbiology

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

Minimal to slight infiltration of mononuclear cells in the posterior uvea was observed in dogs with similar severity after three- and nine-month administration of TAF; reversibility was seen after a three-month recovery period. No eye toxicity was observed in the dog at systemic exposures of 5 (TAF) and 15 (tenofovir) times the exposure seen in humans with the recommended daily TAF dose in DESCOVY.

14.1 Overview of Clinical Trials

The efficacy and safety of DESCOVY have been evaluated in the trials summarized in Table 15.

14.2 Clinical Trial Results for Treatment of HIV-1

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.

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.

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.

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)].