Tenofovir Alafenamide

INDICATIONS AND USAGE HIV-1 Treatment ( 1.1 ): DESCOVY is a two-drug combination of emtricitabine (FTC) and tenofovir alafenamide (TAF), both HIV nucleoside analog reverse transcriptase inhibitors (NRTIs), and is indicated: in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and adolescent patients weighing at least 35 kg. for the treatment of HIV-1 infection in pediatric patients weighing at least 14 kg to less than 35 kg in combination with other antiretroviral agents, including darunavir and cobicistat but not other protease inhibitors that require a CYP3A inhibitor. HIV-1 PrEP ( 1.2 ): 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. Limitations of Use ( 1.2 ): The indication does not include use of DESCOVY in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated. 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 adolescent patients weighing at least 35 kg. DESCOVY is indicated for the treatment of HIV-1 infection in pediatric patients weighing at least 14 kg to less than 35 kg in combination with other antiretroviral agents, including darunavir and cobicistat but not other protease inhibitors that require a CYP3A inhibitor. 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) ]. Limitations of Use: The indication does not include use of DESCOVY in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated [see Clinical Studies (14.3) ].

DOSAGE AND ADMINISTRATION Testing: Prior to or when initiating DESCOVY, test for hepatitis B virus infection. Prior to or when initiating DESCOVY, and during use 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. ( 2.1 ) HIV-1 Screening: 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). ( 2.2 ) Recommended dosage: Treatment of HIV-1 Infection: Adult and pediatric patients weighing at least 35 kg: One 200 mg/25 mg tablet once daily with or without food. ( 2.3 ) Pediatric patients receiving DESCOVY with other antiretroviral agents, including darunavir and cobicistat but not other protease inhibitors administered with either ritonavir or cobicistat, and weighing: at least 25 to less than 35 kg: One 200 mg/25 mg tablet once daily with or without food. ( 2.4 ) at least 14 to less than 25 kg: One 120 mg/15 mg tablet once daily with or without food. ( 2.4 ) HIV-1 PrEP: One 200 mg/25 mg tablet once daily with or without food in individuals with body weight at least 35 kg. ( 2.5 ) Renal impairment: DESCOVY is not recommended in individuals with estimated creatinine clearance of 15 to below 30 mL per minute, or below 15 mL per minute who are not receiving chronic hemodialysis. ( 2.6 ) 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 for treatment of HIV-1 in pediatric patients is based on body weight and is 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 receiving DESCOVY with other antiretroviral agents, including darunavir (DRV) and cobicistat (COBI) but not including other HIV-1 protease inhibitors that are administered with either ritonavir or cobicistat. Table 1 Dosing for Treatment of HIV-1 Infection in Pediatric Patients Weighing 14 to Less than 35 kg Body Weight (kg) DESCOVY Dosage 25 kg to less than 35 kg One tablet containing 200 mg of FTC and 25 mg of TAF taken orally once daily 14 kg to less than 25 kg One tablet containing 120 mg of FTC and 15 mg of TAF taken orally once daily 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: adults and adolescents without HIV-1 weighing at least 35 kg and with a creatinine clearance greater than or equal to 30 mL per minute; or adults without HIV-1 and 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) ] .

WARNINGS AND PRECAUTIONS Comprehensive management to reduce the risk of sexually transmitted infections (STIs), including HIV-1, when DESCOVY is used for HIV-1 PrEP: Counsel on adherence to daily dosing and safer sex practices, including condoms, to reduce the risk of STIs. ( 5.2 ) Management to reduce the risk of acquiring HIV-1 drug resistance when DESCOVY is used for HIV-1 PrEP: refer to full prescribing information for additional detail. ( 5.2 ) Immune reconstitution syndrome during treatment of HIV-1 infection: May necessitate further evaluation and treatment. ( 5.3 ) New onset or worsening renal impairment: Assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein when initiating DESCOVY and during use on a clinically appropriate schedule in all individuals. Also assess serum phosphorus in individuals with chronic kidney disease. ( 5.4 ) Lactic acidosis/severe hepatomegaly with steatosis: Discontinue DESCOVY in individuals who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity. ( 5.5 ) 5.1 Severe Acute Exacerbation of Hepatitis B in Individuals with HBV 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 individuals with HBV who have discontinued products containing FTC and/or tenofovir disoproxil fumarate (TDF) and may occur with discontinuation of DESCOVY. Individuals 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. Individuals without HBV 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 individuals without HIV-1 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 individuals without HIV-1 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 patients with HIV-1 treated with combination antiretroviral therapy, including FTC, a component of DESCOVY. During the initial phase of combination antiretroviral treatment, patients with HIV-1 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 DESCO

CONTRAINDICATIONS DESCOVY for HIV-1 PrEP is contraindicated in individuals with unknown or positive HIV-1 status [see Warnings and Precautions (5.2) ]. DESCOVY for HIV-1 PrEP is contraindicated in individuals with unknown or positive HIV-1 status. ( 4 )

DRUG INTERACTIONS Consult the Full Prescribing Information prior to and during use for potential drug interactions. ( 7 , 12.3 ) 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 6 ). 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) . Table 6 Established and Other Potentially Significant This table is not all inclusive. Drug Interactions Concomitant Drug Class: Drug Name Effect on Concentration ↓=Decrease Clinical Comment ↑= Increase Antiretroviral Agents: Protease Inhibitors (PI) tipranavir/ritonavir ↓ TAF Coadministration with DESCOVY is not recommended. atazanavir/cobicistat ↑ TAF Coadministration with DESCOVY in pediatric patients weighing 14 to < 35 kg is not recommended [see Use in Specific Populations (8.4) ] . Other Agents Anticonvulsants: carbamazepine oxcarbazepine phenobarbital phenytoin ↓ TAF Consider alternative anticonvulsant. Antimycobacterials: rifabutin rifampin rifapentine ↓ TAF Coadministration of DESCOVY with rifabutin, rifampin, or rifapentine is not recommended. Herbal Products: St. John’s wort (Hypericum perforatum) ↓ TAF Coadministration of DESCOVY with St. John’s wort is not recommended. 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, atazanavir with cobicistat (in those weighing ≥35 kg), 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.

ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Severe Acute Exacerbations of Hepatitis B [see Warnings and Precautions (5.1) ] . Immune Reconstitution Syndrome [see Warnings and Precautions (5.3) ] . New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.4) ] . Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.5) ]. In participants with HIV-1, the most common adverse reaction (incidence greater than or equal to 10%, all grades) was nausea. ( 6.1 ) In adults without HIV-1 in a PrEP trial, the most common adverse reaction (incidence greater than or equal to 5%, all grades) was diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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. Adverse Reactions in Clinical Trials of FTC+TAF with Elvitegravir (EVG) plus Cobicistat (COBI) in Treatment-Naïve Adults with HIV-1 In pooled 48-week trials of antiretroviral treatment-naïve adult participants with HIV-1, the most common adverse reaction in participants treated with FTC+TAF with EVG+COBI (N=866) (incidence greater than or equal to 10%, all grades) was nausea (10%). In this treatment group, 0.9% of participants discontinued FTC+TAF with EVG+COBI due to adverse events during the 48-week treatment period [see Clinical Studies (14.2) ] . The safety profile was similar in virologically-suppressed adults with HIV-1 who were switched to FTC+TAF with EVG+COBI (N=799). Antiretroviral treatment-naïve adult participants with HIV-1 treated with FTC+TAF with EVG+COBI experienced mean increases of 30 mg/dL of total cholesterol, 15 mg/dL of LDL cholesterol, 7 mg/dL of HDL cholesterol, and 29 mg/dL of triglycerides after 48 weeks of use. Renal Laboratory Tests In two 48-week trials in antiretroviral treatment-naïve adults with HIV-1 treated with FTC+TAF with EVG+COBI (N=866) with a median baseline eGFR of 115 mL per minute, mean serum creatinine increased by 0.1 mg per dL from baseline to Week 48. Median urine protein-to-creatinine ratio (UPCR) was 44 mg per gram at baseline and at Week 48. In a 48-week trial in virologically-suppressed TDF-treated adults with HIV-1 who switched to FTC+TAF with EVG+COBI (N=959) with a mean baseline eGFR of 112 mL per minute, mean serum creatinine was similar to baseline at Week 48; median UPCR was 61 mg per gram at baseline and 46 mg per gram at Week 48. Across these trials, renal serious adverse events or discontinuations due to renal adverse reactions were encountered in less than 1% of participants treated with FTC+TAF with EVG+COBI. In a 24-week trial in adults with HIV-1 and renal impairment (baseline eGFR 30 to 69 mL per minute) who received FTC+TAF with EVG+COBI (N=248), mean serum creatinine was 1.5 mg per dL at both baseline and Week 24. Median UPCR was 161 mg per gram at baseline and 93 mg per gram at Week 24. FTC+TAF with EVG+COBI was permanently discontinued due to worsening renal function in two of 80 (3%) participants. Bone Mineral Density Effects In the pooled analysis of two 48-week trials of antiretroviral treatment-naïve adult participants with HIV-1, bone mineral density (BMD) from baseline to Week 48 was assessed by dual-energy X-ray absorptiometry (DXA). Mean BMD decreased from baseline to Week 48 −1.30% with FTC+TAF with EVG+COBI at the lumbar spine and −0.66% at the total hip. BMD declines of 5% or greater at the lumbar spine were experienced by 10% of FTC+TAF with EVG+COBI participants. BMD declines of 7% or greater at the femoral neck were experienced by 7% of FTC+TAF with EVG+COBI participants. The long-term clinical significance of these BMD changes is not known. In 799 virologically-suppressed TDF-treated adult participants with HIV-1 that switched to FTC+TAF with EVG+COBI, at Week 48 mean BMD increased (1.86% lumbar spine, 1.95% total hip). BMD declines of 5% or greater at the lumbar spine were experienced by 1% of FTC+TAF with EVG+COBI participants. BMD declines of 7% or greater at the femoral neck were experienced by 1% of FTC+TAF with EVG+COBI participants. Adverse Reactions in a Clinical Trial of FTC+TAF with EVG+COBI in Virologically-Suppressed Adults with HIV-1 and End Stage Renal Disease (ESRD) Receiving Chronic Hemodialysis In a 48-week trial of virologically-suppressed adult participants with HIV-1 and end stage renal disease (ESRD) (estimated creatinine clearance of less than 15 mL/min) on chronic hemodialysis treated with FTC+TAF with EVG+COBI (N=55), the most commonly reported adverse reaction (adverse event assessed as causally related by investigator and all grades) was nausea (7%). Serious adverse events were reported in 53% of participants and the most common serious adverse events were pneumonia (13%), fluid overload (7%), hyperkalemia (7%) and osteomyelitis (7%). Overall 5% of participants permanently discontinued treatment due to an adverse event. Adverse Reactions in Clinical Trials in Pediatric Participants with HIV-1 Study 106: Adverse Reactions in a Clinical Trial of FTC+TAF with EVG+COBI in Pediatric Participants Weighing at Least 25 kg The safety profile of FTC+TAF in pediatric participants weighing at least 25 kg is informed by an open-label trial of antiretroviral treatment-naïve pediatric participants with HIV-1 between the ages of 12 to less than 18 years weighing at least 35 kg through 48 weeks (N=50; cohort 1) and virologically-suppressed participants with HIV-1 between the ages of 6 to less than 12 years weighing at least 25 kg (N=52; cohort 2). Participants received FTC+TAF with EVG+COBI through 48 weeks. With the exception of a decrease in the mean CD4+ cell count observed in cohort 2, the safety of this combination was similar to that in adults. Bone Mineral Density Effects Cohort 1: Treatment-naïve adolescents (12 to less than 18 years; at least 35 kg) Among the participants in cohort 1 receiving FTC+TAF with EVG+COBI, mean BMD increased from baseline to Week 48, +4.2% at the lumbar spine and +1.3% for the total body less head (TBLH). Mean changes from baseline BMD Z-scores were −0.07 for lumbar spine and −0.20 for TBLH at Week 48. One participant had significant (at least 4%) lumbar spine BMD loss at Week 48. Cohort 2: Virologically-suppressed children (6 to less than 12 years; at least 25 kg) Among the participants in cohort 2 receiving FTC+TAF with EVG+COBI, mean BMD increased from baseline to Week 48, +3.9% at the lumbar spine and +4.2% for TBLH. Mean changes from baseline BMD Z-scores were -0.24 for lumbar spine and -0.19 for TBLH at Week 48. Six participants had significant (at least 4%) lumbar spine BMD loss at Week 48 and 2 participants also had at least 4% TBLH BMD loss at Week 48. Change from Baseline in CD4+ cell counts Cohort 2: Virologically-suppressed children (6 to less than 12 years; at least 25 kg) Cohort 2 evaluated pediatric participants (N=52) who were virologically-suppressed and who switched from their antiretroviral regimen to FTC+TAF with EVG+COBI. Although all participants had HIV-1 RNA < 50 copies/mL, there was a decrease from baseline in CD4+ cell count at Weeks 24 and 48. The mean baseline and mean change from baseline in CD4+ cell count and in CD4% from Week 2 to Week 48 are presented in Table 2 . All participants maintained their CD4+ cell counts above 400 cells/mm 3 [see Use in Specific Populations (8.4) ]. Table 2 Mean Change in CD4+ Count and CD4 Percentage from Baseline to Week 48 in Virologically-Suppressed Pediatric Participants from 6 to <12 Years Who Switched to FTC+

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