FDA label 4e3fe418-d185-3024-e054-00144ff88e88

WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS B Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals [See Warnings and Precautions (5.1) ]. EMTRIVA is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of EMTRIVA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued EMTRIVA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue EMTRIVA. If appropriate, initiation of anti-hepatitis B therapy may be warranted [See Warnings and Precautions (5.2) ]. WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS B See full prescribing information for complete boxed warning . Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs. ( 5.1 ) Emtriva is not approved for the treatment of chronic Hepatitis B virus (HBV) infection. Severe acute exacerbations of Hepatitis B have been reported in patients who have discontinued EMTRIVA. Hepatic function should be monitored closely in patients coinfected with HIV-1 and HBV. If appropriate, initiation of anti-Hepatitis B therapy may be warranted. ( 5.2 )

5 WARNINGS AND PRECAUTIONS Products with same active ingredient: Do not use with other emtricitabine-containing products (e.g., ATRIPLA, COMPLERA, STRIBILD, and TRUVADA). ( 5.3 ) Redistribution/accumulation of body fat: Observed in patients receiving antiretroviral therapy. ( 5.5 ) Immune reconstitution syndrome: May necessitate further evaluation and treatment. ( 5.6 ) 5.1 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 alone or in combination, including emtricitabine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for liver diseases; however, cases have also been reported in patients with no known risk factors. Treatment with EMTRIVA should be suspended in any patient 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). 5.2 Patients Coinfected with HIV-1 and HBV It is recommended that all patients with HIV-1 be tested for the presence of chronic Hepatitis B virus (HBV) before initiating antiretroviral therapy. EMTRIVA is not approved for the treatment of chronic HBV infection and the safety and efficacy of EMTRIVA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of Hepatitis B have been reported in patients after the discontinuation of EMTRIVA. In some patients infected with HBV and treated with EMTRIVA, the exacerbations of hepatitis B were associated with liver decompensation and liver failure. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue EMTRIVA. If appropriate, initiation of anti-Hepatitis B therapy may be warranted. 5.3 Coadministration with Related Products EMTRIVA is a component of ATRIPLA (a fixed-dose combination of efavirenz, emtricitabine, and tenofovir disoproxil fumarate), COMPLERA (a fixed-dose combination of emtricitabine, rilpivirine, and tenofovir disoproxil fumarate), STRIBILD (a fixed-dose combination of elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate), and TRUVADA (a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate). EMTRIVA should not be coadministered with ATRIPLA, COMPLERA, STRIBILD, or TRUVADA. Due to similarities between emtricitabine and lamivudine, EMTRIVA should not be coadministered with other drugs containing lamivudine, including Combivir (lamivudine/zidovudine), Epivir or Epivir-HBV (lamivudine), Epzicom (abacavir sulfate/lamivudine), or Trizivir (abacavir sulfate/lamivudine/zidovudine). 5.4 New Onset or Worsening Renal Impairment Emtricitabine is principally eliminated by the kidney. Reduction of the dosage of EMTRIVA is recommended for patients with impaired renal function [See Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ]. 5.5 Fat Redistribution Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established. 5.6 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including EMTRIVA. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as infection, cytomegalovirus, pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment. Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including EMTRIVA. During the initial phase of combination antiretroviral treatment, 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, and Guillain-Barré syndrome) 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.

6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Lactic acidosis/severe hepatomegaly with steatosis [See Boxed Warning , Warnings and Precautions (5.1) ]. Severe acute exacerbations of Hepatitis B [See Boxed Warning , Warnings and Precautions (5.2) ]. Immune reconstitution syndrome [See Warnings and Precautions (5.6) ]. Most common adverse reactions (incidence ≥10%) are headache, diarrhea, nausea, fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis. Skin hyperpigmentation was very common (≥10%) in pediatric patients. ( 6 ) 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 Adverse Reactions from Clinical Trials Experience Clinical Trials in Adult Subjects More than 2,000 adult subjects with HIV-1 infection have been treated with EMTRIVA alone or in combination with other antiretroviral agents for periods of 10 days to 200 weeks in clinical trials. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions (incidence greater than or equal to 10%, any severity) identified from any of the 3 large controlled clinical trials include headache, diarrhea nausea, fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis. Studies 301A and 303 - Treatment Emergent Adverse Reactions: The most common adverse reactions that occurred in subjects receiving EMTRIVA with other antiretroviral agents in clinical trials 301A and 303 were headache, diarrhea, nausea, and rash, which were generally of mild to moderate severity. Approximately 1% of subjects discontinued participation in the clinical trials due to these events. All adverse reactions were reported with similar frequency in EMTRIVA and control treatment groups with the exception of skin discoloration which was reported with higher frequency in the EMTRIVA treated group. Skin discoloration, manifested by hyperpigmentation on the palms and/or soles was generally mild and asymptomatic. The mechanism and clinical significance are unknown. A summary of EMTRIVA treatment-emergent clinical adverse reactions in Studies 301A and 303 is provided in Table 2. Table 2 Selected Treatment-Emergent Adverse Reactions (All Grades, Regardless of Causality) Reported in ≥3% of EMTRIVA-Treated Subjects in Either Study 301A or 303 (0–48 Weeks) 303 301A EMTRIVA + ZDV/d4T + NNRTI/PI (N=294) Lamivudine + ZDV/d4T + NNRTI/PI (N=146) EMTRIVA + didanosine + efavirenz (N=286) Stavudine + didanosine + efavirenz (N=285) Body as a Whole Abdominal pain 8% 11% 14% 17% Asthenia 16% 10% 12% 17% Headache 13% 6% 22% 25% Digestive System Diarrhea 23% 18% 23% 32% Dyspepsia 4% 5% 8% 12% Nausea 18% 12% 13% 23% Vomiting 9% 7% 9% 12% Musculoskeletal Arthralgia 3% 4% 5% 6% Myalgia 4% 4% 6% 3% Nervous System Abnormal dreams 2% <1% 11% 19% Depressive disorders 6% 10% 9% 13% Dizziness 4% 5% 25% 26% Insomnia 7% 3% 16% 21% Neuropathy/peripheral neuritis 4% 3% 4% 13% Paresthesia 5% 7% 6% 12% Respiratory Increased cough 14% 11% 14% 8% Rhinitis 18% 12% 12% 10% Skin Rash event Rash event includes rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, and allergic reaction. 17% 14% 30% 33% Studies 301A and 303 - Laboratory Abnormalities : Laboratory abnormalities in these trials occurred with similar frequency in the EMTRIVA and comparator groups. A summary of Grades 3–4 laboratory abnormalities is provided in Table 3 below. Table 3 Treatment-Emergent Grades 3–4 Laboratory Abnormalities Reported in ≥1% of EMTRIVA-Treated Subjects in Either Study 301A or 303 303 301A EMTRIVA + ZDV/d4T + NNRTI/PI (N=294) Lamivudine + ZDV/d4T + NNRTI/PI (N=146) EMTRIVA + Didanosine + Efavirenz (N=286) Stavudine + Didanosine + Efavirenz (N=285) Percentage with grade 3 or grade 4 laboratory abnormality 31% 28% 34% 38% ALT (>5.0 × ULN ULN = Upper limit of normal ) 2% 1% 5% 6% AST (>5.0 × ULN) 3% <1% 6% 9% Bilirubin (>2.5 × ULN) 1% 2% <1% <1% Creatine kinase (>4.0 × ULN) 11% 14% 12% 11% Neutrophils (<750 mm 3 ) 5% 3% 5% 7% Pancreatic amylase (>2.0 × ULN) 2% 2% <1% 1% Serum amylase (>2.0 × ULN) 2% 2% 5% 10% Serum glucose <40 or >250 mg/dL) 3% 3% 2% 3% Serum lipase (>2.0 × ULN) <1% <1% 1% 2% Triglycerides (>750 mg/dL) 10% 8% 9% 6% Study 934 - Treatment Emergent Adverse Reactions: In Study 934, 511 antiretroviral-naïve subjects received either VIREAD ® + EMTRIVA administered in combination with efavirenz (N=257) or zidovudine/lamivudine administered in combination with efavirenz (N=254). Adverse reactions observed in this trial were generally consistent with those seen in previous trials in treatment-experienced or treatment-naïve subjects (Table 4). Table 4 Selected Treatment-Emergent Adverse Reactions Frequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug. (Grades 2–4) Reported in ≥5% in Any Treatment Group in Study 934 (0–144 Weeks) TDF From Weeks 96 to 144 of the trial, subjects received TRUVADA with efavirenz in place of VIREAD + EMTRIVA with efavirenz. + EMTRIVA + EFV AZT/3TC + EFV N=257 N=254 Gastrointestinal Disorder Diarrhea 9% 5% Nausea 9% 7% Vomiting 2% 5% General Disorders and Administration Site Condition Fatigue 9% 8% Infections and Infestations Sinusitis 8% 4% Upper respiratory tract infections 8% 5% Nasopharyngitis 5% 3% Nervous System Disorders Headache 6% 5% Dizziness 8% 7% Psychiatric Disorders Depression 9% 7% Insomnia 5% 7% Skin and Subcutaneous Tissue Disorders Rash event Rash event includes rash, exfoliative rash, rash generalized, rash macular, rash maculo-papular, rash pruritic, and rash vesicular. 7% 9% Study 934 – Laboratory Abnormalities: Significant laboratory abnormalities observed in this trial are shown in Table 5. Table 5 Significant Laboratory Abnormalities Reported in ≥1% of Subjects in Any Treatment Group in Study 934 (0–144 Weeks) TDF From Weeks 96 to 144 of the trial, subjects received TRUVADA with efavirenz in place of VIREAD + EMTRIVA with efavirenz. + EMTRIVA + EFV AZT/3TC + EFV N=257 N=254 Any ≥ Grade 3 Laboratory Abnormality 30% 26% Fasting Cholesterol (>240 mg/dL) 22% 24% Creatine Kinase (M: >990 U/L) (F: >845 U/L) 9% 7% Serum Amylase (>175 U/L) 8% 4% Alkaline Phosphatase (>550 U/L) 1% 0% AST (M: >180 U/L) (F: >170 U/L) 3% 3% ALT (M: >215 U/L) (F: >170 U/L) 2% 3% Hemoglobin (<8.0 mg/dL) 0% 4% Hyperglycemia (>250 mg/dL) 2% 1% Hematuria (>75 RBC/HPF) 3% 2% Glycosuria (3+) <1% 1% Neutrophils (<750/mm 3 ) 3% 5% Fasting Triglycerides (>750 mg/dL) 4% 2% Clinical Trials in Pediatric Subjects Assessment of adverse reactions is based on data from Study 203, an open label, uncontrolled trial of 116 HIV-1-infected pediatric subjects who received emtricitabine through 48 weeks. The adverse reaction profile in pediatric subjects was generally comparable to that observed in clinical trials of EMTRIVA in adult subjects [See Adverse Reactions (6.1) ] . Hyperpigmentation was more frequent in children. Additional adverse reactions identified from this trial include anemia. Selected treatment-emergent adverse events, regardless of causality, reported in subjects during 48 weeks of treatment were the following: infection (44%), hyperpigmentation (32%), increased cough (28%), vomiting (23%), otitis media (23%), rash (21%), rhinitis (20%), diarrhea (20%), fever (18%), pneumonia (15%), gastroenteritis (11%), abdominal pain (10%), and anemia (7%). Treatment-emergent grades 3–4 laboratory abnormalities were experienced by 9% of pediatric subjects, including elevated amylase (>2.0 × ULN) (n=4), decreased neutrophils (<750/mm 3 ) (n=3), elevated ALT (>5 × ULN) (n=2), elevated CPK (>4 × ULN) (n=2) and one subject each with elevated bilirubin (>3.0 × ULN), elevated GGT (>10 × ULN), elevated lipase (>2.5 × ULN), decreased hemoglobin (<7 g/dL), and decreased glucose (<40 mg/dL).

<table ID="table2" width="80%"> <caption>Table 2 Selected Treatment-Emergent Adverse Reactions (All Grades, Regardless of Causality) Reported in &#x2265;3% of EMTRIVA-Treated Subjects in Either Study 301A or 303 (0&#x2013;48 Weeks)</caption> <col align="left" valign="middle" width="40%"/> <col align="center" valign="middle" width="15%"/> <col align="center" valign="middle" width="15%"/> <col align="center" valign="middle" width="15%"/> <col align="center" valign="middle" width="15%"/> <thead> <tr> <th rowspan="2" styleCode="Lrule Rrule"/> <th colspan="2" styleCode="Rrule Botrule">303</th> <th colspan="2" styleCode="Rrule Botrule">301A</th> </tr> <tr> <th align="center" styleCode="Rrule">EMTRIVA + ZDV/d4T + NNRTI/PI (N=294) </th> <th styleCode="Rrule">Lamivudine + ZDV/d4T + NNRTI/PI (N=146) </th> <th styleCode="Rrule">EMTRIVA + didanosine + efavirenz (N=286) </th> <th styleCode="Rrule">Stavudine + didanosine + efavirenz (N=285) </th> </tr> </thead> <tbody> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Body as a Whole</td> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Abdominal pain</td> <td styleCode="Rrule">8%</td> <td styleCode="Rrule">11%</td> <td styleCode="Rrule">14%</td> <td styleCode="Rrule">17%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Asthenia</td> <td styleCode="Rrule">16%</td> <td styleCode="Rrule">10%</td> <td styleCode="Rrule">12%</td> <td styleCode="Rrule">17%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Headache</td> <td styleCode="Rrule">13%</td> <td styleCode="Rrule">6%</td> <td styleCode="Rrule">22%</td> <td styleCode="Rrule">25%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Digestive System</td> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Diarrhea</td> <td styleCode="Lrule">23%</td> <td styleCode="Lrule">18%</td> <td styleCode="Lrule">23%</td> <td styleCode="Lrule Rrule">32%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Dyspepsia</td> <td styleCode="Lrule">4%</td> <td styleCode="Lrule">5%</td> <td styleCode="Lrule">8%</td> <td styleCode="Lrule Rrule">12%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Nausea</td> <td styleCode="Lrule">18%</td> <td styleCode="Lrule">12%</td> <td styleCode="Lrule">13%</td> <td styleCode="Lrule Rrule">23%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Vomiting</td> <td styleCode="Lrule">9%</td> <td styleCode="Lrule">7%</td> <td styleCode="Lrule">9%</td> <td styleCode="Lrule Rrule">12%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Musculoskeletal</td> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Arthralgia</td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">4%</td> <td styleCode="Rrule">5%</td> <td styleCode="Rrule">6%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Myalgia</td> <td styleCode="Rrule">4%</td> <td styleCode="Rrule">4%</td> <td styleCode="Rrule">6%</td> <td styleCode="Rrule">3%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Nervous System</td> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Abnormal dreams</td> <td styleCode="Rrule">2%</td> <td styleCode="Rrule">&lt;1%</td> <td styleCode="Rrule">11%</td> <td styleCode="Rrule">19%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Depressive disorders</td> <td styleCode="Rrule">6%</td> <td styleCode="Rrule">10%</td> <td styleCode="Rrule">9%</td> <td styleCode="Rrule">13%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Dizziness</td> <td styleCode="Rrule">4%</td> <td styleCode="Rrule">5%</td> <td styleCode="Rrule">25%</td> <td styleCode="Rrule">26%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Insomnia</td> <td styleCode="Rrule">7%</td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">16%</td> <td styleCode="Rrule">21%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Neuropathy/peripheral neuritis</td> <td styleCode="Rrule">4%</td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">4%</td> <td styleCode="Rrule">13%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Paresthesia</td> <td styleCode="Rrule">5%</td> <td styleCode="Rrule">7%</td> <td styleCode="Rrule">6%</td> <td styleCode="Rrule">12%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Respiratory</td> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Increased cough</td> <td styleCode="Rrule">14%</td> <td styleCode="Rrule">11%</td> <td styleCode="Rrule">14%</td> <td styleCode="Rrule">8%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Rhinitis</td> <td styleCode="Rrule">18%</td> <td styleCode="Rrule">12%</td> <td styleCode="Rrule">12%</td> <td styleCode="Rrule">10%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Skin</td> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule Rrule"> Rash event <footnote ID="K1678">Rash event includes rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, and allergic reaction.</footnote> </td> <td styleCode="Rrule">17%</td> <td styleCode="Rrule">14%</td> <td styleCode="Rrule">30%</td> <td styleCode="Rrule">33%</td> </tr> </tbody> </table>

<table ID="table3" width="80%"> <caption>Table 3 Treatment-Emergent Grades 3&#x2013;4 Laboratory Abnormalities Reported in &#x2265;1% of EMTRIVA-Treated Subjects in Either Study 301A or 303</caption> <col align="left" valign="middle" width="40%"/> <col align="center" valign="middle" width="15%"/> <col align="center" valign="middle" width="15%"/> <col align="center" valign="middle" width="15%"/> <col align="center" valign="middle" width="15%"/> <thead> <tr> <th rowspan="2" styleCode="Lrule Rrule"/> <th colspan="2" styleCode="Rrule Botrule">303</th> <th colspan="2" styleCode="Rrule Botrule">301A</th> </tr> <tr> <th align="center" styleCode="Rrule">EMTRIVA + ZDV/d4T + NNRTI/PI (N=294) </th> <th styleCode="Rrule">Lamivudine + ZDV/d4T + NNRTI/PI (N=146) </th> <th styleCode="Rrule">EMTRIVA + Didanosine + Efavirenz (N=286) </th> <th styleCode="Rrule">Stavudine + Didanosine + Efavirenz (N=285) </th> </tr> </thead> <tbody> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Percentage with grade 3 or grade 4 laboratory abnormality</td> <td styleCode="Rrule">31%</td> <td styleCode="Rrule">28%</td> <td styleCode="Rrule">34%</td> <td styleCode="Rrule">38%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">ALT (&gt;5.0 &#xD7; ULN <footnote ID="K1810">ULN = Upper limit of normal</footnote>) </td> <td styleCode="Rrule">2%</td> <td styleCode="Rrule">1%</td> <td styleCode="Rrule">5%</td> <td styleCode="Rrule">6%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">AST (&gt;5.0 &#xD7; ULN)</td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">&lt;1%</td> <td styleCode="Rrule">6%</td> <td styleCode="Rrule">9%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Bilirubin (&gt;2.5 &#xD7; ULN)</td> <td styleCode="Rrule">1%</td> <td styleCode="Rrule">2%</td> <td styleCode="Rrule">&lt;1%</td> <td styleCode="Rrule">&lt;1%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Creatine kinase (&gt;4.0 &#xD7; ULN) </td> <td styleCode="Rrule">11%</td> <td styleCode="Rrule">14%</td> <td styleCode="Rrule">12%</td> <td styleCode="Rrule">11%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Neutrophils (&lt;750 mm ³) </td> <td styleCode="Rrule">5%</td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">5%</td> <td styleCode="Rrule">7%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Pancreatic amylase (&gt;2.0 &#xD7; ULN) </td> <td styleCode="Rrule">2%</td> <td styleCode="Rrule">2%</td> <td styleCode="Rrule">&lt;1%</td> <td styleCode="Rrule">1%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Serum amylase (&gt;2.0 &#xD7; ULN) </td> <td styleCode="Rrule">2%</td> <td styleCode="Rrule">2%</td> <td styleCode="Rrule">5%</td> <td styleCode="Rrule">10%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Serum glucose &lt;40 or &gt;250 mg/dL) </td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">2%</td> <td styleCode="Rrule">3%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Serum lipase (&gt;2.0 &#xD7; ULN) </td> <td styleCode="Rrule">&lt;1%</td> <td styleCode="Rrule">&lt;1%</td> <td styleCode="Rrule">1%</td> <td styleCode="Rrule">2%</td> </tr> <tr> <td styleCode="Lrule Rrule">Triglycerides (&gt;750 mg/dL) </td> <td styleCode="Rrule">10%</td> <td styleCode="Rrule">8%</td> <td styleCode="Rrule">9%</td> <td styleCode="Rrule">6%</td> </tr> </tbody> </table>

<table ID="table4" width="80%"> <caption>Table 4 Selected Treatment-Emergent Adverse Reactions <footnote ID="K2016">Frequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug.</footnote> (Grades 2&#x2013;4) Reported in &#x2265;5% in Any Treatment Group in Study 934 (0&#x2013;144 Weeks) </caption> <col align="left" valign="middle" width="40%"/> <col align="center" valign="middle" width="30%"/> <col align="center" valign="middle" width="30%"/> <thead> <tr> <th styleCode="Lrule Rrule"/> <th styleCode="Rrule Botrule">TDF <footnote ID="K2038">From Weeks 96 to 144 of the trial, subjects received TRUVADA with efavirenz in place of VIREAD + EMTRIVA with efavirenz.</footnote> + EMTRIVA + EFV </th> <th styleCode="Rrule Botrule">AZT/3TC + EFV</th> </tr> <tr> <th styleCode="Lrule Rrule"/> <th styleCode="Rrule">N=257</th> <th styleCode="Rrule">N=254</th> </tr> </thead> <tbody> <tr> <td styleCode="Lrule">Gastrointestinal Disorder</td> <td styleCode="Lrule Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule"> Diarrhea</td> <td styleCode="Lrule Rrule">9%</td> <td styleCode="Rrule">5%</td> </tr> <tr> <td styleCode="Lrule"> Nausea</td> <td styleCode="Lrule Rrule">9%</td> <td styleCode="Rrule">7%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Vomiting</td> <td styleCode="Lrule Rrule">2%</td> <td styleCode="Rrule">5%</td> </tr> <tr> <td styleCode="Lrule">General Disorders and Administration Site Condition</td> <td styleCode="Lrule Rrule"/> <td styleCode="Rrule"/> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Fatigue</td> <td styleCode="Lrule Rrule">9%</td> <td styleCode="Rrule">8%</td> </tr> <tr> <td styleCode="Lrule">Infections and Infestations</td> <td styleCode="Lrule Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule"> Sinusitis</td> <td styleCode="Lrule Rrule">8%</td> <td styleCode="Rrule">4%</td> </tr> <tr> <td styleCode="Lrule"> Upper respiratory tract infections</td> <td styleCode="Lrule Rrule">8%</td> <td styleCode="Rrule">5%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Nasopharyngitis</td> <td styleCode="Lrule Rrule">5%</td> <td styleCode="Rrule">3%</td> </tr> <tr> <td styleCode="Lrule">Nervous System Disorders</td> <td styleCode="Lrule Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule"> Headache</td> <td styleCode="Lrule Rrule">6%</td> <td styleCode="Rrule">5%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Dizziness</td> <td styleCode="Lrule Rrule">8%</td> <td styleCode="Rrule">7%</td> </tr> <tr> <td styleCode="Lrule">Psychiatric Disorders</td> <td styleCode="Lrule Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule"> Depression</td> <td styleCode="Lrule Rrule">9%</td> <td styleCode="Rrule">7%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Insomnia</td> <td styleCode="Lrule Rrule">5%</td> <td styleCode="Rrule">7%</td> </tr> <tr> <td styleCode="Lrule">Skin and Subcutaneous Tissue Disorders</td> <td styleCode="Lrule Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule"> Rash event <footnote ID="K2221">Rash event includes rash, exfoliative rash, rash generalized, rash macular, rash maculo-papular, rash pruritic, and rash vesicular.</footnote> </td> <td styleCode="Lrule Rrule">7%</td> <td styleCode="Rrule">9%</td> </tr> </tbody> </table>