FDA label bea0f43d-4f45-40d2-b4a4-3ac996bb1626

WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including VIREAD, in combination with other antiretrovirals [See Warnings and Precautions (5.1) ] . Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including VIREAD. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VIREAD. If appropriate, resumption of anti-hepatitis B therapy may be warranted [See Warnings and Precautions (5.2) ] . WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS 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, including VIREAD. ( 5.1 ) Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including VIREAD. Hepatic function should be monitored closely in these patients. If appropriate, resumption of anti-hepatitis B therapy may be warranted. ( 5.2 )

5 WARNINGS AND PRECAUTIONS New onset or worsening renal impairment: Can include acute renal failure and Fanconi syndrome. Assess creatinine clearance (CrCl) before initiating treatment with VIREAD. Monitor CrCl and serum phosphorus in patients at risk. Avoid administering VIREAD with concurrent or recent use of nephrotoxic drugs, including HEPSERA. ( 5.3 ) Products with same active ingredient: Do not use with other tenofovir-containing products (e.g., ATRIPLA and TRUVADA). ( 5.4 ) HIV testing: HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with VIREAD. VIREAD should only be used as part of an appropriate antiretroviral combination regimen in HIV-infected patients with or without HBV coinfection. ( 5.5 ) Decreases in bone mineral density (BMD): Observed in HIV-infected patients. Consider monitoring BMD in patients with a history of pathologic fracture or who are at risk for osteopenia. ( 5.6 ) Redistribution/accumulation of body fat: Observed in HIV-infected patients receiving antiretroviral combination therapy. ( 5.7 ) Immune reconstitution syndrome: Observed in HIV-infected patients. May necessitate further evaluation and treatment. ( 5.8 ) Triple nucleoside-only regimens: Early virologic failure has been reported in HIV-infected patients. Monitor carefully and consider treatment modification. ( 5.9 ) 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, including VIREAD, in combination with 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 disease; however, cases have also been reported in patients with no known risk factors. Treatment with VIREAD 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 Exacerbation of Hepatitis after Discontinuation of Treatment Discontinuation of anti-HBV therapy, including VIREAD, may be associated with severe acute exacerbations of hepatitis. Patients infected with HBV who discontinue VIREAD should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, resumption of anti-hepatitis B therapy may be warranted. 5.3 New Onset or Worsening Renal Impairment Tenofovir is principally eliminated by the kidney. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of VIREAD [See Adverse Reactions (6.2) ] . It is recommended that creatinine clearance be calculated in all patients prior to initiating therapy and as clinically appropriate during therapy with VIREAD. Routine monitoring of calculated creatinine clearance and serum phosphorus should be performed in patients at risk for renal impairment. Dosing interval adjustment of VIREAD and close monitoring of renal function are recommended in all patients with creatinine clearance <50 mL/min [See Dosage and Administration (2.2) ] . No safety or efficacy data are available in patients with renal impairment who received VIREAD using these dosing guidelines, so the potential benefit of VIREAD therapy should be assessed against the potential risk of renal toxicity. VIREAD should be avoided with concurrent or recent use of a nephrotoxic agent. 5.4 Coadministration with Other Products VIREAD should not be used in combination with the fixed-dose combination products TRUVADA or ATRIPLA since tenofovir disoproxil fumarate is a component of these products. VIREAD should not be administered in combination with HEPSERA ® (adefovir dipivoxil) [See Drug Interactions (7.4) ]. 5.5 Patients Coinfected with HIV-1 and HBV Due to the risk of development of HIV-1 resistance, VIREAD should only be used in HIV-1 and HBV coinfected patients as part of an appropriate antiretroviral combination regimen. HIV-1 antibody testing should be offered to all HBV-infected patients before initiating therapy with VIREAD. It is also recommended that all patients with HIV-1 be tested for the presence of chronic hepatitis B before initiating treatment with VIREAD. 5.6 Decreases in Bone Mineral Density Bone mineral density (BMD) monitoring should be considered for patients who have a history of pathologic bone fracture or are at risk for osteopenia. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial for all patients. If bone abnormalities are suspected then appropriate consultation should be obtained. In HIV-infected patients treated with VIREAD in Study 903 through 144 weeks, decreases from baseline in BMD were seen at the lumbar spine and hip in both arms of the study. At Week 144, there was a significantly greater mean percentage decrease from baseline in BMD at the lumbar spine in patients receiving VIREAD + lamivudine + efavirenz (-2.2% ± 3.9) compared with patients receiving stavudine + lamivudine + efavirenz (-1.0% ± 4.6). Changes in BMD at the hip were similar between the two treatment groups (-2.8% ± 3.5 in the VIREAD group vs. -2.4% ± 4.5 in the stavudine group). In both groups, the majority of the reduction in BMD occurred in the first 24–48 weeks of the study and this reduction was sustained through Week 144. Twenty-eight percent of VIREAD-treated patients vs. 21% of the stavudine-treated patients lost at least 5% of BMD at the spine or 7% of BMD at the hip. Clinically relevant fractures (excluding fingers and toes) were reported in 4 patients in the VIREAD group and 6 patients in the stavudine group. In addition, there were significant increases in biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C-telopeptide, and urinary N-telopeptide) in the VIREAD group relative to the stavudine group, suggesting increased bone turnover. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in the VIREAD group. Except for bone specific alkaline phosphatase, these changes resulted in values that remained within the normal range. The effects of VIREAD-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of VIREAD [See Adverse Reactions (6.2) ] . The bone effects of VIREAD have not been studied in patients with chronic HBV infection. 5.7 Fat Redistribution In HIV-infected patients 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 combination antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established. 5.8 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in HIV-infected patients treated with combination antiretroviral therapy, including VIREAD. 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. 5.9 Early Virologic Failure Clinical studies in HIV-infected patients have demonstrated that certain regimens that only contain three nucleoside reverse transcriptase inhibitors (NRTI) are generally less effective than triple drug regimens containing two NRTIs in combination with either a non-nucleoside reverse transcriptase inhibitor or a HIV-1 protease inhibitor. In particular, early virological failure and high rates of resistance substitutions have been reported. Triple nucleoside regimens should therefore be used with caution. Patients on a therapy utilizing a triple nucleoside-only regimen should be carefully monitored and considered for treatment modification.

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 Exacerbation of Hepatitis [See Boxed Warning , Warnings and Precautions (5.2) ] . New Onset or Worsening Renal Impairment [See Warnings and Precautions (5.3) ] . Decreases in Bone Mineral Density [See Warnings and Precautions (5.6) ] . Immune Reconstitution Syndrome [See Warnings and Precautions (5.8) ] . In HIV-infected patients: Most common adverse reactions (incidence ≥10%, Grades 2 – 4) are rash, diarrhea, headache, pain, depression, asthenia, and nausea. ( 6 ) In HBV-infected patients: Most common adverse reaction (all grades) was nausea (9%). ( 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 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. Clinical Trials in Patients with HIV Infection More than 12,000 patients have been treated with VIREAD alone or in combination with other antiretroviral medicinal products for periods of 28 days to 215 weeks in clinical trials and expanded access studies. A total of 1,544 patients have received VIREAD 300 mg once daily in clinical trials; over 11,000 patients have received VIREAD in expanded access studies. The most common adverse reactions (incidence ≥10%, Grades 2–4) identified from any of the 3 large controlled clinical trials include rash, diarrhea, headache, pain, depression, asthenia, and nausea. Treatment-Naïve Patients Study 903 - Treatment-Emergent Adverse Reactions: The most common adverse reactions seen in a double-blind comparative controlled study in which 600 treatment-naïve patients received VIREAD (N=299) or stavudine (N=301) in combination with lamivudine and efavirenz for 144 weeks (Study 903) were mild to moderate gastrointestinal events and dizziness. Mild adverse reactions (Grade 1) were common with a similar incidence in both arms, and included dizziness, diarrhea, and nausea. Selected treatment-emergent moderate to severe adverse reactions are summarized in Table 2. Table 2 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 903 (0–144 Weeks) VIREAD + 3TC + EFV d4T + 3TC + EFV N=299 N=301 Body as a Whole Headache 14% 17% Pain 13% 12% Fever 8% 7% Abdominal pain 7% 12% Back pain 9% 8% Asthenia 6% 7% Digestive System Diarrhea 11% 13% Nausea 8% 9% Dyspepsia 4% 5% Vomiting 5% 9% Metabolic Disorders Lipodystrophy Lipodystrophy represents a variety of investigator-described adverse events not a protocol-defined syndrome. 1% 8% Musculoskeletal Arthralgia 5% 7% Myalgia 3% 5% Nervous System Depression 11% 10% Insomnia 5% 8% Dizziness 3% 6% Peripheral neuropathy Peripheral neuropathy includes peripheral neuritis and neuropathy. 1% 5% Anxiety 6% 6% Respiratory Pneumonia 5% 5% Skin and Appendages Rash event Rash event includes rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, and pustular rash. 18% 12% Laboratory Abnormalities: With the exception of fasting cholesterol and fasting triglyceride elevations that were more common in the stavudine group (40% and 9%) compared with VIREAD (19% and 1%) respectively, laboratory abnormalities observed in this study occurred with similar frequency in the VIREAD and stavudine treatment arms. A summary of Grade 3 and 4 laboratory abnormalities is provided in Table 3. Table 3 Grade 3/4 Laboratory Abnormalities Reported in ≥1% of VIREAD-Treated Patients in Study 903 (0–144 Weeks) VIREAD + 3TC + EFV d4T + 3TC + EFV N=299 N=301 Any ≥ Grade 3 Laboratory Abnormality 36% 42% Fasting Cholesterol (>240 mg/dL) 19% 40% Creatine Kinase (M: >990 U/L) (F: >845 U/L) 12% 12% Serum Amylase (>175 U/L) 9% 8% AST (M: >180 U/L) (F: >170 U/L) 5% 7% ALT (M: >215 U/L) (F: >170 U/L) 4% 5% Hematuria (>100 RBC/HPF) 7% 7% Neutrophils (<750/mm 3 ) 3% 1% Fasting Triglycerides (>750 mg/dL) 1% 9% Study 934 - Treatment Emergent Adverse Reactions: In Study 934, 511 antiretroviral-naïve patients 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 study were generally consistent with those seen in previous studies in treatment-experienced or treatment-naïve patients (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) VIREAD From Weeks 96 to 144 of the study, patients received TRUVADA with efavirenz in place of VIREAD + EMTRIVA with efavirenz. + FTC + 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% Laboratory Abnormalities: Laboratory abnormalities observed in this study were generally consistent with those seen in previous studies (Table 5). Table 5 Significant Laboratory Abnormalities Reported in ≥1% of Patients in Any Treatment Group in Study 934 (0–144 Weeks) VIREAD From Weeks 96 to 144 of the study, patients received TRUVADA with efavirenz in place of VIREAD + EMTRIVA with efavirenz. + FTC + 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% Treatment-Experienced Patients Treatment-Emergent Adverse Reactions: The adverse reactions seen in treatment experienced patients were generally consistent with those seen in treatment naïve patients including mild to moderate gastrointestinal events, such as nausea, diarrhea, vomiting, and flatulence. Less than 1% of patients discontinued participation in the clinical studies due to gastrointestinal adverse reactions (Study 907). A summary of moderate to severe, treatment-emergent adverse reactions that occurred during the first 48 weeks of Study 907 is provided in Table 6. Table 6 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 ≥3% in Any Treatment Group in Study 907 (0–48 Weeks) VIREAD (N=368) (Week 0–24) Placebo (N=182) (Week 0–24) VIREAD (N=368) (Week 0–48) Placebo Crossover to VIREAD (N=170) (Week 24–48) Body as a Whole Asthenia 7% 6% 11% 1% Pain 7% 7% 12% 4% Headache 5% 5% 8% 2% Abdominal pain 4% 3% 7% 6% Back pain 3% 3% 4% 2% Chest pain 3% 1% 3% 2% Fever 2% 2% 4% 2% Digestive System Diarrhea 11% 10% 16% 11% Nausea 8% 5% 11% 7% Vomiting 4% 1% 7% 5% Anorexia 3% 2% 4% 1% Dyspepsia 3% 2% 4% 2% Flatulence 3% 1% 4% 1% Respiratory Pneumonia 2% 0% 3% 2% Nervous System Depression 4% 3% 8% 4% Insomnia 3% 2% 4% 4% Peripheral neuropathy Peripheral neuropathy includes peripheral neuritis and neuropathy. 3% 3% 5% 2% Dizziness 1% 3% 3% 1% Skin and Appendage Rash event Rash event includes rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, and pustular rash. 5% 4% 7% 1% Sweating 3% 2% 3% 1% Musculoskeletal Myalgia 3% 3% 4% 1% Metabolic Weight loss 2% 1% 4% 2% Laboratory Abnormalities: Laboratory abnormalities observed in this study occurred with similar frequency in the VIREAD and placebo-treated groups. A summary of Grade 3 and 4 laboratory abnormalities is provided in Table 7. Table 7 Grade 3/4 Laboratory Abnormalities Reported in ≥1% of VIREAD-Treated Patients in Study 907 (0–48 Weeks) VIREAD (N=368) (Week 0–24) Placebo (N=182) (Week 0–24) VIREAD (N=368) (Week 0–48) Placebo Crossover to VIREAD (N=170) (Week 24–48) Any ≥ Grade 3 Laboratory Abnormality 25% 38% 35% 34% Triglycerides (>750 mg/dL) 8% 13% 11% 9% Creatine Kinase (M: >990U/L) (F: >845 U/L) 7% 14% 12% 12% Serum Amylase (>175 U/L) 6% 7% 7% 6% Glycosuria (≥3+) 3% 3% 3% 2% AST (M: >180 U/L) (F: >170 U/L) 3% 3% 4% 5% ALT (M: >215 U/L) (F: >170 U/L) 2% 2% 4% 5% Serum Glucose (>250 U/L) 2% 4% 3% 3% Neutrophils (<750/mm 3 ) 1% 1% 2% 1% Clinical Trials in Patients with Chronic Hepatitis B Treatment-Emergent Adverse Reactions: In controlled clinical trials in patients with chronic hepatitis B, more patients treated with VIREAD experienced nausea: 9% with VIREAD versus 2% with HEPSERA. Other treatment-emergent adverse reactions reported in >5% of patients treated with VIREAD included: abdominal pain, diarrhea, headache, dizziness, fatigue, nasopharyngitis, back pain and skin rash. Laboratory Abnormalities: A summary of Grade 3 and 4 laboratory abnormalities is provided in Table 8. Table 8. Grade 3/4 Laboratory Abnormalities Reported in ≥1% of VIREAD-Treated Patients in Studies 0102 and 0103 (0-48 Weeks) VIREAD (N=426) HEPSERA (N=215) Any ≥ Grade 3 Laboratory Abnormality 19% 13% Creatine Kinase (M: >990U/L) (F: >845 U/L) 2% 3% Serum Amylase (>175 U/L) 4% 1% Glycosuria (≥3+) 3% <1% AST (M: >180 U/L) (F: >170 U/L) 4% 4% ALT (M: >215 U/L) (F: >170 U/L) 10% 6% The overall incidence of on-treatment ALT elevations (defined as serum ALT >2 × baseline and >10 × ULN, with or without associated symptoms) was similar between VIREAD (2.6%) and HEPSERA (2%). ALT elevations generally occurred within the first 4–8 weeks of treatment and were accompanied by decreases in HBV DNA levels. No patient had evidence of decompensation. ALT flares typically resolved within 4 to 8 weeks without changes in study medication. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of VIREAD. Because postmarketing 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. Immune System Disorders allergic reaction Metabolism and Nutrition Disorders lactic acidosis, hypokalemia, hypophosphatemia Respiratory, Thoracic , and Mediastinal Disorders dyspnea Gastrointestinal Disorders pancreatitis, increased amylase, abdominal pain Hepatobiliary Disorders hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT gamma GT) Skin and Subcutaneous Tissue Disorders rash Musculoskeletal and Connective Tissue Disorders rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy Renal and Urinary Disorders acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria General Disorders and Administration Site Conditions asthenia The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, hypophosphatemia.

<table ID="table2" width="80%"> <caption>Table 2 Selected Treatment-Emergent Adverse Reactions<footnote>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 903 (0&#x2013;144 Weeks)</caption> <col align="left" valign="middle" width="34%"/> <col align="center" valign="middle" width="33%"/> <col align="center" valign="middle" width="33%"/> <thead> <tr> <th styleCode="Lrule Rrule"/> <th styleCode="Rrule Botrule">VIREAD + 3TC + EFV</th> <th styleCode="Rrule Botrule">d4T + 3TC + EFV</th> </tr> <tr> <th styleCode="Lrule Rrule"/> <th styleCode="Rrule">N=299</th> <th styleCode="Rrule">N=301</th> </tr> </thead> <tbody> <tr> <td styleCode="Lrule">Body as a Whole</td> <td styleCode="Lrule Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule"> Headache</td> <td styleCode="Lrule Rrule">14%</td> <td styleCode="Rrule">17%</td> </tr> <tr> <td styleCode="Lrule"> Pain</td> <td styleCode="Lrule Rrule">13%</td> <td styleCode="Rrule">12%</td> </tr> <tr> <td styleCode="Lrule"> Fever</td> <td styleCode="Lrule Rrule">8%</td> <td styleCode="Rrule">7%</td> </tr> <tr> <td styleCode="Lrule"> Abdominal pain</td> <td styleCode="Lrule Rrule">7%</td> <td styleCode="Rrule">12%</td> </tr> <tr> <td styleCode="Lrule"> Back pain</td> <td styleCode="Lrule Rrule">9%</td> <td styleCode="Rrule">8%</td> </tr> <tr> <td styleCode="Lrule"> Asthenia</td> <td styleCode="Lrule Rrule">6%</td> <td styleCode="Rrule">7%</td> </tr> <tr> <td styleCode="Lrule Toprule">Digestive System</td> <td styleCode="Lrule Rrule Toprule"/> <td styleCode="Rrule Toprule"/> </tr> <tr> <td styleCode="Lrule"> Diarrhea</td> <td styleCode="Lrule Rrule">11%</td> <td styleCode="Rrule">13%</td> </tr> <tr> <td styleCode="Lrule"> Nausea</td> <td styleCode="Lrule Rrule">8%</td> <td styleCode="Rrule">9%</td> </tr> <tr> <td styleCode="Lrule"> Dyspepsia</td> <td styleCode="Lrule Rrule">4%</td> <td styleCode="Rrule">5%</td> </tr> <tr> <td styleCode="Lrule"> Vomiting</td> <td styleCode="Lrule Rrule">5%</td> <td styleCode="Rrule">9%</td> </tr> <tr> <td styleCode="Lrule Toprule">Metabolic Disorders</td> <td styleCode="Lrule Rrule Toprule"/> <td styleCode="Rrule Toprule"/> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Lipodystrophy<footnote>Lipodystrophy represents a variety of investigator-described adverse events not a protocol-defined syndrome.</footnote> </td> <td styleCode="Lrule Rrule">1%</td> <td styleCode="Rrule">8%</td> </tr> <tr> <td styleCode="Lrule">Musculoskeletal</td> <td styleCode="Lrule Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule"> Arthralgia</td> <td styleCode="Lrule Rrule">5%</td> <td styleCode="Rrule">7%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Myalgia</td> <td styleCode="Lrule Rrule">3%</td> <td styleCode="Rrule">5%</td> </tr> <tr> <td styleCode="Lrule">Nervous System</td> <td styleCode="Lrule Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule"> Depression</td> <td styleCode="Lrule Rrule">11%</td> <td styleCode="Rrule">10%</td> </tr> <tr> <td styleCode="Lrule"> Insomnia</td> <td styleCode="Lrule Rrule">5%</td> <td styleCode="Rrule">8%</td> </tr> <tr> <td styleCode="Lrule"> Dizziness</td> <td styleCode="Lrule Rrule">3%</td> <td styleCode="Rrule">6%</td> </tr> <tr> <td styleCode="Lrule"> Peripheral neuropathy<footnote>Peripheral neuropathy includes peripheral neuritis and neuropathy.</footnote> </td> <td styleCode="Lrule Rrule">1%</td> <td styleCode="Rrule">5%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Anxiety</td> <td styleCode="Lrule Rrule">6%</td> <td styleCode="Rrule">6%</td> </tr> <tr> <td styleCode="Lrule">Respiratory</td> <td styleCode="Lrule Rrule"/> <td styleCode="Rrule"/> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule"> Pneumonia</td> <td styleCode="Lrule Rrule">5%</td> <td styleCode="Rrule">5%</td> </tr> <tr> <td styleCode="Lrule">Skin and Appendages</td> <td styleCode="Lrule Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule"> Rash event<footnote>Rash event includes rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, and pustular rash.</footnote> </td> <td styleCode="Lrule Rrule">18%</td> <td styleCode="Rrule">12%</td> </tr> </tbody> </table>

<table ID="table3" width="80%"> <caption>Table 3 Grade 3/4 Laboratory Abnormalities Reported in &#x2265;1% of VIREAD-Treated Patients in Study 903 (0&#x2013;144 Weeks)</caption> <col align="left" valign="middle" width="34%"/> <col align="center" valign="middle" width="33%"/> <col align="center" valign="middle" width="33%"/> <thead> <tr> <th styleCode="Lrule Rrule"/> <th styleCode="Rrule Botrule">VIREAD + 3TC + EFV</th> <th styleCode="Rrule Botrule">d4T + 3TC + EFV</th> </tr> <tr> <th styleCode="Lrule Rrule"/> <th styleCode="Rrule">N=299</th> <th styleCode="Rrule">N=301</th> </tr> </thead> <tbody> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Any &#x2265; Grade 3 Laboratory Abnormality</td> <td styleCode="Rrule">36%</td> <td styleCode="Rrule">42%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Fasting Cholesterol (&gt;240 mg/dL)</td> <td styleCode="Rrule">19%</td> <td styleCode="Rrule">40%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Creatine Kinase (M: &gt;990 U/L) (F: &gt;845 U/L)</td> <td styleCode="Rrule">12%</td> <td styleCode="Rrule">12%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Serum Amylase (&gt;175 U/L)</td> <td styleCode="Rrule">9%</td> <td styleCode="Rrule">8%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">AST (M: &gt;180 U/L) (F: &gt;170 U/L)</td> <td styleCode="Rrule">5%</td> <td styleCode="Rrule">7%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">ALT (M: &gt;215 U/L) (F: &gt;170 U/L)</td> <td styleCode="Rrule">4%</td> <td styleCode="Rrule">5%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Hematuria (&gt;100 RBC/HPF)</td> <td styleCode="Rrule">7%</td> <td styleCode="Rrule">7%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Neutrophils (&lt;750/mm³)</td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">1%</td> </tr> <tr> <td styleCode="Lrule Rrule">Fasting Triglycerides (&gt;750 mg/dL)</td> <td styleCode="Rrule">1%</td> <td styleCode="Rrule">9%</td> </tr> </tbody> </table>

<table ID="table4" width="80%"> <caption>Table 4 Selected Treatment-Emergent Adverse Reactions<footnote>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">VIREAD<footnote>From Weeks 96 to 144 of the study, patients received TRUVADA with efavirenz in place of VIREAD + EMTRIVA with efavirenz.</footnote> + FTC + 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> <td styleCode="Lrule"> Dizziness</td> <td styleCode="Lrule Rrule">8%</td> <td styleCode="Rrule">7%</td> </tr> <tr> <td styleCode="Lrule Toprule">Psychiatric Disorders</td> <td styleCode="Lrule Rrule Toprule"/> <td styleCode="Rrule Toprule"/> </tr> <tr> <td styleCode="Lrule"> Depression</td> <td styleCode="Lrule Rrule">9%</td> <td styleCode="Rrule">7%</td> </tr> <tr> <td styleCode="Lrule"> Insomnia</td> <td styleCode="Lrule Rrule">5%</td> <td styleCode="Rrule">7%</td> </tr> <tr> <td styleCode="Lrule Toprule">Skin and Subcutaneous Tissue Disorders</td> <td styleCode="Lrule Rrule Toprule"/> <td styleCode="Rrule Toprule"/> </tr> <tr> <td styleCode="Lrule"> Rash event<footnote>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>