FDA label ac228abb-ea52-4688-a175-8ad02b651fa0

WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate, a component of STRIBILD, in combination with other antiretrovirals [see Warnings and Precautions (5.1) ] . STRIBILD is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of STRIBILD have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and human immunodeficiency virus-1 (HIV-1) and have discontinued EMTRIVA or VIREAD, which are components of STRIBILD. 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 STRIBILD. 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 ACUTE 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, including tenofovir disoproxil fumarate (DF), a component of STRIBILD. ( 5.1 ) STRIBILD is not approved for the treatment of chronic hepatitis B virus (HBV) infection. Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HIV-1 and HBV who have discontinued EMTRIVA or VIREAD, two of the components of STRIBILD. Hepatic function should be monitored closely in these patients. If appropriate, initiation of anti-hepatitis B therapy may be warranted. ( 5.2 )

New onset or worsening renal impairment: Can include acute renal failure and Fanconi syndrome. Assess creatinine clearance (CLcr), urine glucose and urine protein before initiating treatment with STRIBILD. Monitor CLcr, urine glucose, and urine protein in all patients. Monitor serum phosphorus in patients at risk for renal impairment. Avoid administering STRIBILD with concurrent or recent use of nephrotoxic drugs. ( 5.3 ) Avoid coadministration with other anti-retroviral products: Do not use with drugs containing emtricitabine or tenofovir disoproxil fumarate including ATRIPLA, COMPLERA, EMTRIVA, TRUVADA, or VIREAD; with drugs containing lamivudine; or with drugs or regimens containing ritonavir. Do not administer in combination with HEPSERA. ( 5.4 ) Decreases in bone mineral density (BMD): Consider monitoring BMD in patients with a history of pathologic fracture or other risk factors of osteoporosis or bone loss. ( 5.5 ) Redistribution/accumulation of body fat: Observed in patients receiving antiretroviral therapy. ( 5.6 ) Immune reconstitution syndrome: May necessitate further evaluation and treatment. ( 5.7 ) 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 tenofovir DF, a component of STRIBILD, 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 STRIBILD 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. STRIBILD is not approved for the treatment of chronic HBV infection and the safety and efficacy of STRIBILD have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued emtricitabine or tenofovir DF, two of the components of STRIBILD. In some patients infected with HBV and treated with EMTRIVA, the exacerbations of hepatitis B were associated with liver decompensation and liver failure. Patients who are coinfected with HIV-1 and HBV should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with STRIBILD. If appropriate, initiation of anti-hepatitis B therapy may be warranted. 5.3 New Onset or Worsening Renal Impairment Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir DF, a component of STRIBILD, and with the use of STRIBILD [see Adverse Reactions (6.2) ] . In the clinical trials of STRIBILD over 96 weeks, 10 (1.4%) subjects in the STRIBILD group (N=701) and 2 (0.3%) subjects in the combined comparator groups (N = 707) discontinued study drug due to a renal adverse reaction. Of these discontinuations, 8 in the STRIBILD group and 1 in the combined comparator groups occurred during the first 48 week. Four (0.6%) of the subjects who received STRIBILD developed laboratory findings consistent with proximal renal tubular dysfunction leading to discontinuation of STRIBILD compared to none in the comparator groups. Two of these four subjects had renal impairment (i.e. estimated creatinine clearance less than 70 mL per minute) at baseline. The laboratory findings in these 4 subjects with evidence of proximal tubulopathy improved but did not completely resolve in all subjects upon discontinuation of STRIBILD. Renal replacement therapy was not required for these subjects. Estimated creatinine clearance, urine glucose and urine protein should be documented in all patients prior to initiating therapy. Initiation of STRIBILD in patients with estimated creatinine clearance below 70 mL per minute is not recommended. STRIBILD should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs (NSAIDs)) [see Drug Interactions (7.4) ] . Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir DF. Some patients required hospitalization and renal replacement therapy. Alternatives to NSAIDs should be considered, if needed, in patients at risk for renal dysfunction. Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in at-risk patients. Routine monitoring of estimated creatinine clearance, urine glucose, and urine protein should be performed during STRIBILD therapy in all patients. Additionally, serum phosphorus should be measured in patients at risk for renal impairment. Although cobicistat (a component of STRIBILD) may cause modest increases in serum creatinine and modest declines in estimated creatinine clearance without affecting renal glomerular function [see Adverse Reactions (6.1) ] , patients who experience a confirmed increase in serum creatinine of greater than 0.4 mg per dL from baseline should be closely monitored for renal safety. The emtricitabine and tenofovir DF components of STRIBILD are primarily excreted by the kidney. STRIBILD should be discontinued if estimated creatinine clearance declines below 50 mL per minute as dose interval adjustment required for emtricitabine and tenofovir DF cannot be achieved with the fixed-dose combination tablet. 5.4 Avoid Use with Other Antiretroviral Products STRIBILD is indicated for use as a complete regimen for the treatment of HIV-1 infection and coadministration with other antiretroviral products is not recommended. STRIBILD is not recommended for coadministration with the following: emtricitabine or tenofovir DF (ATRIPLA, COMPLERA, EMTRIVA, TRUVADA, VIREAD); products containing lamivudine (COMBIVIR, EPIVIR, EPIVIR-HBV, EPZICOM, TRIZIVIR) or adefovir dipivoxil (HEPSERA); ritonavir (NORVIR, KALETRA). 5.5 Bone Effects of Tenofovir DF Bone Mineral Density: In clinical trials in HIV-1 infected adults, tenofovir DF (a component of STRIBILD) was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators. Serum parathyroid hormone levels and 1.25 Vitamin D levels were also higher in subjects receiving tenofovir DF. For additional information, see Adverse Reactions (6.1) and consult the VIREAD prescribing information. The effects of tenofovir DF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown. Assessment of BMD should be considered for HIV-1 infected patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial in all patients. If bone abnormalities are suspected, then appropriate consultation should be obtained. Mineralization Defects: Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with the use of tenofovir DF [see Adverse Reactions (6.2) ] . Arthralgias and muscle pain or weakness have also been reported in cases of proximal renal tubulopathy. Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms while receiving products containing tenofovir DF [see Warnings and Precautions (5.3) ] . 5.6 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. 5.7 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including STRIBILD. 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 drug 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) ] . New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.3) ] . Bone Effects of Tenofovir DF [see Warnings and Precautions (5.5) ] . Immune Reconstitution Syndrome [see Warnings and Precautions (5.7) ] . Most common adverse drug reactions to STRIBILD (incidence greater than or equal to 10%, all grades) are nausea and 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 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. The safety assessment of STRIBILD is based on the Week 96 pooled data from 1408 subjects in two randomized, double-blind, active-controlled clinical trials, Study 102 and Study 103, in antiretroviral treatment-naïve HIV-1 infected adult subjects [see Clinical Studies (14) ]. A total of 701 subjects received STRIBILD once daily for at least 96 weeks. The proportion of subjects who discontinued treatment with STRIBILD (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir DF 300 mg); ATRIPLA (efavirenz 600 mg/emtricitabine 200 mg/tenofovir DF 300 mg); or atazanavir (ATV) + ritonavir (RTV) + TRUVADA (emtricitabine 200 mg/tenofovir DF 300 mg) due to adverse events, regardless of severity, was 4.6%, 6.8% and 5.9%, respectively. Table 2 displays the frequency of adverse drug reactions greater than or equal to 5% of subjects in any treatment arm. Table 2 Adverse Drug Reactions Frequencies of adverse reactions are based on all treatment-emergent adverse events, attributed to study drugs. (all grades) Reported in ≥ 5% of Subjects in Any Treatment Arm in Studies 102 and 103 (Week 96 analysis). STRIBILD N=701 ATRIPLA N=352 ATV + RTV + TRUVADA N=355 EYE DISORDERS Ocular icterus <1% 0% 13% GASTROINTESTINAL DISORDERS Diarrhea 12% 11% 17% Flatulence 2% <1% 8% Nausea 16% 9% 14% GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS Fatigue 4% 8% 6% HEPATOBILIARY DISORDERS Jaundice 0% <1% 9% NERVOUS SYSTEM DISORDERS Somnolence 1% 7% 1% Headache 7% 4% 6% Dizziness 3% 21% 4% PSYCHIATRIC DISORDERS Insomnia 3% 8% 1% Abnormal dreams 9% 26% 4% SKIN AND SUBCUTANEOUS TISSUE DISORDERS Rash Rash event includes dermatitis, drug eruption, eczema, pruritus, pruritus generalized, rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic, and urticaria. 3% 15% 6% See Warnings and Precautions (5.3) , for a discussion of renal adverse reactions from clinical trials experience with STRIBILD. Adverse Reactions from Clinical Trials of the Components of STRIBILD Emtricitabine and Tenofovir Disoproxil Fumarate: In addition to the adverse reactions observed with STRIBILD, the following adverse reactions occurred in at least 5% of treatment-experienced or treatment-naïve subjects receiving emtricitabine or tenofovir DF with other antiretroviral agents in other clinical trials: depression, abdominal pain, dyspepsia, vomiting, fever, pain, nasopharyngitis, pneumonia, sinusitis, upper respiratory tract infection, arthralgia, back pain, myalgia, paresthesia, peripheral neuropathy (including peripheral neuritis and neuropathy), anxiety, increased cough, and rhinitis. Skin discoloration has been reported with higher frequency among emtricitabine-treated subjects; it was manifested by hyperpigmentation on the palms and/or soles and was generally mild and asymptomatic. The mechanism and clinical significance are unknown. Laboratory Abnormalities The frequency of laboratory abnormalities (Grades 3–4) occurring in at least 2% of subjects receiving STRIBILD in Studies 102 and 103 are presented in Table 3. Table 3 Laboratory Abnormalities (Grades 3–4) Reported in ≥ 2% of Subjects Receiving STRIBILD in Studies 102 and 103 (Week 96 analysis) STRIBILD ATRIPLA ATV + RTV + TRUVADA Laboratory Parameter Abnormality Frequencies are based on treatment-emergent laboratory abnormalities. , For subjects with serum amylase > 1.5 × upper limit of normal, lipase test was also performed. The frequency of increased lipase (Grades 3–4) occurring in STRIBILD (N=61), ATRIPLA (N=36), and ATV +RTV + TRUVADA (N=36) was 15%, 17%, and 25%, respectively. N=701 N=352 N=355 AST (>5.0 × ULN) 2% 6% 6% Amylase (>2.0 × ULN) 3% 2% 4% Creatine Kinase (≥ 10.0 × ULN) 7% 14% 10% Urine RBC (Hematuria) (> 75 RBC/HPF) 3% 2% 4% In Study 103, BMD was assessed by DEXA in a non-random subset of 120 subjects. Mean percentage decreases in BMD from baseline to Week 96 in the STRIBILD group (N = 47) were comparable to the ATV + RTV + TRUVADA group (N = 53) at the lumbar spine (-2.0% versus -3.5%, respectively) and at the hip (-3.2% versus -4.2%, respectively). In Studies 102 and 103, bone fractures occurred in 14 subjects (2.0%) in the STRIBILD group, 8 subjects (2.3%) in the ATRIPLA group, and 14 subjects (3.9%) in the ATV + RTV + TRUVADA group. These findings were consistent with data from an earlier 144-week trial of treatment-naïve subjects receiving tenofovir DF + lamivudine + efavirenz. Proteinuria (all grades) occurred in 46% of subjects receiving STRIBILD, 38% of subjects receiving ATRIPLA, and 37% of subjects receiving ATV + RTV + TRUVADA. The cobicistat component of STRIBILD has been shown to increase serum creatinine and decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting renal glomerular function. In Studies 102 and 103, increases in serum creatinine and decreases in estimated creatinine clearance occurred early in treatment with STRIBILD, after which they stabilized. Table 4 displays the mean changes in serum creatinine and eGFR levels at Week 96 and the percentage of subjects with elevations in serum creatinine (All Grades). Table 4 Change from Baseline in Serum Creatinine and eGFR and Incidence of Elevated Serum Creatinine (All Grades) at Week 96 STRIBILD (N=701) ATRIPLA (N=352) ATV + RTV + TRUVADA (N=355) Serum Creatinine (mg/dL) Mean change ±SD 0.13 (±0.13) 0.01 (±0.13) 0.08 (±0.14) eGFR by Cockcroft-Gault (mL/min) -13.2 (±15.7) -0.9 (±16.1) -8.6 (±17.8) Subjects with Elevations in Serum Creatinine (All Grades)(%) 10 1 5 Emtricitabine or Tenofovir DF: In addition to the laboratory abnormalities observed with STRIBILD, the following laboratory abnormalities have been previously reported in subjects treated with emtricitabine or tenofovir DF with other antiretroviral agents in other clinical trials: Grade 3 or 4 laboratory abnormalities of ALT (M: greater than 215 U per L; F: greater than 170 U per L), alkaline phosphatase (greater than 550 U per L), bilirubin (greater than 2.5 × ULN), serum glucose (less than 40 or greater than 250 mg per dL), glycosuria (greater than or equal to 3+), neutrophils (less than 750 per mm 3 ), fasting cholesterol (greater than 240 mg per dL), and fasting triglycerides (greater than 750 mg per dL). Serum Lipids: In the clinical trials of STRIBILD, a similar percentage of subjects receiving STRIBILD, ATRIPLA, and ATV + RTV + TRUVADA were on lipid lowering agents at baseline (11%, 11%, and 12%, respectively). While receiving study drug through Week 96, an additional 8% of STRIBILD subjects were started on lipid lowering agents, compared to 9% of ATRIPLA and 8% of ATV + RTV + TRUVADA subjects. Changes from baseline in total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides are presented in Table 5. Table 5 Lipid Values, Mean Change from Baseline, Reported in Subjects Receiving STRIBILD or Comparator in Studies 102 and 103 STRIBILD N=701 ATRIPLA N=352 ATV + RTV + TRUVADA N=355 Baseline Week 96 Baseline Week 96 Baseline Week 96 mg/dL Change The change from baseline is the mean of within-patient changes from baseline for patients with both baseline and Week 96 values. mg/dL Change mg/dL Change Total Cholesterol (fasted) 166 [N=675] +12 [N=571] 161 [N=343] +20 [N=288] 168 [N=337] +11 [N=279] HDL-cholesterol (fasted) 43 [N=675] +7 [N=571] 43 [N=343] +9 [N=288] 42 [N=335] +6 [N=278] LDL-cholesterol (fasted) 100 [N=675] +12 [N=572] 97 [N=343] +17 [N=287] 101 [N=337] +13 [N=280] Triglycerides (fasted) 122 [N=675] +8 [N=571] 121 [N=343] +17 [N=288] 132 [N=337] +25 [N=279] 6.2 Postmarketing Experience 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. The following adverse reactions have been identified during post approval use of tenofovir DF. No additional postmarketing adverse reactions specific for emtricitabine have been identified. Immune System Disorders allergic reaction, including angioedema 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 width="80%"> <caption>Table 2 Adverse Drug Reactions<footnote>Frequencies of adverse reactions are based on all treatment-emergent adverse events, attributed to study drugs.</footnote> (all grades) Reported in &#x2265; 5% of Subjects in Any Treatment Arm in Studies 102 and 103 (Week 96 analysis).</caption> <col width="49%" align="left" valign="top"/> <col width="17%" align="center" valign="top"/> <col width="17%" align="center" valign="top"/> <col width="17%" align="center" valign="top"/> <thead> <tr valign="bottom"> <th styleCode="Lrule Rrule"/> <th styleCode="Rrule">STRIBILD N=701</th> <th styleCode="Rrule">ATRIPLA N=352</th> <th styleCode="Rrule">ATV + RTV + TRUVADA N=355</th> </tr> </thead> <tbody> <tr> <td styleCode="Lrule Rrule">EYE DISORDERS</td> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Ocular icterus</td> <td styleCode="Rrule">&lt;1%</td> <td styleCode="Rrule">0%</td> <td styleCode="Rrule">13%</td> </tr> <tr> <td styleCode="Lrule Rrule">GASTROINTESTINAL DISORDERS</td> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule Rrule"> Diarrhea</td> <td styleCode="Rrule">12%</td> <td styleCode="Rrule">11%</td> <td styleCode="Rrule">17%</td> </tr> <tr> <td styleCode="Lrule Rrule"> Flatulence</td> <td styleCode="Rrule">2%</td> <td styleCode="Rrule">&lt;1%</td> <td styleCode="Rrule">8%</td> </tr> <tr> <td styleCode="Lrule Rrule"> Nausea</td> <td styleCode="Rrule">16%</td> <td styleCode="Rrule">9%</td> <td styleCode="Rrule">14%</td> </tr> <tr> <td styleCode="Lrule Rrule Toprule">GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS</td> <td styleCode="Rrule Toprule"/> <td styleCode="Rrule Toprule"/> <td styleCode="Rrule Toprule"/> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Fatigue</td> <td styleCode="Rrule">4%</td> <td styleCode="Rrule">8%</td> <td styleCode="Rrule">6%</td> </tr> <tr> <td styleCode="Lrule Rrule">HEPATOBILIARY DISORDERS</td> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Jaundice</td> <td styleCode="Rrule">0%</td> <td styleCode="Rrule">&lt;1%</td> <td styleCode="Rrule">9%</td> </tr> <tr> <td styleCode="Lrule Rrule">NERVOUS SYSTEM DISORDERS</td> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule Rrule"> Somnolence</td> <td styleCode="Rrule">1%</td> <td styleCode="Rrule">7%</td> <td styleCode="Rrule">1%</td> </tr> <tr> <td styleCode="Lrule Rrule"> Headache</td> <td styleCode="Rrule">7%</td> <td styleCode="Rrule">4%</td> <td styleCode="Rrule">6%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Dizziness</td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">21%</td> <td styleCode="Rrule">4%</td> </tr> <tr> <td styleCode="Lrule Rrule">PSYCHIATRIC DISORDERS</td> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule Rrule"> Insomnia</td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">8%</td> <td styleCode="Rrule">1%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> Abnormal dreams</td> <td styleCode="Rrule">9%</td> <td styleCode="Rrule">26%</td> <td styleCode="Rrule">4%</td> </tr> <tr> <td styleCode="Lrule Rrule">SKIN AND SUBCUTANEOUS TISSUE DISORDERS</td> <td styleCode="Rrule"/> <td styleCode="Rrule"/> <td styleCode="Rrule"/> </tr> <tr> <td styleCode="Lrule Rrule"> Rash<footnote>Rash event includes dermatitis, drug eruption, eczema, pruritus, pruritus generalized, rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic, and urticaria.</footnote> </td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">15%</td> <td styleCode="Rrule">6%</td> </tr> </tbody> </table>

<table width="80%" ID="t3"> <caption>Table 3 Laboratory Abnormalities (Grades 3&#x2013;4) Reported in &#x2265; 2% of Subjects Receiving STRIBILD in Studies 102 and 103 (Week 96 analysis)</caption> <col width="43%" align="left" valign="middle"/> <col width="18%" align="center" valign="middle"/> <col width="18%" align="center" valign="middle"/> <col width="21%" align="center" valign="middle"/> <thead> <tr> <th styleCode="Lrule Rrule"/> <th styleCode="Rrule">STRIBILD</th> <th styleCode="Rrule">ATRIPLA</th> <th styleCode="Rrule">ATV + RTV + TRUVADA</th> </tr> </thead> <tbody> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule"> <content styleCode="bold">Laboratory Parameter Abnormality</content> <footnote ID="ft3.1">Frequencies are based on treatment-emergent laboratory abnormalities.</footnote> ^, <footnote>For subjects with serum amylase &gt; 1.5 &#xD7; upper limit of normal, lipase test was also performed. The frequency of increased lipase (Grades 3&#x2013;4) occurring in STRIBILD (N=61), ATRIPLA (N=36), and ATV +RTV + TRUVADA (N=36) was 15%, 17%, and 25%, respectively.</footnote> </td> <td styleCode="Rrule">N=701</td> <td styleCode="Rrule">N=352</td> <td styleCode="Rrule">N=355</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">AST (&gt;5.0 &#xD7; ULN)</td> <td styleCode="Rrule">2%</td> <td styleCode="Rrule">6%</td> <td styleCode="Rrule">6%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Amylase<footnoteRef IDREF="ft3.1"/> (&gt;2.0 &#xD7; ULN)</td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">2%</td> <td styleCode="Rrule">4%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Creatine Kinase (&#x2265; 10.0 &#xD7; ULN)</td> <td styleCode="Rrule">7%</td> <td styleCode="Rrule">14%</td> <td styleCode="Rrule">10%</td> </tr> <tr> <td styleCode="Lrule Rrule">Urine RBC (Hematuria) (&gt; 75 RBC/HPF)</td> <td styleCode="Rrule">3%</td> <td styleCode="Rrule">2%</td> <td styleCode="Rrule">4%</td> </tr> </tbody> </table>

<table width="80%"> <caption>Table 4 Change from Baseline in Serum Creatinine and eGFR and Incidence of Elevated Serum Creatinine (All Grades) at Week 96</caption> <col width="43%" align="left" valign="top"/> <col width="18%" align="center" valign="top"/> <col width="18%" align="center" valign="top"/> <col width="21%" align="center" valign="top"/> <thead> <tr> <th styleCode="Lrule Rrule"/> <th styleCode="Rrule">STRIBILD (N=701)</th> <th styleCode="Rrule">ATRIPLA (N=352)</th> <th styleCode="Rrule">ATV + RTV + TRUVADA (N=355)</th> </tr> </thead> <tbody> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Serum Creatinine (mg/dL)<footnote ID="ft4.1">Mean change &#xB1;SD</footnote> </td> <td styleCode="Rrule">0.13 (&#xB1;0.13)</td> <td styleCode="Rrule">0.01 (&#xB1;0.13)</td> <td styleCode="Rrule">0.08 (&#xB1;0.14)</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">eGFR by Cockcroft-Gault (mL/min)<footnoteRef IDREF="ft4.1"/> </td> <td styleCode="Rrule">-13.2 (&#xB1;15.7)</td> <td styleCode="Rrule">-0.9 (&#xB1;16.1)</td> <td styleCode="Rrule">-8.6 (&#xB1;17.8)</td> </tr> <tr> <td styleCode="Lrule Rrule">Subjects with Elevations in Serum Creatinine (All Grades)(%)</td> <td styleCode="Rrule">10</td> <td styleCode="Rrule">1</td> <td styleCode="Rrule">5</td> </tr> </tbody> </table>