FDA label 3684fb8d-5e9d-6912-e054-00144ff88e88

WARNING: HEPATOTOXICITY Hepatotoxicity has been reported with use of SELZENTRY ® . Severe rash or evidence of a systemic allergic reaction (e.g., fever, eosinophilia, or elevated IgE) prior to the development of hepatotoxicity may occur. Patients with signs or symptoms of hepatitis or allergic reaction following use of SELZENTRY should be evaluated immediately [see Warnings and Precautions (5.1)] . WARNING: HEPATOTOXICITY See full prescribing information for complete boxed warning. Hepatotoxicity has been reported which may be preceded by severe rash or other features of a systemic allergic reaction (e.g., fever, eosinophilia, or elevated IgE). ( 5.1 ) Immediately evaluate patients with signs or symptoms of hepatitis or allergic reaction. ( 5.1 )

5 WARNINGS AND PRECAUTIONS Hepatotoxicity accompanied by severe rash or systemic allergic reaction, including potentially life-threatening events, has been reported. Hepatic laboratory parameters including ALT, AST, and bilirubin should be obtained prior to starting SELZENTRY and at other time points during treatment as clinically indicated. If rash or symptoms or signs of hepatitis or allergic reaction develop, hepatic laboratory parameters should be monitored and discontinuation of treatment should be considered. Use caution when administering SELZENTRY to patients with pre-existing liver dysfunction or who are co-infected with hepatitis B and/or C virus. ( 5.1 ) Severe and potentially life-threatening skin and hypersensitivity reactions have been reported in patients taking SELZENTRY. This includes cases of Stevens-Johnson syndrome, hypersensitivity reaction, and toxic epidermal necrolysis. Immediately discontinue SELZENTRY and other suspected agents if signs or symptoms of severe skin or hypersensitivity reactions develop and monitor clinical status, including liver aminotransferases, closely. ( 5.2 ) More cardiovascular events, including myocardial ischemia and/or infarction, were observed in treatment-experienced subjects who received SELZENTRY. Use with caution in patients at increased risk of cardiovascular events. ( 5.3 ) If patients with severe renal impairment or ESRD receiving SELZENTRY (without concomitant CYP3A inducers or inhibitors) experience postural hypotension, the dose of SELZENTRY should be reduced from 300 mg twice daily to 150 mg twice daily. ( 5.3 ) 5.1 Hepatotoxicity Hepatotoxicity with allergic features including life-threatening events has been reported in clinical trials and postmarketing. Severe rash or evidence of systemic allergic reaction including drug-related rash with fever, eosinophilia, elevated IgE, or other systemic symptoms have been reported in conjunction with hepatotoxicity . These events occurred approximately 1 month after starting treatment. Among reported cases of hepatitis, some were observed in the absence of allergic features or with no pre-existing hepatic disease. Hepatotoxicity with allergic features including life-threatening events has been reported in clinical trials and postmarketing. Severe rash or evidence of systemic allergic reaction including drug-related rash with fever, eosinophilia, elevated IgE, or other systemic symptoms have been reported in conjunction with hepatotoxicity [see Warnings and Precautions (5.2)] . These events occurred approximately 1 month after starting treatment. Among reported cases of hepatitis, some were observed in the absence of allergic features or with no pre-existing hepatic disease. Appropriate laboratory testing including ALT, AST, and bilirubin should be conducted prior to initiating therapy with SELZENTRY and at other time points during treatment as clinically indicated. Hepatic laboratory parameters should be obtained in any patient who develops rash, or signs or symptoms of hepatitis, or allergic reaction. Discontinuation of SELZENTRY should be considered in any patient with signs or symptoms of hepatitis, or with increased liver transaminases combined with rash or other systemic symptoms.Appropriate laboratory testing including ALT, AST, and bilirubin should be conducted prior to initiating therapy with SELZENTRY and at other time points during treatment as clinically indicated. Hepatic laboratory parameters should be obtained in any patient who develops rash, or signs or symptoms of hepatitis, or allergic reaction. Discontinuation of SELZENTRY should be considered in any patient with signs or symptoms of hepatitis, or with increased liver transaminases combined with rash or other systemic symptoms. Caution should be used when administering SELZENTRY to patients with pre-existing liver dysfunction or who are co-infected with hepatitis B and/or C virus. The safety and efficacy of SELZENTRY have not been specifically studied in patients with significant underlying liver disorders. 5.2 Severe Skin and Hypersensitivity Reactions Severe, potentially life-threatening skin and hypersensitivity reactions have been reported in patients taking SELZENTRY, in most cases concomitantly with other drugs associated with these reactions. These include cases of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) [see Adverse Reactions (6.2)] . The cases were characterized by features including rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure. Discontinue SELZENTRY and other suspected agents immediately if signs or symptoms of severe skin or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, malaise, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, lip swelling, eosinophilia). Delay in stopping treatment with SELZENTRY or other suspect drugs after the onset of rash may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated. 5.3 Cardiovascular Events Use with caution in patients at increased risk for cardiovascular events. Eleven subjects (1.3%) who received SELZENTRY had cardiovascular events, including myocardial ischemia and/or infarction, during the Phase 3 trials in treatment-experienced subjects (total exposure 609 patient-years [300 on SELZENTRY once daily + 309 on SELZENTRY twice daily]), while no subjects who received placebo had such events (total exposure 111 patient-years). These subjects generally had cardiac disease or cardiac risk factors prior to use of SELZENTRY, and the relative contribution of SELZENTRY to these events is not known. In the Phase 2b/3 trial in treatment-naive subjects, 3 subjects (0.8%) who received SELZENTRY had events related to ischemic heart disease and 5 subjects (1.4%) who received efavirenz had such events (total exposure 506 and 508 patient-years for SELZENTRY and efavirenz, respectively). When SELZENTRY was administered to healthy volunteers at doses higher than the recommended dose, symptomatic postural hypotension was seen at a greater frequency than in placebo. However, when SELZENTRY was given at the recommended dose in HIV-1-infected subjects in Phase 3 trials, postural hypotension was seen at a rate similar to placebo (approximately 0.5%). Caution should be used when administering SELZENTRY in patients with a history of or risk factors for postural hypotension, cardiovascular comorbidities, or on concomitant medication known to lower blood pressure. Patients with cardiovascular comorbidities could be at increased risk of cardiovascular adverse events triggered by postural hypotension. Postural Hypotension in Patients with Renal Impairment An increased risk of postural hypotension may occur in patients with severe renal insufficiency or in those with ESRD due to increased maraviroc exposure in some patients. SELZENTRY should be used in patients with severe renal impairment or ESRD only if they are not receiving a concomitant potent CYP3A inhibitor or inducer. However, the use of SELZENTRY in these patients should only be considered when no alternative treatment options are available. If patients with severe renal impairment or ESRD experience any symptoms of postural hypotension while taking 300 mg twice daily, the dose should be reduced to 150 mg twice daily [see Dosage and Administration (2.2)] . 5.4 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including SELZENTRY. 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 with Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis, or reactivation of Herpes simplex and Herpes zoster), 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. 5.5 Potential Risk of Infection SELZENTRY antagonizes the CCR5 co-receptor located on some immune cells, and therefore could potentially increase the risk of developing infections. The overall incidence and severity of infection, as well as AIDS-defining category C infections, were comparable in the treatment groups during the Phase 3 treatment-experienced trials of SELZENTRY. While there was a higher rate of certain upper respiratory tract infections reported in the treatment arm receiving SELZENTRY compared with placebo (23% versus 13%), there was a lower rate of pneumonia (2% versus 5%) reported in subjects receiving SELZENTRY. A higher incidence of Herpes virus infections (11 per 100 patient-years) was also reported in the treatment arm receiving SELZENTRY when adjusted for exposure compared with placebo (8 per 100 patient-years). In the Phase 2b/3 trial in treatment-naive subjects, the incidence of AIDS-defining Category C events when adjusted for exposure was 1.8 for SELZENTRY compared with 2.4 for efavirenz per 100 patient-years of exposure. Patients should be monitored closely for evidence of infections while receiving SELZENTRY. 5.6 Potential Risk of Malignancy While no increase in malignancy has been observed with SELZENTRY, due to this drug’s mechanism of action it could affect immune surveillance and lead to an increased risk of malignancy. The exposure-adjusted rate for malignancies per 100 patient-years of exposure in treatment-experienced trials was 4.6 for SELZENTRY compared with 9.3 on placebo. In treatment-naive subjects, the rates were 1.0 and 2.4 per 100 patient-years of exposure for SELZENTRY and efavirenz, respectively. Long-term follow-up is needed to more fully assess this risk.

6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Hepatotoxicity [see Boxed Warning, Warnings and Precautions (5.1)] Severe Skin and Hypersensitivity Reactions [see Warnings and Precautions (5.2)] Cardiovascular events [see Warnings and Precautions (5.3)] The most common adverse events in treatment-experienced subjects (greater than 8% incidence) which occurred at a higher frequency compared with placebo are upper respiratory tract infections, cough, pyrexia, rash, and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ViiV Healthcare at 1-877-844-8872 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 cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Treatment-experienced Subjects The safety profile of SELZENTRY is primarily based on 840 HIV-1-infected subjects who received at least 1 dose of SELZENTRY during two Phase 3 trials. A total of 426 of these subjects received the indicated twice-daily dosing regimen. Assessment of treatment-emergent adverse events is based on the pooled data from 2 trials in subjects with CCR5-tropic HIV-1 (A4001027 and A4001028). The median duration of therapy with SELZENTRY for subjects in these trials was 48 weeks, with the total exposure on SELZENTRY twice daily at 309 patient-years versus 111 patient-years on placebo + optimized background therapy (OBT). The population was 89% male and 84% white, with mean age of 46 years (range: 17 to 75 years). Subjects received dose equivalents of 300 mg maraviroc once or twice daily. The most common adverse events reported with twice-daily therapy with SELZENTRY with frequency rates higher than placebo, regardless of causality, were upper respiratory tract infections, cough, pyrexia, rash, and dizziness. In these 2 trials, the rate of discontinuation due to adverse events was 5% for subjects who received SELZENTRY twice daily + OBT as well as those who received placebo + OBT. Most of the adverse events reported were judged to be mild to moderate in severity. The data described below occurred with twice-daily dosing of SELZENTRY. The total number of subjects reporting infections were 233 (55%) and 84 (40%) in the group receiving SELZENTRY twice daily and the placebo group, respectively. Correcting for the longer duration of exposure on SELZENTRY compared with placebo, the exposure-adjusted frequency (rate per 100 subject-years) of these events was 133 for both SELZENTRY twice daily and placebo. Dizziness or postural dizziness occurred in 8% of subjects on either SELZENTRY or placebo, with 2 subjects (0.5%) on SELZENTRY permanently discontinuing therapy (1 due to syncope, 1 due to orthostatic hypotension) versus 1 subject on placebo (0.5%) permanently discontinuing therapy due to dizziness. Treatment-emergent adverse events, regardless of causality, from Trials A4001027 and A4001028 are summarized in Table 3. Selected events occurring at greater than or equal to 2% of subjects and at a numerically higher rate in subjects treated with SELZENTRY are included; events that occurred at the same or higher rate on placebo are not displayed. Table 3. Percentage of Subjects with Selected Treatment-emergent Adverse Events (All Causality) Greater than or Equal to 2% on SELZENTRY (and at a higher rate compared with placebo) Trials A4001027 and A4001028 (Pooled Analysis, 48 Weeks) SELZENTRY Twice Daily a Placebo Body System/ Adverse Event (n = 426) % Exposure-adjusted Rate (per 100 pt-yrs) PYE = 309 b (n = 209) % Exposure-adjusted Rate (per 100 pt-yrs) PYE = 111 b Eye Disorders Conjunctivitis 2 3 1 3 Ocular infections, inflammations, and associated manifestations 2 3 1 2 Gastrointestinal Disorders Constipation 6 9 3 6 General Disorders and Administration Site Conditions Pyrexia 13 20 9 17 Pain and discomfort 4 5 3 5 Infections and Infestations Upper respiratory tract infection 23 37 13 27 Herpes infection 8 11 4 8 Sinusitis 7 10 3 6 Bronchitis 7 9 5 9 Folliculitis 4 5 2 4 Pneumonia 2 3 5 10 Anogenital warts 2 3 1 3 Influenza 2 3 0.5 1 Otitis media 2 3 0.5 1 Metabolism and Nutrition Disorders Appetite disorders 8 11 7 13 Musculoskeletal and Connective Tissue Disorders Joint-related signs and symptoms 7 10 3 5 Muscle pains 3 4 0.5 1 Neoplasms Benign, Malignant, and Unspecified Skin neoplasms benign 3 4 1 3 Nervous System Disorders Dizziness/postural dizziness 9 13 8 17 Paresthesias and dysesthesias 5 7 3 6 Sensory abnormalities 4 6 1 3 Disturbances in consciousness 4 5 3 6 Peripheral neuropathies 4 5 3 6 Psychiatric Disorders Disturbances in initiating and maintaining sleep 8 11 5 10 Depressive disorders 4 6 3 5 Anxiety symptoms 4 5 3 7 Renal and Urinary Disorders Bladder and urethral symptoms 5 7 1 3 Urinary tract signs and symptoms 3 4 1 3 Respiratory, Thoracic, and Mediastinal Disorders Coughing and associated symptoms 14 21 5 10 Upper respiratory tract signs and symptoms 6 9 3 6 Nasal congestion and inflammations 4 6 3 5 Breathing abnormalities 4 5 2 5 Paranasal sinus disorders 3 4 0.5 1 Skin and Subcutaneous Tissue Disorders Rash 11 16 5 11 Apocrine and eccrine gland disorders 5 7 4 7.5 Pruritus 4 5 2 4 Lipodystrophies 3 5 0.5 1 Erythemas 2 3 1 2 Vascular Disorders Vascular hypertensive disorders 3 4 2 4 a 300-mg dose equivalent. b PYE = Patient-years of exposure. Laboratory Abnormalities Table 4 shows the treatment-emergent Grade 3-4 laboratory abnormalities that occurred in greater than 2% of subjects receiving SELZENTRY. Table 4. Maximum Shift in Laboratory Test Values (without Regard to Baseline) Incidence Greater than or Equal to 2% of Grade 3-4 Abnormalities (ACTG Criteria) Trials A4001027 and A4001028 (Pooled Analysis, 48 Weeks) Laboratory Parameter Preferred Term Limit SELZENTRY Twice Daily + OBT (n = 421) a % Placebo + OBT (n = 207) a % Aspartate aminotransferase >5.0 x ULN 4.8 2.9 Alanine aminotransferase >5.0 x ULN 2.6 3.4 Total bilirubin >2.5 x ULN 5.5 5.3 Amylase >2.0 x ULN 5.7 5.8 Lipase >2.0 x ULN 4.9 6.3 Absolute neutrophil count <750/mm 3 4.3 2.4 a Percentages based on total subjects evaluated for each laboratory parameter. ULN=upper limit of normal. Treatment ‑ naive Subjects Treatment ‑e mergent Adverse Events : Treatment‑emergent adverse events, regardless of causality, from Trial A4001026, a double‑blind, comparative, controlled trial in which 721 treatment‑naive subjects received SELZENTRY 300 mg twice daily (n = 360) or efavirenz 600 mg once daily (n = 361) in combination with lamivudine/zidovudine (COMBIVIR ® ) for 96 weeks, are summarized in Table 5. Selected events occurring in greater than or equal to 2% of subjects and at a numerically higher rate in subjects treated with SELZENTRY are included; events that occurred at the same or higher rate on efavirenz are not displayed. Table 5. Percentage of Subjects with Selected Treatment-emergent Adverse Events (All Causality) Greater than or Equal to 2% on SELZENTRY (and at a higher rate compared with efavirenz) Trial A4001026 (96 Weeks) Body System/ Adverse Event SELZENTRY 300 mg Twice Daily + Lamivudine/Zidovudine (n = 360) % Efavirenz 600 mg Once Daily + Lamivudine/Zidovudine (n = 361) % Blood and Lymphatic System Disorders Anemias NEC 8 5 Neutropenias 4 3 Ear and Labyrinth Disorders Ear disorders NEC 3 2 Gastrointestinal Disorders Flatulence, bloating, and distention 10 7 Gastrointestinal atonic and hypomotility disorders NEC 9 5 Gastrointestinal signs and symptoms NEC 3 2 General Disorders and Administration Site Conditions Body temperature perception 3 1 Infections and Infestations Bronchitis 13 9 Herpes infection 7 6 Upper respiratory tract infection 32 30 Bacterial infections NEC 6 3 Herpes zoster/varicella 5 4 Lower respiratory tract and lung infections 3 2 Neisseria infections 3 0 Tinea infections 4 3 Viral infections NEC 3 2 Musculoskeletal and Connective Tissue Disorders Joint-related signs and symptoms 6 5 Nervous System Disorders Memory loss (excluding dementia) 3 1 Paresthesias and dysesthesias 4 3 Renal and Urinary Disorders Bladder and urethral symptoms 4 3 Reproductive System and Breast Disorders Erection and ejaculation conditions and disorders 3 2 Respiratory, Thoracic, and Mediastinal Disorders Upper respiratory tract signs and symptoms 9 5 Skin and Subcutaneous Disorders Acnes 3 2 Alopecias 2 1 Lipodystrophies 4 3 Nail and nail bed conditions (excluding infections and infestations) 6 2 Laboratory Abnormalities Table 6. Maximum Shift in Laboratory Test Values (without Regard to Baseline) Incidence Greater than or Equal to 2% of Grade 3-4 Abnormalities (ACTG Criteria) Trial A4001026 (96 Weeks) Laboratory Parameter Preferred Term Limit SELZENTRY 300 mg Twice Daily + Lamivudine/Zidovudine (n = 353) a % Efavirenz 600 mg Once Daily+ Lamivudine/Zidovudine (n = 350) a % Aspartate aminotransferase >5.0 x ULN 4.0 4.0 Alanine aminotransferase >5.0 x ULN 3.9 4.0 Creatine kinase – 3.9 4.8 Amylase >2.0 x ULN 4.3 6.0 Absolute neutrophil count <750/mm 3 5.7 4.9 Hemoglobin <7.0 g/dL 2.9 2.3 a n = Total number of subjects evaluable for laboratory abnormalities. ULN=upper limit of normal. Percentages based on total subjects evaluated for each laboratory parameter. If the same subject in a given treatment group had greater than 1 occurrence of the same abnormality, only the most severe is counted. Less Common Adverse Events in Clinical Trials The following adverse events occurred in less than 2% of subjects treated with SELZENTRY or at a rate similar to the comparator. These events have been included because of their seriousness and either increased frequency on SELZENTRY or are potential risks due to the mechanism of action. Events attributed to the subjects’ underlying HIV-1 infection are not listed. Blood and Lymphatic System: Marrow depression and hypoplastic anemia. Cardiac Disorders: Unstable angina, acute cardiac failure, coronary artery disease, coronary artery occlusion, myocardial infarction, myocardial ischemia. Hepatobiliary Disorders: Hepatic cirrhosis, hepatic failure, cholestatic jaundice, portal vein thrombosis, jaundice. Infections and Infestations: Endocarditis, infective myositis, viral meningitis, pneumonia, treponema infections, septic shock, Clostridium difficile colitis, meningitis. Musculoskeletal and Connective Tissue Disorders: Myositis, osteonecrosis, rhabdomyolysis, blood CK increased. Neoplasms Benign, Malignant, and Unspecified (Including Cysts and Polyps): Abdominal neoplasm, anal cancer, basal cell carcinoma, Bowen’s disease, cholangiocarcinoma, diffuse large B-cell lymphoma, lymphoma, metastases to liver, esophageal carcinoma, nasopharyngeal carcinoma, squamous cell carcinoma, squamous cell carcinoma of skin, tongue neoplasm (malignant stage unspecified), anaplastic large cell lymphomas T- and null-cell types, bile duct neoplasms malignant, endocrine neoplasms malignant and unspecified. Nervous System Disorders: Cerebrovascular accident, convulsions and epilepsy, tremor (excluding congenital), facial palsy, hemianopia, loss of consciousness, visual field defect. 6.2 Postmarketing Experience The following events have been identified during post-approval use of SELZENTRY and are not listed above. Because these reactions are reported voluntarily from a population of unknown size, it is not possible to estimate their frequency or establish a causal relationship to exposure to SELZENTRY. Skin and Subcutaneous Tissue Disorders Stevens‑Johnson syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), toxic epidermal necrolysis (TEN).

<table ID="_RefID0EBUAE" width="100%"> <caption>Trials A4001027 and A4001028 (Pooled Analysis, 48 Weeks)</caption> <col width="42%"/> <col width="10%"/> <col width="19%"/> <col width="10%"/> <col width="19%"/> <tbody> <tr> <td styleCode="Rrule Lrule Toprule " valign="bottom"/> <td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="bottom"> <paragraph> <content styleCode="bold">SELZENTRY</content> </paragraph> <paragraph> <content styleCode="bold">Twice Daily ^a </content> </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="bottom"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> </td> </tr> <tr> <td align="center" styleCode="Rrule Lrule Botrule " valign="bottom"> <paragraph> <content styleCode="bold">Body System/</content> </paragraph> <paragraph> <content styleCode="bold">Adverse Event</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="bottom"> <paragraph> <content styleCode="bold">(n = 426)</content> </paragraph> <paragraph> <content styleCode="bold">%</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="bottom"> <paragraph> <content styleCode="bold">Exposure-adjusted Rate</content> </paragraph> <paragraph> <content styleCode="bold">(per 100 pt-yrs)</content> </paragraph> <paragraph> <content styleCode="bold">PYE = 309 ^b </content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="bottom"> <paragraph> <content styleCode="bold">(n = 209)</content> </paragraph> <paragraph> <content styleCode="bold">%</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="bottom"> <paragraph> <content styleCode="bold">Exposure-adjusted Rate</content> </paragraph> <paragraph> <content styleCode="bold">(per 100 pt-yrs)</content> </paragraph> <paragraph> <content styleCode="bold">PYE = 111 ^b </content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Eye Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Conjunctivitis </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>1</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Ocular infections, inflammations, and associated manifestations</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Gastrointestinal Disorders </content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Constipation</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>6</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">General Disorders and Administration Site Conditions</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Pyrexia </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>13</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>20</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>9</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>17</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Pain and discomfort </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Infections and Infestations </content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Upper respiratory tract infection</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>23</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>37</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>13</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>27</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Herpes infection</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>8</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>11</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>8</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Sinusitis</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>7</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>10</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>6</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Bronchitis</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>7</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>9</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>9</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Folliculitis</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Pneumonia </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>10</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Anogenital warts </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>1</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Influenza </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>0.5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Otitis media</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>0.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Metabolism and Nutrition Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Appetite disorders</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>8</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>11</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>7</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>13</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Musculoskeletal and Connective Tissue Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Joint-related signs and symptoms</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>7</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>10</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Muscle pains</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>0.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Neoplasms Benign, Malignant, and Unspecified</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Skin neoplasms benign</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Nervous System Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Dizziness/postural dizziness </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>9</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>13</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>8</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>17</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Paresthesias and dysesthesias</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>7</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>6</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Sensory abnormalities</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>6</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>1</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Disturbances in consciousness</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>6</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Peripheral neuropathies</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>6</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Psychiatric Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Disturbances in initiating and maintaining sleep</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>8</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>11</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>10</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Depressive disorders</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>6</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Anxiety symptoms</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>7</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Renal and Urinary Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Bladder and urethral symptoms</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>7</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>1</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Urinary tract signs and symptoms</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Respiratory, Thoracic, and Mediastinal Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Coughing and associated symptoms </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>14</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>21</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>10</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Upper respiratory tract signs and symptoms</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>6</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>9</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>6</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Nasal congestion and inflammations </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>6</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Breathing abnormalities</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Paranasal sinus disorders </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>0.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Rash </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>11</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>16</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>11</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Apocrine and eccrine gland disorders</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>7</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>7.5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Pruritus </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Lipodystrophies </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>0.5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Erythemas</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>1</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Vascular Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Botrule Lrule " valign="top"> <paragraph>Vascular hypertensive disorders</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4</paragraph> </td> </tr> </tbody> </table>

<table ID="_RefID0EQNAG" width="100%"> <caption>Incidence Greater than or Equal to 2% of Grade 3-4 Abnormalities (ACTG Criteria) Trials A4001027 and A4001028 (Pooled Analysis, 48 Weeks)</caption> <col width="44%"/> <col width="14%"/> <col width="23%"/> <col width="19%"/> <tbody> <tr> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="bottom"> <paragraph> <content styleCode="bold">Laboratory Parameter Preferred Term</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Toprule " valign="bottom"> <paragraph> <content styleCode="bold">Limit</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Toprule " valign="bottom"> <paragraph> <content styleCode="bold">SELZENTRY</content> </paragraph> <paragraph> <content styleCode="bold">Twice Daily + OBT</content> </paragraph> <paragraph> <content styleCode="bold">(n = 421) ^a </content> </paragraph> <paragraph> <content styleCode="bold">%</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Toprule " valign="bottom"> <paragraph> <content styleCode="bold">Placebo + OBT</content> </paragraph> <paragraph> <content styleCode="bold">(n = 207) ^a </content> </paragraph> <paragraph> <content styleCode="bold">%</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Aspartate aminotransferase</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&gt;5.0 x ULN</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4.8</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2.9</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Alanine aminotransferase</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&gt;5.0 x ULN</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2.6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3.4</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Total bilirubin</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&gt;2.5 x ULN</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5.5</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5.3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Amylase</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&gt;2.0 x ULN</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5.7</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5.8</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Lipase</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&gt;2.0 x ULN</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4.9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>6.3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule " valign="top"> <paragraph>Absolute neutrophil count</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>&lt;750/mm ³ </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4.3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2.4</paragraph> </td> </tr> </tbody> </table>

<table ID="_RefID0ERSAG" width="100%"> <caption>Table 5. Percentage of Subjects with Selected Treatment-emergent Adverse Events (All Causality) Greater than or Equal to 2% on SELZENTRY (and at a higher rate compared with efavirenz) Trial A4001026 (96 Weeks)</caption> <col width="43%"/> <col width="30%"/> <col width="27%"/> <tbody> <tr> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="bottom"> <paragraph> <content styleCode="bold">Body System/</content> </paragraph> <paragraph> <content styleCode="bold">Adverse Event</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Toprule " valign="bottom"> <paragraph> <content styleCode="bold">SELZENTRY 300 mg Twice Daily +</content> </paragraph> <paragraph> <content styleCode="bold">Lamivudine/Zidovudine</content> </paragraph> <paragraph> <content styleCode="bold">(n = 360)</content> </paragraph> <paragraph> <content styleCode="bold">%</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Toprule " valign="bottom"> <paragraph> <content styleCode="bold">Efavirenz 600 mg Once Daily +</content> </paragraph> <paragraph> <content styleCode="bold">Lamivudine/Zidovudine</content> </paragraph> <paragraph> <content styleCode="bold">(n = 361)</content> </paragraph> <paragraph> <content styleCode="bold">%</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Blood and Lymphatic System Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Anemias NEC</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>8</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Neutropenias</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Ear and Labyrinth Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Ear disorders NEC</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Gastrointestinal Disorders </content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Flatulence, bloating, and distention</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>10</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>7</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Gastrointestinal atonic and hypomotility disorders NEC</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>9</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Gastrointestinal signs and symptoms NEC</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">General Disorders and Administration Site Conditions</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Body temperature perception </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Infections and Infestations </content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Bronchitis</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>13</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>9</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Herpes infection</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>7</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>6</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Upper respiratory tract infection</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>32</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>30</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Bacterial infections NEC</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>6</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Herpes zoster/varicella</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Lower respiratory tract and lung infections</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="italics">Neisseria</content> infections </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>0</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Tinea infections</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Viral infections NEC</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Musculoskeletal and Connective Tissue Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Joint-related signs and symptoms</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Nervous System Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Memory loss (excluding dementia)</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Paresthesias and dysesthesias </paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Renal and Urinary Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Bladder and urethral symptoms</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Reproductive System and Breast Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Erection and ejaculation conditions and disorders</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Respiratory, Thoracic, and Mediastinal Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Upper respiratory tract signs and symptoms</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>9</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Skin and Subcutaneous Disorders</content> </paragraph> </td> <td styleCode="Rrule " valign="top"/> <td styleCode="Rrule " valign="top"/> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Acnes</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Alopecias</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>2</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Lipodystrophies</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>4</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <paragraph>3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule " valign="top"> <paragraph>Nail and nail bed conditions (excluding infections and infestations)</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>6</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <paragraph>2</paragraph> </td> </tr> </tbody> </table>