Drug Interaction Study

Cmax of ATV

Cmax was derived from the plasma concentration versus time for ATV and was recorded directly from experimental observations for each treatment period.

Time frame: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.

Cmin of ATV

Cmin was derived from the plasma concentration versus time for ATV.

Time frame: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.

AUC(TAU) for ATV

AUC(TAU) was derived from the plasma concentration versus time for ATV, and was calculated by linear and log-linear trapezoidal summations using a mixed log-linear algorithm.

Time frame: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.

Time to Reach Maximum Observed Plasma Concentration (Tmax) of ATV

Tmax was derived from the plasma concentration versus time for ATV and was recorded directly from experimental observations for each treatment period.

Time frame: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.

Terminal Elimination Half-life (T-half) of ATV

T-half was obtained directly from the concentration-time data. T-half following doses administered for treatment ATV/RTV 300/100 mg QD+RIB 150 mg twice weekly.

Time frame: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.

Cmax of RTV

Cmax was derived from the plasma concentration versus time for RTV and was recorded directly from experimental observations for each treatment period.

Time frame: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.

Cmin of RTV

Cmin was derived from the plasma concentration versus time for RTV.

Time frame: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.

AUC(TAU) for RTV

AUC(TAU) was derived from the plasma concentration versus time for RTV, and was calculated by linear and log-linear trapezoidal summations using a mixed log-linear algorithm.

Time frame: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.

Tmax of RTV

Tmax was derived from the plasma concentration versus time for RTV and was recorded directly from experimental observations for each treatment period.

Time frame: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.

T-half of RTV

T-half was obtained directly from the concentration-time data.

Time frame: Pre-dose (0h) on Days 4, 8, 11 to 18 and post-dose (1h,2h,3h,4h,6h,8h,12h) on Days 11 and 15 for ATV/RTV + RIB.

Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced Events Leading to Discontinuation.

AEs were defined as new, untoward medical occurrences/worsening of pre-existing medical condition, whether drug-related or not. SAEs were defined as any AE that: resulted in death; was life threatening; resulted in a persistent or significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; was a cancer; or was an overdose. Discontinuation from the study was due either to an AE or was conducted at the investigator's discretion.

Time frame: From Day 1 to 30 days after the last dose of study drug.

Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Platelet Count and Leukocytes

MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Hemoglobin/hematocrit: \<0.85 x pre-treatment (pre-Rx) value. Platelet count: \<0.85 x lower limit of normal (LLN) (or, if pre-Rx value \<LLN, then \<0.85 x pre-Rx value) or \>1.5 x upper limit of normal (ULN). Leukocytes: \<0.9 x LLN or \>1.2 x ULN (or, if pre-Rx value \<LLN, then \<0.85 x pre-Rx or \>ULN. If pre-Rx value \>ULN, then \>1.15 x pre-Rx or \<LLN).

Time frame: Pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14, 20 and 26 for RIB 150 mg QD; and pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14 and 18 for ATV/RTV 300/100 mg QD + RIB 150 mg twice weekly.

Number of Participants With MAs in Hematology: Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)

MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Neutrophils+bands (absolute): \<=1.50 x 10\^3 cells/microliter (uL). Lymphocytes (absolute): \<0.75 x 10\^3 cells/uL or \>7.50 x 10\^3 cells/uL. Monocytes (absolute): \>2.00 x 10\^3 cells/uL. Basophils (absolute): \>0.40 x 10\^3 cells/uL. Eosinophils (absolute): \>0.75 x 10\^3 cells/uL.

Time frame: Pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14, 20 and 26 for RIB 150 mg QD; and pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14 and 18 for ATV/RTV 300/100 mg QD + RIB 150 mg twice weekly.

Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP),Aspartate Aminotransferase (AST),Alanine Aminotransferase (ALT),Bilirubin (Total),Bilirubin (Direct),Blood Urea Nitrogen (BUN),Creatinine,Sodium (Serum),Potassium (Serum)

MAs=laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria. ALP, AST, ALT:\>1.25xULN (if pre-Rx \>ULN, then \>1.25xpre-Rx). Bilirubin (total), bilirubin (direct), BUN:\>1.1xULN (if pre-Rx \>ULN, then \>1.25xpre-Rx). Creatinine:\>1.33xpre-Rx. Sodium (serum):\<0.95xLLN or \>1.05xULN (if pre-Rx \<LLN, then \<0.95xpre-Rx or \>ULN. If pre-Rx \>ULN, then \>1.05xpre-Rx or \<LLN). Potassium (serum):\<0.9xLLN or \>1.1xULN (if pre-Rx \<LLN, then \<0.9xpre-Rx or \>ULN. If pre-Rx \>ULN, then \>1.1xpre-Rx or \<LLN).

Time frame: Pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14, 20 and 26 for RIB 150 mg QD; and pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14 and 18 for ATV/RTV 300/100 mg QD + RIB 150 mg twice weekly.

Number of Participants With MAs in Serum Chemistry: Chloride (Serum), Calcium (Total), Protein (Total), Bicarbonate, Phosphorous (Inorganic)

MAs=laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria. Chloride (serum), calcium (total), protein (total):\<0.9xLLN or \>1.1xULN (if pre-Rx \<LLN, then \<0.9xpre-Rx or \>ULN. If pre-Rx \>ULN, then \>1.1xpre-Rx or \<LLN). Bicarbonate:\<0.8xLLN or \>1.2xULN (if pre-Rx value \<LLN, then \<0.8xpre-Rx value or \>ULN. If pre-Rx \>ULN, then \>1.2xpre-Rx value or \<ULN). Phosphorous (inorganic):\<0.85xLLN or \>1.25xULN (if pre-Rx \<ULN, then \<0.85xpre-Rx or \<ULN. If pre-Rx \>ULN, then \>1.25x re-Rx or \<LLN).

Time frame: Pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14, 20 and 26 for RIB 150 mg QD; and pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14 and 18 for ATV/RTV 300/100 mg QD + RIB 150 mg twice weekly.

Number of Participants With MAs in Serum Chemistry: Glucose (Fasting Serum), Albumin, Creatine Kinase, Uric Acid, Lactate Dehydrogenase (LDH)

MAs=laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria. Glucose (fasting serum): \<0.8 x LLN or \>1.5 ULN (if pre-Rx \<LLN, then \<0.8 x pre-Rx or \>ULN. If pre-Rx \>ULN, then \>2.0 x pre-Rx or \<LLN. Albumin: \<0.9 x LLN (if pre-Rx \<LLN, then \<0.9 x pre-Rx). Creatine kinase: \>1.5 x ULN (if pre-Rx \>ULN, then \>1.5 x pre-Rx). Uric acid: \>1.2 x ULN (if pre-Rx \>ULN, then \>1.25 x pre-Rx). LDH: \>1.25 x ULN (if pre-Rx \>ULN, then \>1.5 x pre-Rx).

Time frame: Pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14, 20 and 26 for RIB 150 mg QD; and pre-dose on Day -1 and post-dose on Days 3, 7, 11, 14 and 18 for ATV/RTV 300/100 mg QD + RIB 150 mg twice weekly.

Number of Participants With MAs in Urinalysis

MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following definitions specify the criteria for MAs. Protein, glucose and blood: \>=2+ (or, if pre-treatment value \>=1+, then \>= 2 x pre-treatment value).

Time frame: Pre-dose on Day -1, Day 7 and discharge.

Number of Participants With Identified Electrocardiogram (ECG) Abnormalities

ECG abnormalities were defined as findings that are clinically meaningful as judged by the investigator. A 12-lead ECG was recorded at least 5 minutes after the participant had been lying down and all ECG recordings were evaluated by the investigator. Abnormalities, if present at any study time point, were listed.

Time frame: Pre-dose on Day -1 and study discharge.

Number of Participants With Clinically Significant Vital Signs or Physical Examination Findings

Vital signs assessments and physical examination were conducted throughout the study. Vital signs assessments included body temperature, respiratory rate, blood pressure (systolic and diastolic), and heart rate. Physical examination included a neurological examination (if ocular signs or symptoms occurred, a reflex to slit lamp exam was performed by an ophthalmologist). The investigator used his/her clinical judgment to decide whether or not abnormalities in vital signs or physical examination were clinically meaningful.

Time frame: Vital signs:screening, prior to dosing on Day 1, Day 7, study discharge. Physical examination:screening, Day -1, Day 7, study discharge