A 96 Week Study Comparing the Antiviral Efficacy and Safety of Atazanavir/Ritonavir With Lopinavir/Ritonavir, Each in Combination With Fixed Dose Tenofovir-Emtricitabine in HIV-1 Infected Treatment in Naive Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,057
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-time Curve, in One Dosing Interval [AUC(TAU)] of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and antiviral effects of atazanavir (ATV) plus ritonavir (RTV) versus a combination drug of lopinavir (LPV) plus RTV. A combination drug containing tenofovir (TDF) and emtricitabine (FTC) will also be taken by participants in both arms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV RNA ≥5000 c/ml
排除标准
- •Any antiretroviral therapy within 30 days prior to screening;
- •Women of Childbearing potential (WOCBP) unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 8 weeks after the study;
- •WOCBP using a prohibited contraceptive method
- •WOCBP who are pregnant or breastfeeding;
- •Women with a positive pregnancy test on enrollment or prior to study drug administration;
- •Presence of a newly diagnosed HIV-Related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment;
- •Suspected primary (acute) HIV infection;
- •Prior antiviral therapy (>30 days of NRTI and/or >7 days of non-nucleoside reverse transcriptase inhibitor (NNRTI) or PI therapies) or any antiretroviral therapy within 30 days prior to screening; some exceptions are allowed for ARV therapy in use for Mother-to-child transmission;
- •Participants with Cushing's syndrome;
- •Untreated hypothyroidism or hyperthyroidism. A participant who is euthyroid on a stable replacement dose of thyroid hormone is acceptable provided the thyroid stimulating hormone (TSH) performed within 30 days of screening is within normal drug range;
- •Recent therapy with agents with significant systemic myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic or cytotoxic potential within 3 months of study start or expected need for such therapy at the time of enrollment; or therapy with methadone or ribavirin/interferons or treatment with neurotoxic drugs or drugs that affect CYP3A4;
- •Participants with obstructive liver disease;
- •Active alcohol or substance use sufficient, in the Investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis;
- •Proven or suspected acute hepatitis in the 30 days prior to study entry;
- •Intractable diarrhea (≥6 loose stools/day for at least 7 consecutive days) within 30 days prior to study entry;
- •Inability to swallow capsules;
- •Active peripheral neuropathy;
- •Presence of cardiomyopathy (due to any cause) or any significant cardiovascular disease, such as unstable ischemic heart disease;
- •Known, clinically significant cardiac conduction system disease.
- •Baseline laboratory values measured within 2 weeks prior to initiating study drugs as follows:
- •calculated creatine clearance <60 mL/min as estimated by the Cockcroft-Gault equation;
- •total serum lipase ≥ 1.4 times the upper limit of normal;
- •liver enzymes (AST, ALT) ≥ 5 times the upper limit of normal;
- •total serum bilirubin ≥ 1.5 times the upper limit of normal.
- •Hypersensitivity to any component of the formulation of study drug;
- •Prohibited therapies;
- •Any other clinical conditions or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for study or unable to comply with the dosing requirements;
- •Prisoners or participants who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
研究组 & 干预措施
Atazanavir (ATV) + Ritonovir (RTV)
Participants were administered an oral dose of ATV 300 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of ATV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks.
干预措施: ATV (Drug)
Atazanavir (ATV) + Ritonovir (RTV)
Participants were administered an oral dose of ATV 300 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of ATV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks.
干预措施: RTV (Drug)
Atazanavir (ATV) + Ritonovir (RTV)
Participants were administered an oral dose of ATV 300 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of ATV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks.
干预措施: Tenofovi-Emtricitabine (TDF/FTC) tablet (Drug)
Lopinavir (LPV) + RTV
Participants were administered an oral dose of LPV 400 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of LPV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks.
干预措施: RTV (Drug)
Lopinavir (LPV) + RTV
Participants were administered an oral dose of LPV 400 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of LPV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks.
干预措施: Tenofovi-Emtricitabine (TDF/FTC) tablet (Drug)
Lopinavir (LPV) + RTV
Participants were administered an oral dose of LPV 400 mg and RTV 100 mg once daily along with food on a background of fixed dose combination TDF 300 mg plus FTC 200 mg (TDF/FTC) once daily. Doses of LPV and RTV were taken 24 hours apart at the same time as the background TDF/FTC, up to 96 Weeks.
干预措施: LPV (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve, in One Dosing Interval [AUC(TAU)] of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.
AUC(TAU) was derived from the plasma concentration versus time data. It was calculated from time 0 to 12 hours for LPV and RTV in the LPV/RTV regimen, 0-24 hours for ATV and RTV in the ATV/RTV regimen, and 0-24 hours for tenofovir in both regimens at Week 4.
AUC (0-24) of RTV at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.
AUC (0-24) was derived from plasma concentration versus time data. It was estimated as 2 times the AUC(TAU) based on 12-hour PK.
Cmin of Tenofovir at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.
Cmin was derived from plasma concentration versus time data.
Mean Change From Baseline in Subcutaneous Adipose Tissue (SAT)-To-Trunk Adipose Tissue (TAT) Ratio Associated With CCDC122_5980
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair. SAT and TAT were measured by computed tomography (CT).
Maximum Plasma Concentration (Cmax) of ATV/RTV and LPV/RTV in the Presence of an Antiretroviral (ARV) Regimen Including TDF at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given every day (QD) and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given twice daily (BID) and TDF given QD.
Cmax was derived from plasma concentration versus time data.
Terminal Elimination Half-life (T-half) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.
T-half was derived from the plasma concentration versus time data.
Inhibitory Quotient (IQ) of ATV and LPV When Dosed With RTV at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.
IQ defined as Cmin at week 4 divided by protein binding adjusted EC90 values for the respective protease inhibitor (ATV or LPV) derived from individual participant clinical isolates.
Cmin of RTV at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.
Cmin was derived from plasma concentration versus time data.
Mean Change From Baseline in Trunk-to-Limb Fat Ratio as Measured by Dual Energy X-ray Absorptiometry (DEXA) at Week 96
时间窗: Baseline (Day 1) and Week 96.
Mean changes from baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values.
Mean Change From Baseline in Fasting Triglycerides Associated With RETN_598
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Protein Binding Adjusted Effective Concentration (EC-90) of ATV and LPV When Dosed With RTV at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.
EC90/50=concentration of drug inducing 90%/50% of its maximal response. Protein binding adjusted EC90 for ATV and LPV were derived from phenotypically measured individual EC50 values at baseline using the following formula: Protein binding adjusted EC90 (ng/mL) = scale factor × molecular weight of the free base × EC50 micrometer(μM)/ unbound fraction (fu). Scale factor relates EC50 to EC90 (value of 3 and 2 for ATV and LPV, respectively); fu: estimated unbound fraction of ATV and LPV in vivo (0.14 and 0.02 for ATV and LPV respectively).
Mean Change From Baseline in Fasting Triglycerides Associated With RETN_097
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Fasting Tumor Necrosis Factor (TNF)-Alpha Asssociated With RS11030679
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Visceral Adipose Tissue (VAT) Associated With BRUNOL_1842
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair. VAT was measured by computed tomography (CT).
Mean Change From Baseline in VAT Associated With RETN_730
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair. VAT was measured by computed tomography (CT).
Mean Change From Baseline in VAT-to-TAT Ratio Associated With CCDA122_5980
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair. VAT and TAT were measured by computed tomography (CT).
Number of Participants With Human-immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) < 50 Copies (c)/mL at Week 48
时间窗: Baseline (Day 1) and Week 48
HIV RNA \< 50 c/mL is the most stringent measure of viral suppression (lowest threshold of assay) and indicates that a participant responded to treatment.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.
Tmax was derived from the plasma concentration versus time data.
Cmax of Tenofovir at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.
Cmax was derived from plasma concentration versus time data.
AUC (TAU) of Tenofovir at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.
AUC (TAU) was derived from plasma concentration versus time data.It was calculated from time 0-24 hours for tenofovir in LPV/RPV and ATV/RTV regimen at Week 4.
Mean Change From Baseline in Fasting Non-High Density Lipoprotein (HDL) Cholesterol Associated With RETN_097
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted (adj) p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Fasting Triglycerides Associated With RETN_2265
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Fasting Triglycerides Associated With APOE_C130R
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Fasting Triglycerides Associated With RETN_734
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Fasting Plasminogen Activator Inhibitor (PAI)-1 Associated With APOE_R176C
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Mean Change From Baseline in Fasting Tumor Necrosis Factor (TNF)-Alpha Associated With IL6_5309
时间窗: Baseline (Day 1), Week 48, and Week 96.
The change-from-baseline was defined as the difference between the averages of post-treatment time points (Weeks 48 and 96) and baseline. Association analysis for each SNP was performed using a minor allele carrier (MAC) composed of heterozygous and rare homozygous genotypes, and wild type (WT, common homozygous). False discovery rate (FDR)-adjusted p-values were calculated for each phenotype-genotype pair.
Minimum Plasma Concentration (Cmin) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.
Cmin was derived from the plasma concentration versus time data.
Cmax of RTV at Week 4
时间窗: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.
Cmax was derived from plasma concentration versus time data.
Number of Participants With Single Nucleotide Polymorphisms (SNPs) Included in Genotype-Phenotype Analysis
时间窗: Baseline visit
19 genes of interest were selected from previous results or literature, and 34 SNPs were genotyped. Phenotype-Genotype analysis was performed using 31 of the SNPs. The genotypes of each SNP were further classified as either a minor allele carrier (MAC) group composed of heterozygous and rare homozygous genotypes, or wild type \[WT, common homozygous\].
次要结局
- Mean Change in Fasting Lipid at Week 48(Baseline (Day 1) and Week 48.)
- Number of Participants With HIV RNA < 400 c/mL at Week 48(Baseline (Day 1) and Week 48)
- Number of Participants With Laboratory Abnormalities in Serum Enzymes Levels Through Week 48(At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.)
- Number of Participants With Laboratory Abnormalities in Liver Function Test Through Week 48(At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.)
- Number of Participants With Laboratory Abnormalities in Renal Function Test Through Week 48(At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, and 48.)
- Number of Participants With Confirmed Plasma HIV RNA < 400 c/mL at Week 48 (Defined by the Food and Drug Administration [FDA] Time to Loss of Virologic Response [TLOVR] Algorithm)(Baseline (Day 1) and Week 48)
- Reduction of log10 HIV RNA Levels From Baseline to Week 48(Baseline (Day 1) and Week 48)
- Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48(Baseline (Day 1) and Week 48.)
- Treatment Emergent Resistance in Isolates From Participants With Virologic Failure at Week 48(Baseline (Day 1) and Week 48)
- Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced AEs Leading to Discontinuation Through Week 48(From baseline (Day 1) to Week 48.)
- Mean Change in Weight From Baseline at Week 48(Baseline (Day 1) and Week 48)
- Mean Change in Fasting Glucose at Week 48(Baseline (Day 1) and Week 48.)
- Mean Change From Baseline in Quality of Life as Measured by the Medical Outcomes Survey - Human Immunodeficiency Virus (MOS-HIV) at Week 48(Baseline (Day 1) and Week 48)
- Mean Change From Baseline in Quality of Life as Measured by the Impact of Gastro-intestinal Toxicity at Week 12 (IBS-QoL)(IBS-QoL is administered at baseline (Day 1) and Week 12.)
- Number of Participants Who Adhered to Regimen as Measured by Multicenter AIDS Cohort Study Adherence Questionnaire (MACS) at Week 48(Week 48)
- Number of Participants With Laboratory Abnormalities in Hematology Through Week 48: Hemoglobin, Hematocrit, Platelet Count, International Normalized Ratio (INR), Neutrophils, Prothrombin Time (PT) and White Blood Cells (WBC)(At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.)
- Mean Change From Baseline in Quality of Life as Measured by the Medical Outcomes Survey - Human Immunodeficiency Virus (MOS-HIV) at Week 24(Baseline (Day 1) and Week 24.)
- Number of Participants With Laboratory Abnormalities in Liver Function Test Through Week 96(At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.)
- Number of Participants With Laboratory Abnormalities in Fasting Lipids Level Through Week 96(At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.)
- Number of Participants With Laboratory Abnormalities in Fasting Glucose Levels Through Week 96(At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.)
- Mean Percent Changes From Baseline in Limb, Trunk and Total Body Fat Measured by DEXA at Week 48(DEXA scans were performed at baseline (within 30 days of starting study treatment), and at Weeks 48.)
- Number of Participants With Laboratory Abnormalities in Electrolytes Through Week 48(At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.)
- Number of Participants With Laboratory Abnormalities in Fasting Lipids Through Week 48(At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.)
- Number of Participants With HIV RNA < 400 c/mL) at Week 96(Baseline (Day 1) and Week 96)
- Mean Changes in Fasting Lipids at Week 96(At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.)
- Number of Participants With Laboratory Abnormalities in Electrolytes Level Through Week 96(At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.)
- Mean Change From Baseline in Body Weight at Week 96(Baseline (Day 1) and Week 96)
- Percentage of Participants With Lipoatrophy at Week 96(Baseline (Day 1) and Week 96)
- Number of Participants With Laboratory Abnormalities in Urinalysis Through Week 48(At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.)
- Number of Participants With Laboratory Abnormalities in Fasting Glucose Through Week 48(At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.)
- Mean Change in Body Mass Index (BMI) in Participants at Week 48(Baseline (Day 1) and Week 48)
- Mean Change From Baseline (BL) in Quality of Life as Measured by the Impact of Gastro-intestinal Toxicity at Week 4 (IBS-QoL)(IBS-QoL is administered at baseline (Day 1) and Week 4.)
- Number of Participants With HIV RNA < 50 c/mL) at Week 96(Baseline (Day 1) and Week 96)
- Mean Change From Baseline in CD4 Cell Count at Week 96(Baseline (Day 1) and Week 96)
- Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced Events Leading to Discontinuation Through Week 96(From Day 1 through Week 96)
- Mean Changes in Fasting Insulin at Week 96(Baseline (Day 1) and Week 96.)
- Number of Participants With Laboratory Abnormalities in Renal Function Test Through Week 96(At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.)
- Number of Participants With Laboratory Abnormalities in Urinalysis Through Week 96(At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.)
- Mean Percent Changes From Baseline in Limb, Trunk and Total Body Fat Measured by DEXA at Week 96(Baseline (Day 1) and Week 96.)
- Mean Percent Changes From Baseline in BMD Measured by DEXA at Week 96(Baseline (Day 1) and Week 96)
- Mean Change in Fasting Insulin at Week 48(Baseline (Day 1) and Week 48.)
- Mean Change From Baseline in Quality of Life as Measured by the Impact of Gastro-intestinal Toxicity at Week 24 Using the Irritable Bowel Syndrome Quality of Life (IBS-QoL)(Baseline (Day 1) and Week 24)
- Number of Participants With Laboratory Abnormalities in Hematology: Hemoglobin, Hematocrit, Platelet Count, INR, Neutrophils, PT and WBC Through Week 96(At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.)
- Mean Change From Baseline in Trunk-to-limb Fat Ratio Measured by DEXA at Week 48(DEXA scans were taken at Baseline (Day 1) and at Weeks 48.)
- Median Changes From Baseline at Week 96 in VAT-to-TAT, VAT-to-SAT and, Trunk-to-limb Fat Ratio Measured by Computed Tomography (CT)/DEXA(Baseline (Day 1) and Week 96.)
- Mean Change From Baseline in BMI at Week 96(Baseline (Day 1) and Week 96)
- Mean Change From Baseline in Waist Circumference at Week 48(Baseline (Day 1) and Week 48)
- Mean Change From Baseline in BMI at Week 48(Baseline (Day 1) and Week 48.)
- Reduction of log10 HIV RNA Levels From Baseline at Week 96(Baseline (Day 1) and Week 96)
- Mean Changes in Fasting Glucose at Week 96(Baseline (Day 1) and Week 96)
- Number of Participants With Laboratory Abnormalities in Serum Enzyme Levels Through Week 96(At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.)
- Number of Participants With Virologic Failure Showing Treatment Emergent Resistance Through Week 96(Baseline (Day 1) and Week 96.)
- Mean Percent Changes From Baseline in Bone Mineral Density (BMD) Measured by DEXA at Week 48(DEXA scans were taken at Baseline (Day 1) and Week 48.)
- Mean Change From Baseline in Body Weight at Week 48(Baseline (Day 1) and Week 48)
- Mean Change From Baseline in Waist-to-hip-ratio at Week 96(Baseline (Day 1) and Week 96)
- Mean Change From Baseline in Waist-to-hip-ratio at Week 48(Baseline (Day 1) and Week 48)
- Mean Changes From Baseline in Body Weight at Week 96(Physical examination was performed at Baseline (Day 1) and Weeks 48 and 96.)
- Mean Change From Baseline in Waist Circumference at Week 96(Baseline (Day 1) and Week 96.)