HIV InfectionsPhase 3NCT00272779
BMS-Reyataz Study in Treatment in Naive Subjects to Compare the Efficacy and Safety Between Boosted Reyataz and Kaletra When in Combination With Fixed Dose Truvada
A Phase 3 study testing ATV, RTV and Tenofovi-Emtricitabine (TDF/FTC) tablet in people with HIV Infections, run by Bristol-Myers Squibb at 79 sites in 29 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- ATV, RTV and Tenofovi-Emtricitabine (TDF/FTC) tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,057 participants
- Where
- 79 sitesin 29 countries
- Study dates
- Nov 2005to Oct 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV RNA ≥5000 c/ml
Who cannot join
- 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;
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- 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.
Trial locations and contacts
79 sites in 29 countries.
79 sites in 29 countries
South Africa9 sites
Local Institution
Bloemfontein, Free State
Local Institution
Durban, KwaZulu-Natal
Local Institution
Johannesburg, Gauteng
Local Institution
Meadowdale, Gauteng
Local Institution
Mowbray, Western Cape
Local Institution
Parow, Western Cape
Local Institution
Port Elizabeth, Eastern Cape
Local Institution
Rugby, Western Cape
Local Institution
Westdene, Gauteng
United States8 sites
Local Institution
Dallas, Texas
Local Institution
Fort Lauderdale, Florida
Local Institution
Fort Worth, Texas
Local Institution
Huntersville, North Carolina
Local Institution
Laguna Beach, California
Local Institution
Orlando, Florida
Local Institution
Phoenix, Arizona
Local Institution
Washington D.C., District of Columbia
Mexico7 sites
Local Institution
Chihuaha
Local Institution
Durango
Local Institution
Guadalajara, Jalisco
Local Institution
Mexico City, Mexico City
Local Institution
San Luis Potisi
Local Institution
Zapopal, Jalisco
Local Institution
Zapopan, Jalisco
Argentina5 sites
Local Institution
Buenos Aires
Local Institution
Capital Federal, Buenos Aires
Local Institution
Córdoba
Local Institution
Mar del Plata, Buenos Aires
Local Institution
Rosario, Santa Fe Province
Brazil5 sites
Local Institution
Campinas, São Paulo
Local Institution
Curitiba, Paraná
Local Institution
Recife, Pernambuco
Local Institution
Rio de Janeiro
Local Institution
São Paulo
Germany4 sites
Local Institution
Berlin
Local Institution
Bonn
Local Institution
Cologne
Local Institution
Hamburg
Italy4 sites
Local Institution
Genova
Local Institution
Milan
Local Institution
Roma
Local Institution
Torino
Spain4 sites
Local Institution
Barcelona
Local Institution
Córdoba
Local Institution
Madrid
Local Institution
Málaga
Australia3 sites
Local Institution
Carlton, Victoria
Local Institution
Darlinghurst, New South Wales
Local Institution
South Yarra, Victoria
France3 sites
Local Institution
Nice
Local Institution
Paris
Local Institution
Villejuif
Canada2 sites
Local Institution
Montreal, Quebec
Local Institution
Toronto, Ontario
Chile2 sites
Local Institution
Santiago, Santiago Metropolitan
Local Institution
Viña del Mar, Valparaiso
United Kingdom2 sites
Local Institution
London, Greater London
Local Institution
Manchester, Greater Manchester
About this study
Official title: 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
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.
- Conditions
- HIV Infections
- Being tested
- ATV, RTV, Tenofovi-Emtricitabine (TDF/FTC) tablet, LPV
- Keywords
- HIV, Treatment Naive
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATVDrug
Also called Atazanavir, Reyataz, BMS-232632
300mg Oral capsules for 96 weeks
RTVDrug
100mg Oral Capsules for 96 weeks
Tenofovi-Emtricitabine (TDF/FTC) tabletDrug
One tablet with 300 mg - 200 mg once a day for 96 weeks.
LPVDrug
400 mg (3 133mg capsules) BID for 96 weeks
| Study group | Role | What they receive |
|---|---|---|
| Atazanavir (ATV) + Ritonovir (RTV) | Active comparator | 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. Receives: Drug: ATV; Drug: RTV; Drug: Tenofovi-Emtricitabine (TDF/FTC) tablet |
| Lopinavir (LPV) + RTV | Active comparator | 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. Receives: Drug: RTV; Drug: Tenofovi-Emtricitabine (TDF/FTC) tablet; Drug: LPV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Human-immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) < 50 Copies (c)/mL at 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.
Measured: Baseline (Day 1) and Week 48
Maximum Plasma Concentration (Cmax) of ATV/RTV and LPV/RTV in the Presence of an Antiretroviral (ARV) Regimen Including TDF at Week 4
Cmax was derived from plasma concentration versus time data.
Measured: 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.
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
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.
Measured: 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.
Minimum Plasma Concentration (Cmin) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4
Cmin was derived from the plasma concentration versus time data.
Measured: 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.
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
Tmax was derived from the plasma concentration versus time data.
Measured: 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.
Terminal Elimination Half-life (T-half) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4
T-half was derived from the plasma concentration versus time data.
Measured: 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.
Protein Binding Adjusted Effective Concentration (EC-90) of ATV and LPV When Dosed With RTV at Week 4
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).
Measured: 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.
Inhibitory Quotient (IQ) of ATV and LPV When Dosed With RTV at Week 4
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.
Measured: 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 of RTV at Week 4
Cmax was derived from plasma concentration versus time data.
Measured: 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) of RTV at Week 4
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.
Measured: 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 of RTV at Week 4
Cmin was derived from plasma concentration versus time data.
Measured: 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 of Tenofovir at Week 4
Cmax was derived from plasma concentration versus time data.
Measured: 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 of Tenofovir at Week 4
Cmin was derived from plasma concentration versus time data.
Measured: 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) of Tenofovir at Week 4
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.
Measured: 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.
Mean Change From Baseline in Trunk-to-Limb Fat Ratio as Measured by Dual Energy X-ray Absorptiometry (DEXA) at 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.
Measured: Baseline (Day 1) and Week 96.
Number of Participants With Single Nucleotide Polymorphisms (SNPs) Included in Genotype-Phenotype Analysis
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].
Measured: Baseline visit
Mean Change From Baseline in Fasting Non-High Density Lipoprotein (HDL) Cholesterol Associated With RETN_097
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.
Measured: Baseline (Day 1), Week 48, and Week 96.
Mean Change From Baseline in Fasting Triglycerides Associated With RETN_097
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.
Measured: Baseline (Day 1), Week 48, and Week 96.
Mean Change From Baseline in Fasting Triglycerides Associated With RETN_2265
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.
Measured: Baseline (Day 1), Week 48, and Week 96.
Mean Change From Baseline in Fasting Triglycerides Associated With RETN_598
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.
Measured: Baseline (Day 1), Week 48, and Week 96.
Mean Change From Baseline in Fasting Triglycerides Associated With APOE_C130R
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.
Measured: Baseline (Day 1), Week 48, and Week 96.
Mean Change From Baseline in Fasting Triglycerides Associated With RETN_734
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.
Measured: Baseline (Day 1), Week 48, and Week 96.
Mean Change From Baseline in Fasting Plasminogen Activator Inhibitor (PAI)-1 Associated With APOE_R176C
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.
Measured: Baseline (Day 1), Week 48, and Week 96.
Mean Change From Baseline in Fasting Tumor Necrosis Factor (TNF)-Alpha Associated With IL6_5309
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.
Measured: Baseline (Day 1), Week 48, and Week 96.
Mean Change From Baseline in Fasting Tumor Necrosis Factor (TNF)-Alpha Asssociated With RS11030679
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.
Measured: Baseline (Day 1), Week 48, and Week 96.
Mean Change From Baseline in Subcutaneous Adipose Tissue (SAT)-To-Trunk Adipose Tissue (TAT) Ratio Associated With CCDC122_5980
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).
Measured: Baseline (Day 1), Week 48, and Week 96.
Mean Change From Baseline in Visceral Adipose Tissue (VAT) Associated With BRUNOL_1842
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).
Measured: Baseline (Day 1), Week 48, and Week 96.
Mean Change From Baseline in VAT Associated With RETN_730
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).
Measured: Baseline (Day 1), Week 48, and Week 96.
Mean Change From Baseline in VAT-to-TAT Ratio Associated With CCDA122_5980
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).
Measured: Baseline (Day 1), Week 48, and Week 96.
Secondary outcomes (59)
Number of Participants With HIV RNA < 400 c/mL at Week 48
HIV RNA < 400 c/mL is a less stringent measure of viral suppression (highest threshold of assay) and indicates that a participant responded to treatment.
Measured: Baseline (Day 1) and Week 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)
TLOVR defines responders at Week 48 as participants with confirmed HIV RNA <400 c/mL through Week 48 without intervening virologic rebound or treatment discontinuation. Virologic rebound is defined as confirmed on-treatment HIV RNA <400 c/mL or last on-treatment HIV RNA <400 c/mL followed by discontinuation. Participants are considered failures in this analysis if they experienced virologic rebound at or before Week 48, discontinued before Week 48, never responded by Week 48, never received study therapy or had missing HIV RNA at Week 48 and beyond.
Measured: Baseline (Day 1) and Week 48
Reduction of log10 HIV RNA Levels From Baseline to Week 48
Changes from baseline in log10 HIV RNA levels were calculated.
Measured: Baseline (Day 1) and Week 48
Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48
Mean change from baseline in CD4 cell counts was determined.
Measured: Baseline (Day 1) and Week 48.
Treatment Emergent Resistance in Isolates From Participants With Virologic Failure at Week 48
Participants with virologic failure are those who never suppressed (HIV RNA <400 c/mL) and were on study through Week 48, or who rebounded to HIV RNA >= 400 c/mL and those who discontinued due to insufficient viral load response. IAS=International AIDS Society, PI=protease inhibitor, RTI=reverse transcription inhibitor, TAMS=Thymidine Analogue-Associated Mutations, NRTI=non-nucleotide reverse transcriptase inhibitor, M184V= Methionine-to-valine mutation at position 184 (in reverse transcription [RT] gene), FC=fold change
Measured: 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
AEs:new,untoward medical occurrences/worsening of pre-existing medical condition,drug-related or not.SAEs: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 cancer;or overdose.Discontinuation from study was due either to an AE or was conducted at the investigator's discretion.AEs represented here include SAEs, which are not included in the AE count represented in the AE xml upload section. As such, these numbers may not match.
Measured: From baseline (Day 1) to 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)
Hematology abnormalities were graded per modified World Health Organization (WHO) criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe). Grade 3 and 4 criteria were: Hemoglobin: Grade 3: 6.5-7.9 g/dL, Grade 4: <6.5 g/dL; Hematocrit: Grade 3: >=19.5 - 24%, Grade 4: <19.5%; platelet count: Grade 3: 20,000- 49, 999/ mm^3, Grade 4: <20,000/mm^3; INR: Grade 3 Absolute Neutrophil Count (ANC): Grade 3: >= 500 - <750/mm^3, Grade 4: <500/mm^3; PT: Grade 3: 1.51 - 3.0*ULN, Grade 4: >3*ULN; WBC: Grade 3: >=800 to <1000/mm^3, Grade 4: <80/mm^3.
Measured: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.
Number of Participants With Laboratory Abnormalities in Serum Enzymes Levels Through Week 48
Laboratory measurements marked as abnormal, as per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe). Grade 3 and 4 criteria in serum enzymes were: Creatine phosphokinase (CPK): Grade 3: 5.1 - 10.0 * upper limit of normal (ULN), Grade 4: >10* ULN; Lipase: Grade 3: 2.10 - 5.0* ULN, Grade 4: 5.0* ULN.
Measured: 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
Liver function tests abnormalities were graded as per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe), while albumin was graded as per National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE). Grade 3 and 4 criteria were: alanine aminotransferase (ALT), aspartate aminotransferase(AST), alkaline phosphatase: Grade 3: 5.1- 10*ULN, Grade 4: >10*ULN; direct and total bilirubin: Grade 3: 2.6- 5*ULN, Grade 4: >5*ULN, Albumin: Grade 3: <2g/dL.
Measured: 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
Renal function test abnormalities were graded as per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe). Grade 3 and 4 criteria were: Blood urea nitrogen (BUN): Grade 3: 5.1- 10*ULN, Grade 4: >10*ULN; Creatinine: Grade 3: 3.1 - 6*ULN, Grade 4: >6*ULN; low phosphorous (hypophosphatemia): Grade 3: 1.0- 1.4 mg/dL, Grade 4: <1.0mg/dL; high uric acid (hyperuricemia): Grade 3: 12.1 - 15.0 mg/dL, Grade 4: >15.0 mg/dL.
Measured: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, and 48.
Number of Participants With Laboratory Abnormalities in Electrolytes Through Week 48
Serum electrolytes abnormalities,graded per modified WHOcriteria.Ranges were:hypercarbia:Grade3:41-45milliequivalents(meq)/L,Grade4:>45meq/L;hypocarbia:Grade3:10-14 meq/L,Grade4:<10 meq/L;hypercalcemia:Grade3:12.6 - 13.5 mg/dL,Grade 4:>13.5 mg/dL;hypocalcemia:6.1-6.9mg/dL,Grade4:<6.1mg/dL;hyperchloremia:Grade 3: 121-125 meq/L,Grade4:>125meq/L;hypochloremia:Grade 3:80-84 meq/L,Grade4:<80meq/L;hyperkalemia:Grade3:6.6-7.0meq/L,Grade4:>7.0meq/L;hypokalemia:Grade3:2.0-2.4 meq/L,Grade4:<2.0meq/L;hypernatremia:Grade3:158-165 meq/L,Grade4:>165meq/L;hyponatremia:Grade 3:116-122 meq/L,Grade 4:115 meq/L.
Measured: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.
Number of Participants With Laboratory Abnormalities in Urinalysis Through Week 48
Laboratory measurements marked as abnormal, per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe), at any study time point. The following Grade 3 and 4 definitions specify the criteria for MAs in urinalysis: Proteinuria: Grade 3: 4= or >2-3.5 g loss/day, Grade 4: >3.5 g loss/day.
Measured: 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
Laboratory measurements marked as abnormal, as per National Cholesterol Education Program (NCEP)- Adult Treatment Panel (ATP)-III guided categories. The following definitions specify the criteria for MAs in fasting lipids: Total cholesterol: Grade 3: 240 - 300 mg/dL, Grade 4: >=240 mg/dL, triglycerides: Grade 3: 200 - <500 mg/dL, Grade 4: >=500 mg/dL.
Measured: 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
Laboratory measurements marked as abnormal, per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe), at any study time point. The following Grade 3 and 4 definitions specify the criteria for MAs in fasting glucose: hypoglycemia: Grade 3: 30-39 mg/dL, Grade 4: <30 mg/dL; hyperglycemia: 251-500 mg/dL, Grade 4: >500 mg/dL.
Measured: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.
Mean Change in Weight From Baseline at Week 48
Mean change in body weight from baseline was determined.
Measured: Baseline (Day 1) and Week 48
Mean Change in Body Mass Index (BMI) in Participants at Week 48
Mean change in BMI from baseline at Week 48 was determined.
Measured: Baseline (Day 1) and Week 48
Mean Change in Fasting Lipid at Week 48
Mean change from baseline in fasting lipids, for fasting total cholesterol, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, and triglycerides at Week 48 were determined.
Measured: Baseline (Day 1) and Week 48.
Mean Change in Fasting Glucose at Week 48
Mean change from baseline in fasting glucose at Week 48.
Measured: Baseline (Day 1) and Week 48.
Mean Change in Fasting Insulin at Week 48
Mean change from baseline in fasting insulin at Week 48.
Measured: 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 24
Medical Outcomes Study HIV Health Survey (MOS-HIV) is developed to assess a patient's health and functional status associated with HIV infection. The MOS-HIV questionnaire is applied to participants with adequate linguistic skills. The subscale and summary scores range from 0-100 with a higher score indicating better health.
Measured: Baseline (Day 1) and Week 24.
Mean Change From Baseline in Quality of Life as Measured by the Medical Outcomes Survey - Human Immunodeficiency Virus (MOS-HIV) at Week 48
MOS-HIV is developed to assess a participant's health and functional status associated with HIV infection. The questionnaire is applied to participants with adequate linguistic skills and consists of 35 items. The questionnaire derives an overall health score and 10 subscale scores (health transitions, pain, physical functioning, role functioning, social functioning, cognitive functioning, mental health, energy/fatigue, health distress and quality of life).The subscale and summary scores range from 0-100 with a higher score indicating better health.
Measured: 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)
The IBS-QoL questionnaire has 34 items and an overall score and 8 subscale scores: dysphoria,interference with activity,body image,health worry, food avoidance,social reaction,sexual, and relationships. Overall and subscores transformed to a 0-100 scale (0=lowest score, 100=highest possible score). Scores between these values represent the percentage of the total possible score achieved. Higher scores=better IBS-related QoL. A 14-point change from BL in IBS-QoL score in women with moderate to severe functional bowel disorders is a minimally important difference based on pain and satisfaction.
Measured: IBS-QoL is administered at baseline (Day 1) and Week 4.
Mean Change From Baseline in Quality of Life as Measured by the Impact of Gastro-intestinal Toxicity at Week 12 (IBS-QoL)
The IBS-QoL questionnaire has 34 items and an overall score and 8 subscale scores: dysphoria,interference with activity,body image,health worry, food avoidance,social reaction,sexual, and relationships. Overall and subscores transformed to a 0-100 scale (0=lowest score, 100=highest possible score). Scores between these values represent the percentage of the total possible score achieved. Higher scores=better IBS-related QoL. A 14-point change from BL in IBS-QoL score in women with moderate to severe functional bowel disorders is a minimally important difference based on pain and satisfaction.
Measured: IBS-QoL is administered at baseline (Day 1) and Week 12.
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)
The IBS-QoL questionnaire has 34 items and an overall score and 8 subscale scores: dysphoria,interference with activity,body image,health worry, food avoidance,social reaction,sexual, and relationships. Overall and subscores transformed to a 0-100 scale (0=lowest score, 100=highest possible score). Scores between these values represent the percentage of the total possible score achieved. Higher scores=better IBS-related QoL. A 14-point change from BL in IBS-QoL score in women with moderate to severe functional bowel disorders is a minimally important difference based on pain and satisfaction.
Measured: Baseline (Day 1) and Week 24
Number of Participants Who Adhered to Regimen as Measured by Multicenter AIDS Cohort Study Adherence Questionnaire (MACS) at Week 48
The MACS adherence questionnaire asks patients how many medication doses they missed during the previous day, 2 days, 3 days and 4 days. Adherence to regimen was defined as taking 100% of medicine (all doses and numbers of pills as prescribed for each medicine). This strict adherence cut-off was based on the guidelines stating that anything less than excellent adherence may result in a virus breakthrough and development of resistance.
Measured: Week 48
Number of Participants With HIV RNA < 50 c/mL) at Week 96
HIV RNA < 50 c/mL is the most stringent measure of viral suppression (lowest threshold of assay) and indicates that a participant has responded to treatment.
Measured: Baseline (Day 1) and Week 96
Number of Participants With HIV RNA < 400 c/mL) at Week 96
HIV RNA <400 c/mL is a less stringent measure of viral suppression (highest threshold of assay) and indicates that a participant has responded to treatment.
Measured: Baseline (Day 1) and Week 96
Reduction of log10 HIV RNA Levels From Baseline at Week 96
Changes from baseline in log10 HIV RNA levels were calculated.
Measured: Baseline (Day 1) and Week 96
Mean Change From Baseline in CD4 Cell Count at Week 96
Mean change from baseline in CD4 count among treated participants was determined.
Measured: 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
AEs:new,untoward medical occurrences/worsening of pre-existing medical condition,drug-related or not.SAEs: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 cancer;or overdose.Discontinuation from study was due either to an AE or was conducted at the investigator's discretion.AEs represented here include SAEs, which are not included in the AE count represented in the AE xml upload section. As such, these numbers may not match.
Measured: From Day 1 through Week 96
Mean Changes in Fasting Lipids at Week 96
Mean change from baseline in fasting lipids at Week 96 was determined.
Measured: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.
Mean Changes in Fasting Glucose at Week 96
Mean change from baseline in fasting glucose at Week 96 was determined.
Measured: Baseline (Day 1) and Week 96
Mean Changes in Fasting Insulin at Week 96
Mean change from baseline in fasting insulin at Week 96.
Measured: Baseline (Day 1) and Week 96.
Number of Participants With Laboratory Abnormalities in Hematology: Hemoglobin, Hematocrit, Platelet Count, INR, Neutrophils, PT and WBC Through Week 96
Hematology abnormalities were graded per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe). Grade 3 and 4 criteria were: Hemoglobin: Grade 3: 6.5-7.9 g/dL, Grade 4: <6.5 g/dL; Hematocrit: Grade 3: >=19.5 - 24%, Grade 4: <19.5%; platelet count: Grade 3: 20,000- 49, 999/ mm^3, Grade 4: <20,000/mm^3; INR: Grade 3 Absolute Neutrophil Count (ANC): Grade 3: >= 500 - <750/mm^3, Grade 4: <500/mm^3; PT: Grade 3: 1.51 - 3.0*ULN, Grade 4: >3*ULN; WBC: Grade 3: >=800 to <1000/mm^3, Grade 4: <80/mm^3.
Measured: 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 Serum Enzyme Levels Through Week 96
Laboratory measurements marked as abnormal, as per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe). Grade 3 and 4 criteria in serum enzymes were: CPK: Grade 3: 5.1 - 10.0 * ULN, Grade 4: >10* ULN; Lipase: Grade 3: 2.10 - 5.0* ULN, Grade 4: 5.0* ULN.
Measured: 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 Liver Function Test Through Week 96
Liver function tests abnormalities were graded as per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe), while albumin was graded as per NCI-CTCAE. Grade 3 and 4 criteria were: ALT, AST, alkaline phosphatase: Grade 3: 5.1- 10*ULN, Grade 4: >10*ULN; direct and total bilirubin: Grade 3: 2.6- 5*ULN, Grade 4: >5*ULN, Albumin: Grade 3: <2g/dL.
Measured: 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 Renal Function Test Through Week 96
Renal function test abnormalities were graded as per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe). Grade 3 and 4 criteria were: BUN: Grade 3: 5.1- 10*ULN, Grade 4: >10*ULN; Creatinine: Grade 3: 3.1 - 6*ULN, Grade 4: >6*ULN; low phosphorous (hypophosphatemia): Grade 3: 1.0- 1.4 mg/dL, Grade 4: <1.0mg/dL; high uric acid (hyperuricemia): Grade 3: 12.1 - 15.0 mg/dL, Grade 4: >15.0 mg/dL.
Measured: 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
Serum electrolytes abnormalities,graded per modified WHOcriteria.Ranges were:hypercarbia:Grade3:41-45milliequivalents(meq)/L,Grade4:>45meq/L;hypocarbia:Grade3:10-14 meq/L,Grade4:<10 meq/L;hypercalcemia:Grade3:12.6 - 13.5 mg/dL,Grade 4:>13.5 mg/dL;hypocalcemia:6.1-6.9mg/dL,Grade4:<6.1mg/dL;hyperchloremia:Grade 3: 121-125 meq/L,Grade4:>125meq/L;hypochloremia:Grade 3:80-84 meq/L,Grade4:<80meq/L;hyperkalemia:Grade3:6.6-7.0meq/L,Grade4:>7.0meq/L;hypokalemia:Grade3:2.0-2.4 meq/L,Grade4:<2.0meq/L;hypernatremia:Grade3:158-165 meq/L,Grade4:>165meq/L;hyponatremia:Grade 3:116-122 meq/L,Grade 4:115 meq/L.
Measured: 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
Laboratory measurements marked as abnormal, as per NCEP-ATP-III guided categories. The following definitions specify the criteria for MAs in fasting lipids: Total cholesterol: Grade 3: 240 - 300 mg/dL, Grade 4: >=240 mg/dL, triglycerides: Grade 3: 200 - <500 mg/dL, Grade 4: >=500 mg/dL.
Measured: 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
Laboratory measurements marked as abnormal, per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe), at any study time point. The following Grade 3 and 4 definitions specify the criteria for MAs in fasting glucose: hypoglycemia: Grade 3: 30-39 mg/dL, Grade 4: <30 mg/dL; hyperglycemia: 251-500 mg/dL, Grade 4: >500 mg/dL.
Measured: 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
Laboratory measurements marked as abnormal, per modified WHO criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = very severe), at any study time point. The following Grade 3 and 4 definitions specify the criteria for MAs in urinalysis: Proteinuria: Grade 3: 4= or >2-3.5 g loss/day, Grade 4: >3.5 g loss/day.
Measured: 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
Virologic failure participants defined as participants who were never suppressed (HIV RNA < 400 c/mL) and on study through Week 48, or who rebounded to HIV RNA ≥ 400 c/mL, and those who discontinued due to insufficient viral load response using CVR (NC=F). IAS-USA=International AIDS Society-United States of America, PI=protease inhibitor, RTI=reverse transcription inhibitor, TAMS=Thymidine Analogue-Associated Mutations, NRTI=non-nucleotide reverse transcriptase inhibitor, M184/V= Methionine-to-valine mutation at position 184 (in reverse transcription [RT] gene), FC=fold change
Measured: Baseline (Day 1) and Week 96.
Mean Change From Baseline in Trunk-to-limb Fat Ratio Measured by DEXA at Week 48
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 was associated with a decrease in values.
Measured: DEXA scans were taken at Baseline (Day 1) and at Weeks 48.
Mean Percent Changes From Baseline in Limb, Trunk and Total Body Fat Measured by DEXA at Week 48
The mean percent change from baseline in limb, trunk and total body fat was measured by DEXA. Limb fat: a physical sign of lipoatrophy, clinical improvement in limb fat is associated with a decrease in values. Trunk fat: a physical sign of lipohypertrophy, clinical improvement in trunk fat is associated with a decrease in values. Total body fat: association of many factors like trunk fat, limb fat, weight etc. Clinical improvement in total body fat cannot be predicted based solely an increase or decrease of these values.
Measured: DEXA scans were performed at baseline (within 30 days of starting study treatment), and at Weeks 48.
Mean Percent Changes From Baseline in Limb, Trunk and Total Body Fat Measured by DEXA at Week 96
The mean percent change from baseline in limb, trunk and total body fat was measured by DEXA. Limb fat: a physical sign of lipoatrophy, clinical improvement in limb fat is associated with a decrease in values. Trunk fat: physical sign of lipohypertrophy, clinical improvement in trunk fat is associated with a decrease in values. Total body fat: association of many factors like trunk fat, limb fat, weight etc. Clinical improvement in total body fat cannot be predicted based solely an increase or decrease of these values.
Measured: Baseline (Day 1) and Week 96.
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
Measured: Baseline (Day 1) and Week 96.
Mean Percent Changes From Baseline in Bone Mineral Density (BMD) Measured by DEXA at Week 48
Mean percent change from baseline in BMD of arms, legs, trunk and total body was measured using DEXA, an X-ray scan technique.
Measured: DEXA scans were taken at Baseline (Day 1) and Week 48.
Mean Percent Changes From Baseline in BMD Measured by DEXA at Week 96
Mean percent change from baseline in BMD of arms, legs, trunk and total body was measured using DEXA, an X-ray scan technique.
Measured: Baseline (Day 1) and Week 96
Mean Change From Baseline in Body Weight at Week 96
Mean change from baseline in weight at Week 96
Measured: Baseline (Day 1) and Week 96
Mean Change From Baseline in Body Weight at Week 48
Mean change from baseline in body weight at Week 48 was determined.
Measured: Baseline (Day 1) and Week 48
Mean Change From Baseline in BMI at Week 96
Measured: Baseline (Day 1) and Week 96
Mean Change From Baseline in Waist Circumference at Week 96
Mean change From baseline in waist circumference at Week 96 was determined.
Measured: Baseline (Day 1) and Week 96.
Mean Change From Baseline in Waist Circumference at Week 48
Mean change from baseline in waist circumference at Week 48 was determined.
Measured: Baseline (Day 1) and Week 48
Mean Change From Baseline in Waist-to-hip-ratio at Week 96
Mean change from baseline in waist-to-hip-ratio at Week 96 was determined.
Measured: Baseline (Day 1) and Week 96
Mean Change From Baseline in BMI at Week 48
Mean change from baseline in BMI at Week 48 was determined.
Measured: Baseline (Day 1) and Week 48.
Mean Change From Baseline in Waist-to-hip-ratio at Week 48
Mean change from baseline in waist-to-hip-ratio at Week 48 was determined.
Measured: Baseline (Day 1) and Week 48
Percentage of Participants With Lipoatrophy at Week 96
Lipoatrophy, redistribution of body fat was defined as >= 20% decrease in limb fat. The percentage of participants with lipoatrophy from baseline was determined.
Measured: Baseline (Day 1) and Week 96
Mean Changes From Baseline in Body Weight at Week 96
Mean change in body weight from baseline was determined.
Measured: Physical examination was performed at Baseline (Day 1) and Weeks 48 and 96.
Mean Change From Baseline in BMI at Week 96
Mean change From baseline in BMI at Week 96 was determined.
Measured: Baseline (Day 1) and Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2006 (estimated)
- Study startNov 2005
- Primary completionJun 2007
- Study completionOct 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,057 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00272779
- Sponsor's protocol ID
- AI424-138
- Status last verified
- Apr 2011
- First submitted
- 5 Jan 2006
- Last updated
- 9 May 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, Moyle G, Mancini M, Percival L, Yang R, Wirtz V, Lataillade M, Absalon J, McGrath D; CASTLE Study Team. Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study. J Acquir Immune Defic Syndr. 2010 Mar;53(3):323-32. doi: 10.1097/QAI.0b013e3181c990bf.
PubMed 20032785Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, Moyle G, Mancini M, Percival L, Yang R, Thiry A, McGrath D; CASTLE Study Team. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet. 2008 Aug 23;372(9639):646-55. doi: 10.1016/S0140-6736(08)61081-8.
PubMed 18722869Zhu L, Liao S, Child M, Zhang J, Persson A, Sevinsky H, Eley T, Xu X, Krystal M, Farajallah A, McGrath D, Molina JM, Bertz R. Pharmacokinetics and inhibitory quotient of atazanavir/ritonavir versus lopinavir/ritonavir in HIV-infected, treatment-naive patients who participated in the CASTLE Study. J Antimicrob Chemother. 2012 Feb;67(2):465-8. doi: 10.1093/jac/dkr490. Epub 2011 Nov 25.
PubMed 22121190Uy J, Yang R, Wirtz V, Sheppard L, Farajallah A, McGrath D. Treatment of advanced HIV disease in antiretroviral-naive HIV-1-infected patients receiving once-daily atazanavir/ritonavir or twice-daily lopinavir/ritonavir, each in combination with tenofovir disoproxil fumarate and emtricitabine. AIDS Care. 2011 Nov;23(11):1500-4. doi: 10.1080/09540121.2011.565033. Epub 2011 Jul 7.
PubMed 21732894Squires KE, Johnson M, Yang R, Uy J, Sheppard L, Absalon J, McGrath D. Comparative gender analysis of the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir at 96 weeks in the CASTLE study. J Antimicrob Chemother. 2011 Feb;66(2):363-70. doi: 10.1093/jac/dkq457. Epub 2010 Dec 9.
PubMed 21148235
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00272779
- Acronym / sponsor ID
- AI424-138
- Conditions
- HIV Infections
- Keywords
- HIV, Treatment Naive
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,057 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Nov 2005
- Primary completion
- Jun 2007 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 9 Jan 2006 (estimated)
- Results
- Posted 9 May 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Atazanavir (ATV) + Ritonovir (RTV) | Active comparator | Drug: ATV, Drug: RTV, Drug: Tenofovi-Emtricitabine (TDF/FTC) tabletParticipants 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. |
| Lopinavir (LPV) + RTV | Active comparator | Drug: RTV, Drug: Tenofovi-Emtricitabine (TDF/FTC) tablet, Drug: LPVParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- HIV RNA ≥5000 c/ml
Key exclusion criteria (28 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ATVAlso: Atazanavir, Reyataz, BMS-232632300mg Oral capsules for 96 weeks | Drug | Atazanavir (ATV) + Ritonovir (RTV) |
| RTV100mg Oral Capsules for 96 weeks | Drug | Atazanavir (ATV) + Ritonovir (RTV), Lopinavir (LPV) + RTV |
| Tenofovi-Emtricitabine (TDF/FTC) tabletOne tablet with 300 mg - 200 mg once a day for 96 weeks. | Drug | Atazanavir (ATV) + Ritonovir (RTV), Lopinavir (LPV) + RTV |
| LPV400 mg (3 133mg capsules) BID for 96 weeks | Drug | Lopinavir (LPV) + RTV |
Primary outcome
Number of Participants With Human-immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) < 50 Copies (c)/mL at Week 48
Time frame: 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.
Maximum Plasma Concentration (Cmax) of ATV/RTV and LPV/RTV in the Presence of an Antiretroviral (ARV) Regimen Including TDF at Week 4
Time frame: 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.
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
Time frame: 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.
Minimum Plasma Concentration (Cmin) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4
Time frame: 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.
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
Time frame: 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.
Terminal Elimination Half-life (T-half) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4
Time frame: 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.
Protein Binding Adjusted Effective Concentration (EC-90) of ATV and LPV When Dosed With RTV at Week 4
Time frame: 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).
Inhibitory Quotient (IQ) of ATV and LPV When Dosed With RTV at Week 4
Time frame: 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.
Cmax of RTV at Week 4
Time frame: 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 (0-24) of RTV at Week 4
Time frame: 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 RTV at Week 4
Time frame: 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.
Cmax of Tenofovir at Week 4
Time frame: 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.
Cmin of Tenofovir at Week 4
Time frame: 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.
AUC (TAU) of Tenofovir at Week 4
Time frame: 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 Trunk-to-Limb Fat Ratio as Measured by Dual Energy X-ray Absorptiometry (DEXA) at Week 96
Time frame: 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.
Number of Participants With Single Nucleotide Polymorphisms (SNPs) Included in Genotype-Phenotype Analysis
Time frame: 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].
Mean Change From Baseline in Fasting Non-High Density Lipoprotein (HDL) Cholesterol Associated With RETN_097
Time frame: 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_097
Time frame: 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_2265
Time frame: 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_598
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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 Subcutaneous Adipose Tissue (SAT)-To-Trunk Adipose Tissue (TAT) Ratio Associated With CCDC122_5980
Time frame: 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).
Mean Change From Baseline in Visceral Adipose Tissue (VAT) Associated With BRUNOL_1842
Time frame: 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
Time frame: 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
Time frame: 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).
59 secondary outcomes
Number of Participants With HIV RNA < 400 c/mL at Week 48
Time frame: Baseline (Day 1) and Week 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)
Time frame: Baseline (Day 1) and Week 48
Reduction of log10 HIV RNA Levels From Baseline to Week 48
Time frame: Baseline (Day 1) and Week 48
Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48
Time frame: Baseline (Day 1) and Week 48.
Treatment Emergent Resistance in Isolates From Participants With Virologic Failure at Week 48
Time frame: 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
Time frame: From baseline (Day 1) to 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)
Time frame: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.
Number of Participants With Laboratory Abnormalities in Serum Enzymes Levels Through Week 48
Time frame: 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
Time frame: 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
Time frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, and 48.
Number of Participants With Laboratory Abnormalities in Electrolytes Through Week 48
Time frame: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.
Number of Participants With Laboratory Abnormalities in Urinalysis Through Week 48
Time frame: 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
Time frame: 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
Time frame: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.
Mean Change in Weight From Baseline at Week 48
Time frame: Baseline (Day 1) and Week 48
Mean Change in Body Mass Index (BMI) in Participants at Week 48
Time frame: Baseline (Day 1) and Week 48
Mean Change in Fasting Lipid at Week 48
Time frame: Baseline (Day 1) and Week 48.
Mean Change in Fasting Glucose at Week 48
Time frame: Baseline (Day 1) and Week 48.
Mean Change in Fasting Insulin at Week 48
Time frame: 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 24
Time frame: Baseline (Day 1) and Week 24.
Mean Change From Baseline in Quality of Life as Measured by the Medical Outcomes Survey - Human Immunodeficiency Virus (MOS-HIV) at Week 48
Time frame: 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)
Time frame: IBS-QoL is administered at baseline (Day 1) and Week 4.
Mean Change From Baseline in Quality of Life as Measured by the Impact of Gastro-intestinal Toxicity at Week 12 (IBS-QoL)
Time frame: IBS-QoL is administered at baseline (Day 1) and Week 12.
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)
Time frame: Baseline (Day 1) and Week 24
Number of Participants Who Adhered to Regimen as Measured by Multicenter AIDS Cohort Study Adherence Questionnaire (MACS) at Week 48
Time frame: Week 48
Number of Participants With HIV RNA < 50 c/mL) at Week 96
Time frame: Baseline (Day 1) and Week 96
Number of Participants With HIV RNA < 400 c/mL) at Week 96
Time frame: Baseline (Day 1) and Week 96
Reduction of log10 HIV RNA Levels From Baseline at Week 96
Time frame: Baseline (Day 1) and Week 96
Mean Change From Baseline in CD4 Cell Count at Week 96
Time frame: 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
Time frame: From Day 1 through Week 96
Mean Changes in Fasting Lipids at Week 96
Time frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.
Mean Changes in Fasting Glucose at Week 96
Time frame: Baseline (Day 1) and Week 96
Mean Changes in Fasting Insulin at Week 96
Time frame: Baseline (Day 1) and Week 96.
Number of Participants With Laboratory Abnormalities in Hematology: Hemoglobin, Hematocrit, Platelet Count, INR, Neutrophils, PT and WBC Through Week 96
Time frame: 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 Serum Enzyme Levels Through Week 96
Time frame: 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 Liver Function Test Through Week 96
Time frame: 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 Renal Function Test Through Week 96
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20032785Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, Moyle G, Mancini M, Percival L, Yang R, Wirtz V, Lataillade M, Absalon J, McGrath D; CASTLE Study Team. Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study. J Acquir Immune Defic Syndr. 2010 Mar;53(3):323-32. doi: 10.1097/QAI.0b013e3181c990bf.
- Background: PubMed 18722869Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, Moyle G, Mancini M, Percival L, Yang R, Thiry A, McGrath D; CASTLE Study Team. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet. 2008 Aug 23;372(9639):646-55. doi: 10.1016/S0140-6736(08)61081-8.
- Derived from this study: PubMed 22121190Zhu L, Liao S, Child M, Zhang J, Persson A, Sevinsky H, Eley T, Xu X, Krystal M, Farajallah A, McGrath D, Molina JM, Bertz R. Pharmacokinetics and inhibitory quotient of atazanavir/ritonavir versus lopinavir/ritonavir in HIV-infected, treatment-naive patients who participated in the CASTLE Study. J Antimicrob Chemother. 2012 Feb;67(2):465-8. doi: 10.1093/jac/dkr490. Epub 2011 Nov 25.
- Derived from this study: PubMed 21732894Uy J, Yang R, Wirtz V, Sheppard L, Farajallah A, McGrath D. Treatment of advanced HIV disease in antiretroviral-naive HIV-1-infected patients receiving once-daily atazanavir/ritonavir or twice-daily lopinavir/ritonavir, each in combination with tenofovir disoproxil fumarate and emtricitabine. AIDS Care. 2011 Nov;23(11):1500-4. doi: 10.1080/09540121.2011.565033. Epub 2011 Jul 7.
- Derived from this study: PubMed 21148235Squires KE, Johnson M, Yang R, Uy J, Sheppard L, Absalon J, McGrath D. Comparative gender analysis of the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir at 96 weeks in the CASTLE study. J Antimicrob Chemother. 2011 Feb;66(2):363-70. doi: 10.1093/jac/dkq457. Epub 2010 Dec 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
79 sites in 29 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ATV, RTV and Tenofovi-Emtricitabine (TDF/FTC) tablet in people with HIV Infections, run by Bristol-Myers Squibb at 79 sites in 29 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 79 sites in South Africa, United States, Mexico, Argentina, Brazil and 24 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Human-immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) < 50 Copies (c)/mL at Week 48 (time frame: Baseline (Day 1) and Week 48). The study lists 29 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00272779, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2011.