A Prospective, Randomized, Open Label Phase IV Study to Evaluate the Rationale of Switching From Fixed Dose Abacavir (ABC)/Lamivudine (3TC) to Fixed Dose Tenofovir DF (TDF)/Emtricitabine (FTC) in Virologically Suppressed, HIV-1 Infected Patients Maintained on a Ritonavir Boosted Protease Inhibitor Containing Antiretroviral Regimen
Overview
- Phase
- Phase 4
- Intervention
- emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)
- Conditions
- HIV Infection
- Sponsor
- Gilead Sciences
- Enrollment
- 312
- Locations
- 80
- Primary Endpoint
- Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) < 200 Copies/mL Through Week 48 Based on Time to Loss of Virologic Response (TLOVR) Algorithm
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
This protocol describes a prospective, randomized, open-label, multicenter study to evaluate the safety and efficacy of switching from fixed dose abacavir (ABC)/lamivudine (3TC) to fixed dose emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in virologically suppressed, human immunodeficiency virus type 1 (HIV-1) infected subjects maintained on a ritonavir-boosted protease inhibitor (PI/r)-containing antiretroviral (ARV) regimen. Duration of treatment is 48 weeks.
Detailed Description
This protocol describes a prospective, randomized, open-label, multicenter study to evaluate the safety and efficacy of switching from fixed dose ABC/3TC to fixed dose FTC/TDF in virologically suppressed, HIV-1 infected subjects maintained on a PI/r-containing ARV regimen. Subjects were stratified based on the PI/r (ie, lopinavir/ritonavir \[LPV/r\] versus other boosted PIs) in their regimen, and the presence versus absence of comorbidities at screening (diabetes mellitus or cardiovascular disease such as hypertension, coronary artery disease, hyperlipidemia, history of myocardial infarction, cardiomyopathy, valvular heart disease, congenital heart disease, stroke, peripheral vascular disease, or arrhythmias). Subjects were randomized 1:1 to switch to FTC/TDF+PI/r or to continue on their existing regimen. Subjects received study treatment for 48 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adult (greater than or equal to 18 years) males or non-pregnant, non-lactating females
- •HIV-1 infected subjects currently receiving a ritonavir-boosted protease inhibitor and fixed-dose ABC/3TC regimen continuously for greater than or equal to 3 months
- •HIV infection as documented by a validated HIV antibody enzyme-linked immunosorbent assay (ELISA) and confirmed by one of the following:
- •Immunoblot detection of HIV antibody
- •Positive HIV-1 blood culture
- •Positive HIV-1 serum P24 antigen
- •HIV-1 plasma viremia greater than 1000 copies/mL by polymerase chain reaction (PCR) or branched-chain deoxyribonucleic acid (bDNA) method
- •Detection of proviral DNA by PCR
- •(If confirmation of HIV infection is not available then repeat testing of HIV antibody will be required)
- •Two consecutive plasma HIV-1 RNA concentration less than 200 copies/mL. The two HIV-1 RNA determinations ensure that the subject has been virologically-suppressed for at least 3 months prior to study entry:
Exclusion Criteria
- •Subjects receiving ABC/3TC and a PI without ritonavir
- •Subjects receiving other ARV agents (eg, 2 protease inhibitors boosted with low-dose ritonavir (ie, "double-boosted PI regimens"), nonnucleoside reverse transcriptase inhibitors \[NNRTIs\], integrase inhibitors, TDF, or other nucleoside reverse transcriptase inhibitor \[NRTIs\]) in addition to ABC/3TC and a ritonavir-boosted protease inhibitor
- •Have known resistance to any of the study agents at any time in the past including NRTI resistance mutations (including but not limited to K65R, L74V/I, M184V/I, or thymidine analog mutations) and/or PI resistance mutations
- •A new acquired immunodeficiency syndrome (AIDS) defining condition diagnosed (with the exception of CD4 criteria) within 30 days of baseline
- •Previous therapy with agents with systemic myelosuppressive, pancreatoxic, hepatotoxic or cytotoxic potential within 3 months of study start or the expected need for such therapy at the time of enrollment
- •Proven or suspected acute hepatitis in the 30 days prior to study entry
- •Anticipated need to initiate drugs during the study that are contraindicated with protease inhibitors (except upon approval by Gilead)
- •Receiving ongoing therapy with any of the following (administration of any of the following medications must be discontinued at least 30 days prior to the Baseline visit and for the duration of the study period):
- •Nephrotoxic agents (aminoglycoside antibiotics, amphotericin B, cidofovir, cisplatin, foscarnet, intravenous pentamidine, other agents with significant nephrotoxic potential)
- •Adefovir dipivoxil
Arms & Interventions
FTC/TDF (Truvada [TVD]) + PI/r
Participants in this group received fixed-dose combination FTC 200 mg/TDF 300 mg (Truvada \[TVD\]) for 48 weeks. The prestudy ritonavir-boosted PI was continued unmodified through the 48 weeks of the study.
Intervention: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)
ABC/3TC + PI/r
Participants in this group continued their prestudy therapy - ABC 600 mg/3TC 300 mg administered as one tablet orally once daily (Epzicom) plus ritonavir-boosted PI regimen, given orally for 48 weeks.
Intervention: abacavir (ABC)/lamivudine (3TC)
Outcomes
Primary Outcomes
Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) < 200 Copies/mL Through Week 48 Based on Time to Loss of Virologic Response (TLOVR) Algorithm
Time Frame: Baseline to 48 weeks
The percentage of participants with HIV-1 RNA \< 200 copies/mL based on TLOVR algorithm at Week 48 was summarized. Participants were considered nonresponders in the TLOVR analysis if they experienced virologic rebound prior to or at Week 48, discontinued study before Week 48, or added a new antiretroviral (ARV) agent prior to completion of the study. Virologic rebound was defined as 2 consecutive HIV-1 RNA values \>= 200 copies/mL or the last HIV-1 RNA value \>= 200 copies/mL followed by discontinuation from the study.
Secondary Outcomes
- Change From Baseline Fasting Glucose at Week 48(Baseline to 48 weeks)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48(48 weeks)
- Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 48(Baseline to 48 weeks)
- Change From Baseline Calculated Creatinine Clearance (CLcr) Using Ideal Body Weight by Cockcroft-Gault Method at Week 48(Baseline to 48 weeks)
- Change From Baseline Estimated Glomerular Filtration Rate (eGFR) by Modified Diet in Renal Disease (MDRD) at Week 48(Baseline to 48 weeks)
- Percentage of Participants With Pure Virologic Response (PVR) for HIV-1 RNA Cutoff at 200 Copies/mL Through Week 48(Baseline to 48 weeks)
- Percentage of Participants With Pure Virologic Response (PVR) for HIV-1 RNA Cutoff at 50 Copies/mL Through Week 48(Baseline to 48 weeks)
- Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Week 48(48 weeks)
- Change From Baseline Fasting Lipid Parameters at Week 48(Baseline to 48 weeks)
- Change From Baseline Ratio of Fasting Total Cholesterol Over High-density Lipoprotein (HDL) Cholesterol at Week 48(Baseline to 48 weeks)
- Change From Baseline C-Reactive Protein at Week 48(Baseline to 48 weeks)
- Change From Baseline Fibrinogen at Week 48(Baseline to 48 weeks)
- Change From Baseline Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor Necrosis Factor-alpha (TNF-alpha) at Week 48(Baseline to 48 weeks)