Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment

Gilead Sciences

Status and phase: Completed; Phase 3

Conditions: HIV Infections; Acquired Immunodeficiency Syndrome

Treatments: Drug: ATV; Drug: E/C/F/TDF; Drug: DRV; Drug: NRTI; Drug: COBI

Study type: Interventional

Funder types: Industry

Identifiers

NCT01363011

GS-US-236-0118

Details and patient eligibility

About

This study is to characterize the effect of cobicistat-based regimens on parameters of renal function in participants with HIV infection and who have mild to moderate renal impairment, and to assess the safety and tolerability of the regimens in order to generate appropriate dosing recommendations.

Enrollment: 106 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Cohort 1 (treatment-naive)

• Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening
• Screening genotype report must show sensitivity to FTC and TDF
• No prior use of any approved or investigational antiretroviral drug for any length of time

Cohort 2 (treatment-experienced, pharmacoenhancer switch)

• Subjects must be receiving ATV 300 mg/ritonavir (RTV) 100 mg plus 2 NRTIs OR DRV 800 mg/RTV 100 mg plus 2 NRTIs for at least 6 months prior to screening
• Plasma HIV-1 RNA concentrations at undetectable levels in the 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at screening
• Subjects experiencing intolerance to RTV (as determined by the investigator)

Both groups

• The ability to understand and sign a written informed consent form
• Normal ECG
• Mild to moderate renal function
• Stable renal function
• Hepatic transaminases (AST and ALT) ≤ 5 x the upper limit of the normal range (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (subjects with documented Gilbert's Syndrome or hyperbilirubinemia due to atazanavir therapy may have total bilirubin up to 5 x ULN)
• Adequate hematologic function
• Serum amylase ≤ 5 x ULN
• Males and females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drug
• Age ≥ 18 years

Exclusion criteria

• New AIDS-defining condition diagnosed within the 30 days prior to screening
• Receiving drug treatment for hepatitis C, or anticipated to receive treatment for hepatitis C
• Subjects experiencing decompensated cirrhosis
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Implanted defibrillator or pacemaker
• Current alcohol or substance use judged by the investigator to potentially interfere with subject study compliance
• History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
• Receiving ongoing therapy with any of medications contraindicated for use with elvitegravir (EVG), COBI, FTC, TDF, ATV, DRV; or subjects with any known allergies to the excipients of E/C/F/TDF STR, COBI tablets, ATV capsules or DRV tablets or contraindicated for the 2 NRTIs as part of the PI/co regimen
• Participation in any other clinical trial without prior approval
• Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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106 participants in 2 patient groups

E/C/F/TDF (Cohort 1)

Experimental group

Description:

Participants who have not received prior antiretroviral (ARV) treatment and who are virologically unsuppressed at baseline will initiate treatment with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) single-tablet regimen (STR) for up to 96 weeks. Following Week 96, participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country.

Treatment:

Drug: E/C/F/TDF

COBI+PI+2 NRTI (Cohort 2)

Experimental group

Description:

Participants who have received prior ARV treatment and who are virologically suppressed at baseline will continue their treatment regimen, switching the regimen's pharmacoenhancer component from ritonavir to cobicistat (COBI), and continuing their existing protease inhibitor (PI; either atazanavir (ATV) or darunavir (DRV)) plus 2 nucleoside reverse transcriptase inhibitor (NRTI) regimen for up to 96 weeks. Following Week 96, participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country.

Treatment:

Drug: COBI

Drug: DRV

Drug: NRTI

Drug: ATV