Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
Condition: Acquired Immunodeficiency Syndrome; HIV Infections
MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes
Intervention: E/C/F/TDF; COBI; ATV; DRV; NRTI
Intervention description: E/C/F/TDF (150/150/200/300 mg) STR administered orally once daily; COBI 150 mg tablet administered with food orally once daily; ATV 300 mg tablet administered orally once daily; DRV 800 mg tablet administered orally once daily; Participants will receive 2 investigator-selected NRTIs, which may include abacavir (ABC), lamivudine (3TC)/zidovudine (ZDV), didanosine (DDI), emtricitabine (FTC), ABC/3TC, 3TC, tenofovir disoproxil fumarate (TDF), or FTC/TDF, administered according to prescribing information.
Intervention MeSH terms: Darunavir; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 106.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV-1; Treatment Naive; Treatment Experienced

Summary:

      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.
    

Eligibility criteria:

        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