Renal Effect of Stribild or Other Tenofovir DF-containing Regimens Compared to Ritonavir-boosted Atazanavir Plus Abacavir/Lamivudine in Antiretroviral Treatment-naive HIV-1 Infected Adults
Condition: HIV-1 Infection
Intervention: STB; TVD; ATR; RTV; ATV; ABC/3TC; Iohexol
Intervention description: 150/150/200/300 mg fixed dose combination (FDC) tablet administered orally once daily with food; 200/300 mg FDC tablet administered orally once daily with food; 600/200/300 mg FDC tablet administered orally once daily on an empty stomach at bedtime; 100 mg tablet administered orally once daily with food; 300 mg capsule administered orally once daily with food; 600/300 mg FDC tablet administered orally once daily with food; 1500 mg solution administered intravenously at baseline, and at Weeks 4, 8, 16, and 24
Intervention MeSH terms: Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 72.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to assess glomerular function before and during
      administration of stribild (STB; elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil
      fumarate (E/C/F/TDF)) or a regimen containing TDF without cobicistat (COBI) as ritonavir
      (RTV)-boosted atazanavir (ATV/r) plus truvada (TVD; FTC/TDF) or atripla (ATR;
      efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF)) compared to a regimen
      containing neither TDF nor COBI as ATV/r plus abacavir/lamivudine (ABC/3TC) via determination
      of actual glomerular filtration rate (aGFR) using iohexol (a probe GFR marker) plasma
      clearance and estimated (calculated) glomerular filtration rate (eGFR).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Treatment naïve

          -  Plasma HIV-1 RNA levels ≥ 5,000 copies/mL at Screening

          -  CD4 cell count > 200 cells/µL

          -  Screening genotype report provided by the site must show sensitivity to FTC, TDF, EFV,
             ABC, 3TC, ATV and absence of study drug resistance mutations that include K65R, K70E
             and M184V in RT

          -  Estimated GFR ≥ 70 mL/min

          -  Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase
             [ALT]) ≤ 5 × upper limit of normal (ULN)

          -  Total bilirubin ≤ 1.5 mg/dL (≤ 26 umol/L), or normal direct bilirubin

          -  Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥
             50,000/mm^3; hemoglobin ≥ 8.5 g/dL)

          -  Serum amylase ≤ 5 × ULN (individuals with serum amylase > 5 × ULN will remain eligible
             if serum lipase is ≤ 5 × ULN)

          -  Normal electrocardiogram (ECG) or not clinically significant if abnormal ECG

          -  Not pregnant or non-lactating females of non-childbearing potential. Or females with
             childbearing potential who agree to utilize highly effective contraception methods or
             be non-heterosexually active or practice sexual abstinence from screening throughout
             the duration of study treatment and for 90 days if taking EFV/FTC/TDF or for 30 days
             for all other study drugs following the last study drug dose

          -  Males who agree to utilize a highly effective method of contraception during
             heterosexual intercourse or be non-heterosexually active, or practice sexual
             abstinence from first dose throughout the study period and for 90 days if taking
             EFV/FTC/TDF or for 30 days for all other study drugs following the last study drug
             dose. Males who agree to refrain from sperm donation from first dose until at least 90
             days if taking EFV/FTC/TDF or for 30 days for all other study drugs following the last
             study drug dose

          -  Body mass index (BMI) of 19 ≤ BMI ≤ 30 kg/m^2 and body weight ≥ 40 kg

          -  Life expectancy ≥ 1 year

        Key Exclusion Criteria:

          -  HLA-B*5701 allele positive

          -  A new AIDS-defining condition diagnosed within the 30 days prior to screening

          -  Hepatitis B surface antigen (HBsAg) positive

          -  Hepatitis C virus (HCV) antibody positive and HCV RNA detectable

          -  Individuals experiencing decompensated cirrhosis

          -  Females who are breastfeeding

          -  Positive serum pregnancy test

          -  Have an implanted defibrillator or pacemaker

          -  Current alcohol or substance that could potentially interfere with study compliance

          -  A history of malignancy within the past 5 years (prior to screening) or ongoing
             malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or
             resected, non-invasive cutaneous squamous carcinoma. Individuals with cutaneous KS are
             eligible, but must not have received any systemic therapy for KS within 30 days of Day
             1 Visit and must not be anticipated to require systemic therapy during the study

          -  Active, serious infections (other than HIV-1 infection) requiring parenteral
             antibiotic or antifungal therapy within 30 days prior to Day 1 Visit

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.