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

Gilead Sciences

Status and phase: Completed; Phase 4

Conditions: HIV-1 Infection

Treatments: Drug: ATV; Drug: RTV; Drug: ABC/3TC; Drug: ATR; Drug: TVD; Drug: STB; Drug: Iohexol

Study type: Interventional

Funder types: Industry

Identifiers

NCT02246998

2014-002095-93 (EudraCT Number)

GS-US-236-0140

Details and patient eligibility

About

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).

Enrollment: 72 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

72 participants in 4 patient groups

STB+iohexol

Experimental group

Description:

Participants will receive STB+iohexol for 24 weeks.

Treatment:

Drug: Iohexol

Drug: STB

RTV+ATV+TVD+iohexol

Experimental group

Description:

Participants will receive RTV+ATV+TVD+iohexol for 24 weeks.

Treatment:

Drug: Iohexol

Drug: TVD

Drug: RTV

Drug: ATV

ATR+iohexol

Experimental group

Description:

Participants will receive ATR+iohexol for 24 weeks.

Treatment:

Drug: Iohexol

Drug: ATR

RTV+ATV+ABC/3TC+iohexol

Experimental group

Description:

Participants will receive RTV+ATV+ABC/3TC+iohexol for 24 weeks.

Treatment:

Drug: Iohexol

Drug: ABC/3TC

Drug: RTV

Drug: ATV