open-label safety study of e/c/f/taf (genvoya®) in hiv-1 positive patients with mild to moderate renal impairment

Conditions: HIV; HIV Infections

Summary: the primary objective of this study is to evaluate the effect of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (e/c/f/taf) fixed-dose combination (fdc) tablet on renal parameters at week 24 in treatment-naive and treatment-experienced hiv-positive, adults with mild to moderate renal impairment.


Eligibility criteria:
key inclusion criteria: cohort 1 (treatment-experienced switch) * must not have a history of known resistance to elvitegravir (evg), tenofovir disoproxil fumarate (tdf), or emtricitabine (ftc) * plasma hiv-1 rna concentrations (at least two measurements) at undetectable levels (according to the local assay being used) in the 6 months preceding the screening visit and have hiv-1 rna \< 50 copies/ml at screening * estimated glomerular filtration rate (gfr) 30-69 ml/min according to the cockcroft-gault formula for creatinine clearance, using actual weight * may be currently enrolled in gilead studies gs-us-236-0102, gs-us-236-0103, and gs-us-216-0114, but will be eligible to enroll only after the week 144 visit for that study is complete; or currently receiving stribild® (stb) or atazanavir (atv)/cobicistat (cobi) + truvada (tvd) in gilead studies gs-us-236-0104 or gs-us-216-0105, but will be eligible to enroll only after the week 48 visit for that study is complete. cohort 2 (treatment-naive) * plasma hiv-1 rna levels ≥ 1,000 copies/ml at screening * screening genotype report provided by gilead sciences must show sensitivity to evg, ftc, and tdf * no prior use of any approved or investigational antiretroviral drug for any length of time, except the use for pre-exposure prophylaxis (prep), or post-exposure prophylaxis (pep), up to 6 months prior to screening * estimated gfr 30-69 ml/min according to the cockcroft gault formula for creatinine clearance, using actual weight all cohorts: all individuals must meet all of the following inclusion criteria to be eligible for participation in this study: * the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures * cd4+ count of ≥ 50 cells/μl * stable renal function: serum creatinine measurements to be taken at least once (within three months of screening) * cause of underlying chronic kidney disease (eg hypertension, diabetes) stable, without change in medical management, for 3 months prior to baseline * normal electrocardiogram (ecg) * hepatic transaminases (ast and alt) ≤ 5 x upper limit of normal (uln) * total bilirubin ≤ 1.5 mg/dl, or normal direct bilirubin * adequate hematologic function * serum amylase ≤ 5 x uln * females of childbearing potential must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence) from screening throughout the duration of study treatment and for 30 days following the last dose of study drug * females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing * males must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product. a highly effective method of contraception is defined as two separate forms of contraception, one of which must be an effective barrier method, or males must be non-heterosexually active, or practice sexual abstinence key exclusion criteria: * a new aids-defining condition (excluding cd4 cell count and percentage criteria) diagnosed within the 30 days prior to screening,with the exception of the first two bullet points * hepatitis c virus (hcv) antibody positive. individuals who are hcv positive, but have a documented negative hcv rna, are eligible * hepatitis b surface antigen (hbvsag) positive * individuals receiving drug treatment for hepatitis c, or individuals who are anticipated to receive treatment for hepatitis c during the course of the study * individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, etc.) * females who are breastfeeding * positive serum pregnancy test * have an implanted defibrillator or pacemaker * current alcohol or substance use judged by the investigator to potentially interfere with study compliance * a history of malignancy within the past 5 years or ongoing malignancy other than cutaneous kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma * active, serious infections (other than hiv-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline * individuals on hemodialysis, other forms of renal replacement therapy, or on treatment for underlying kidney diseases (including prednisolone and dexamethasone) * individuals receiving ongoing therapy with any medications not to be used with evg, cobi, ftc, or taf or individuals with any known allergies to the excipients of e/c/f/taf note: other protocol defined inclusion/exclusion criteria may apply.

Keywords: hiv hiv-1 infected treatment experienced treatment naive