phase 3 open-label study to evaluate switching from optimized stable antiretroviral regimens containing darunavir to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (e/c/f/taf) fixed dose combination (fdc) plus darunavir (drv) in treatment experienced hiv-1 positive adults

Conditions: HIV-1; HIV Infections; Acquired Immunodeficiency Syndrome

Summary: the primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (e/c/f/taf) fixed dose combination (fdc) plus darunavir (drv) relative to current antiretroviral regimens (arv) in virologically suppressed, hiv-1 positive participants with hiv-1 rna \<50 copies/ml at week 24. this study consists of 48 weeks of open-label phase followed by an optional extension phase in which all the participants will receive e/c/f/taf+drv.


Eligibility criteria:
key inclusion criteria: * ability to understand and sign a written informed consent form * history of at least two prior antiretroviral regimens, and history of resistance to at least two different classes of antiretroviral agents * plasma hiv-1 rna levels \< 50 copies/ml at screening. virologically suppressed on the current antiretroviral regimen containing darunavir 600 mg twice a day or 800 mg once daily continuously for ≥ 4 months preceding the screening visit and have maintained documented undetectable plasma hiv-1 rna levels (\< 50 copies/ml) and must have documentation of genotype/phenotype prior to current regimen which shows no darunavir associated resistance mutation. * currently receiving raltegravir, elvitegravir, or dolutegravir (50 mg once daily, but not twice daily), or have never received integrase inhibitor, or have documentation of genotype/phenotype within 12 months prior to current regimen which must show no evidence of resistance to integrase inhibitors * normal ecg * estimated glomerular filtration rate (egfr) ≥ 50 ml/min according to the cockcroft gault formula for creatinine clearance * hepatic transaminases (ast and alt) ≤ 5 × upper limit of normal (uln) * total bilirubin ≤ 1.5 mg/dl, 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) * a female individual is eligible to enter the study if it is confirmed that she is: * not pregnant or nursing * of non-childbearing potential (i.e., women who have had a hysterectomy, have had both ovaries removed or medically documented ovarian failure, or are postmenopausal women \> 54 years of age with cessation (for ≥ 12 months) of previously occurring menses), or * of childbearing potential and agrees 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 30 days following the last study drug dose. * female individuals 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. * male individuals must 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 30 days following the last study drug dose. * male individuals must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose. key exclusion criteria: * a new aids-defining condition diagnosed within the 30 days prior to screening (except cd4 cell count and/or percentage criteria) * hepatitis b surface antigen (hbsag) 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. * must not have q151m, t69ins, or \> 3 thymidine analogue mutations (tams) present on documented historic genotype report * individuals experiencing decompensated cirrhosis * females who are breastfeeding * positive serum pregnancy test * have an implanted defibrillator or pacemaker * current alcohol or substance use that may interfere with individual's study compliance * a history of malignancy within the past 5 years or ongoing malignancy other than cutaneous kaposi's sarcoma (ks), 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 day 1 visit * any other clinical condition or prior therapy that would make the individual unsuitable for the study or unable to comply with dosing requirements * participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial * individuals receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with elvitegravir, cobicistat, emtricitabine, taf, or drv; or individuals with any known allergies to the study drugs. note: other protocol defined inclusion/exclusion criteria may apply.

Keywords: hiv-1 hiv treatment-experienced