efficacy of tenofovir alafenamide versus placebo added to a failing regimen followed by treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide plus atazanavir in hiv-1 positive, antiretroviral treatment-experienced adults

Conditions: HIV; HIV Infections; Acquired Immunodeficiency Syndrome

Summary: the primary objective of this study is to evaluate the efficacy of tenofovir alafenamide (taf) versus placebo, each administered with the existing, failing antiretroviral (arv) regimen. there are 2 parts to this study: part 1 and part 2. part 1 consists of 2 cohorts, starting with a sentinel cohort, in which participants will be enrolled to receive open-label taf in addition to their current failing arv regimen. this cohort will then be followed by a randomized, double-blind, cohort to compare the addition of taf or placebo in hiv-1 positive adults who are failing their current arv regimen. in part 2, all participants who complete part 1 of the study will discontinue their failing arv regimen and taf or placebo for a 14-day washout period. following the washout period, all participants who received taf in part 1 and have a \> 0.5 log10 decline in hiv-1 rna will receive elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (e/c/f/taf) single-tablet regimen (str) plus atazanavir (atv) once daily for 48 weeks. participants who received taf who have a ≤ 0.5 log10 decline in hiv-1 rna will be discontinued from the study and will not be eligible to continue into part 2 of the study. all participants who received placebo in part 1 will be eligible to participate in part 2 regardless of their viral load change. after completion of part 2, all participants will be eligible to continue to receive e/c/f/taf plus atv in the extension phase until e/c/f/taf becomes commercially available, or until gilead sciences terminates development of e/c/f/taf in the applicable country.


Eligibility criteria:
key inclusion criteria: * ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures * currently taking a failing arv regimen * plasma hiv-1 rna ≥ 500 copies/ml but ≤ 100,000 copies/ml at screening * normal ecg * estimated glomerular filtration rate (egfr) ≥ 50 ml/min according to the cockcroft-gault formula for creatinine clearance * alanine aminotransferase (ast)/aspartate aminotransferase (ast) ≤ 5 × the upper limit of the normal range (uln) * total bilirubin ≤ 1.5 mg/dl, or normal direct bilirubin * adequate hematologic function * serum amylase ≤ 5 × uln * females may enter the study if it is confirmed that she is: * not pregnant or nursing * of non-childbearing potential (ie, have had a hysterectomy, both ovaries removed, 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 study drug dosing * 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 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. * males 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 * hepatitis b surface antigen (hbsag) positive * hepatitis c antibody positive (individuals with positive hepatitis c virus (hcv) antibody and without detectable hcv rna are permitted to enroll) * history of integrase inhibitor use * screening or historical genotype reports shows q151m or t69ins or more than 3 tams. * screening or historical genotype report shows resistance to integrase inhibitors * individuals experiencing decompensated cirrhosis * current alcohol or substance use * 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 part 1, day 1 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 part 1, day 1 * 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 * receiving ongoing therapy with any disallowed medications, including any drugs not to be used with elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide or known allergies to the excipients of e/c/f/taf str note: other protocol defined inclusion/exclusion criteria may apply.

Keywords: hiv-1 hiv treatment-experienced