Same-Day Treatment With Genvoya vs. EFV/TDF/3TC

An Open-Label, Randomized Comparison of Elvitegravir-Cobicistat-Tenofovir Alafenamide-Emtricitabine Versus Efavirenz-Tenofovir Disoproxil Fumarate-Lamivudine in Patients Starting Antiretroviral Therapy on the Day of HIV Diagnosis

Randomized, open-label study comparing Elvitegravir-Cobicistat-Tenofovir Alafenamide-Emtricitabine (Genvoya) vs. Efavirenz-Tenofovir Disoproxil Fumarate-Lamivudine (EFV-TDF-3TC) in patients starting ART on the day of HIV diagnosis.

Study Overview

• Status: Withdrawn
• Conditions: HIV/AIDS
• Intervention / Treatment: Drug: Elvitegravir, Cobicistat, TAF, FTC; Drug: Efavirenz, TDF, and 3TC

Detailed Description

Patients with WHO Stage 1 or 2 disease at HIV diagnosis will be randomized in a 1:1 ratio to either the Genvoya group or the EFV-TDF-3TC group. ART will be initiated on the day of HIV diagnosis. Participants who are found to have a contraindication to their assigned treatment regimen will change ART, and be classified as a failure for their assigned treatment arm. Participants in the EFV-TDF-3TC group with CrCl of 30-50 mL/minute, or with baseline mutations that significantly reduce the susceptibility of EFV will switch to Genvoya. Participants in the Genvoya group who are diagnosed with TB after enrollment will be switched to an ART regimen that can be administered with rifampin. If the study physician determines that a treatment change is indicated due to intolerability or side effects, the relevant clinical data will be presented to a safety committee that is blinded to group assignment. The ART regimen will be changed if the safety committee determines that it is indicated, and the participant will be considered a failure to their assigned treatment group. Patients will be followed for 48 weeks.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documentation of positive HIV status (test conducted at GHESKIO);
• At least 18 years of age;
• Unaware of HIV diagnosis prior to date of enrollment, and ART-naïve;
• Ability and willingness to give written informed consent;
• Ready to initiate same-day ART, according to two criteria: (1) HIV medication readiness questionnaire; and (2) social worker assessment;
• WHO Stage 1 or 2 disease, as defined by the following conditions: asymptomatic; persistent generalized lymphadenopathy; unexplained weight loss (under 10%); recurrent upper respiratory tract infections; herpes zoster; angular chelitis; recurrent oral ulcerations; papular pruritic eruptions; seborrheic dermatitis; or fungal nail infections.
• Female participants may be enrolled if they are either: (1) post-menopausal; (2) physically incapable of becoming pregnant due to tubal ligation, hysterectomy, or bilateral oophorectomy; or (3) are of childbearing potential, and agree to use one of the following methods to avoid pregnancy throughout the duration of the study:

Complete abstinence from intercourse; Double barrier method, such as male condom/spermicide, male condom/diaphragm, or diaphragm/spermicide; Hormonal contraception plus a barrier method; Intrauterine device (IUD); Male partner sterilization (if participant has only one sexual partner);

Exclusion Criteria:

• Pregnancy or breastfeeding at the screening visit;
• Active drug, alcohol use, or mental condition that would interfere with the ability to adhere to study requirements, in the opinion of the study physician;
• World Health Organization Stage 3 or 4 disease, as defined by the following conditions: unexplained severe weight loss (over 10% of presumed or measured body weight); unexplained chronic diarrhea for longer than 1 month; unexplained persistent fever (intermittent or constant for longer than 1 month); persistent oral candidiasis; oral hairy leukoplakia; pulmonary tuberculosis; severe bacterial infections (e.g. pneumonia, empyema, meningitis, pyomyositis, bone or joint infection, bacteremia, severe pelvic inflammatory disease); or acute necrotizing ulcerative stomatitis, gingivitis or periodontitis.
• Clinical evidence of cirrhosis (ascites or encephalopathy);
• Anticipated need for hepatitis C therapy during the study period;
• Baseline CrCl <30 mL/minute by the Cockcroft-Gault equation (late exclusion, as creatinine results will not be available at the time of enrollment);
• Either the K65R mutation or more than 3 thymidine analogue mutations on baseline resistance testing (late exclusions, after baseline resistance results are available).
• Planning to transfer care to another clinic during the study period;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Elvitegravir-Cobicistat-TAF-FTC; Elvitegravir 150mg po QD Cobicistat 150 mg po QD TAF 10 mg po QD FTC 200 mg QD	Drug: Elvitegravir, Cobicistat, TAF, FTC; Started on day of HIV diagnosis
ACTIVE_COMPARATOR: EFV-TDF-3TC; EFV 600 mg po QD TDF 300 mg po QD 3TC 300 mg po QD	Drug: Efavirenz, TDF, and 3TC; Started on day of HIV diagnosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
48-week viral suppression	To compare the proportion of participants who are retained in care with a plasma HIV-1 RNA level <200 copies/ml	48 weeks after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-week viral suppression	Proportion of participants who are retained in care with a plasma HIV-1 RNA level <200 copies/ml	12 weeks after enrollment
Baseline resistance to ART medications	Genotypic resistance to EFV and/or nucleoside reverse transcriptase inhibitors	Baseline
Change in CD4 count	Median change in CD4 count over the study period (baseline to 48 weeks)	48 weeks after enrollment
Virologic failure	Proportion of patients meeting the WHO definition for ART treatment failure over the study period	48 weeks after enrollment
Adverse events	Proportion of participants with a new Division of AIDS Grade 3 or 4 adverse event or laboratory abnormality that is at least a one-grade increase from baseline	48 weeks after HIV testing
Neurologic or psychiatric adverse event	Proportion of participants with a new Division of AIDS Grade 1 to 4 neurologic or psychiatric disorder that is at least a one-grade increase from baseline	48 weeks
Sleep Quality	Mean scores on the Pittsburgh Sleep Quality Index	4, 12, 24, and 48 weeks after enrollment
Depression	Mean scores on the Patient Health Questionnaires (PHQ-9) Questionnaire	4, 12, 24, and 48 weeks after enrollment
Change in ART drugs	Proportion of participants who discontinue any drug in the original ART regimen	48 weeks after HIV testing after enrollment

Collaborators and Investigators

• Sponsor: Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic
• Collaborators: Gilead Sciences; Brigham and Women's Hospital; Weill Medical College of Cornell University; Analysis Group, Inc.
• Investigators: Principal Investigator: Jean W Pape, MD, Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2018
• Primary Completion (ANTICIPATED): May 1, 2020
• Study Completion (ANTICIPATED): July 1, 2020

Study Registration Dates

• First Submitted: December 24, 2017
• First Submitted That Met QC Criteria: January 12, 2018
• First Posted (ACTUAL): January 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 18, 2020
• Last Update Submitted That Met QC Criteria: March 16, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Efavirenz; HIV/AIDS; Genvoya; Same-Day ART
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Integrase Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Cobicistat; Efavirenz; Elvitegravir
• Other Study ID Numbers: IN-US-292-4500

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes