An Open Label Trial of Stribild for Antiretroviral (ARV)-naïve HIV-2 Infected Adults in Dakar, Senegal (Stribild HIV-2)

An Open Label Trial of STRIBILD™ (Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate) for ARV-naïve HIV-2 Infected Adults in Dakar, Senegal

There is a critical need for safe and effective antiretroviral treatment (ART) regimens for HIV-2 infection. This is especially true in West Africa, where the vast majority of the 1-2 million individuals infected with HIV-2 live and were access to effective ART for HIV-2 is limited. HIV-2 is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors (NNRTI) and the fusion inhibitor enfuvirtide (T-20) and mutations conferring broad resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) are frequently observed in HIV-2 from patients receiving ART. Although antiretroviral protease inhibitors (PI) can be used effectively to treat HIV- 2, HIV-1 and HIV-2 also exhibit important differences in their susceptibilities with studies indicating that saquinavir (SQV), lopinavir (LPV), and darunavir (DRV) are the only potent PI's against HIV-2 replication and cross-resistance is frequent. Although an increasing body of evidence supports the potential utility of integrase inhibitors (INI) against HIV-2, there have been no clinical trials to assess their effectiveness and they are not routinely available in resource-limited settings. These limitations present major challenges to HIV-2 treatment, particularly in the areas in which it is most prevalent. This study is the 1st use of STRIBILD (elvitegravir (EVG), cobicistat (COBI), emtricitabine (FTC), tenofovir disoproxil fumarate (TDF)), an INI-based single tablet regimen, in HIV-2 infected adults in West Africa. The investigators hypothesize STRIBILD will be safe and effective as ART for HIV-2 infection. The Specific Aims of this study are: AIM 1: A pilot, open label, 48 week trial of STRIBILD (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) in 30 ARV-naïve HIV-2 Infected Adults in Dakar, Senegal. AIM 2: Determination of genotypic and phenotypic HIV-2 antiretroviral resistance in individuals with virologic failure (HIV-2 plasma RNA >250 copies/ml) participating in the 48 week trial of STRIBILD

Study Overview

• Status: Completed
• Conditions: HIV-2 Infection
• Intervention / Treatment: Drug: Stribild (Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF) 1 tablet daily X 48 weeks

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Senegal
  • Dakar, Senegal
    • Clinique des Maladies Infectieuses Ibrahima DIOP Mar/CRCF, Centre Hospitalier Universitaire de Fann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent
• Age > 18 years old
• HIV-2 Infection (confirmed by DetermineTM & Immunocomb II)
• ARV-naïve
• CD4 count < 750 cells/mm3 and/or WHO Stage 3 or 4 disease
• Anticipate residing in Dakar area for duration of study

Exclusion Criteria:

• Pregnancy or Breast feeding
• HIV-1 or HIV-1/HIV-2 dual infection
• Known allergy or contraindication to Elvitegravir, Cobicistat, Emtricitabine, or Tenofovir DF
• Active Tuberculosis (STRIBILD contraindicated with rifampin)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open label prospective single arm study of Stribild	Drug: Stribild (Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF) 1 tablet daily X 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	Number of Participants Experiencing Death within the study period	48 weeks
New WHO Stage 3 or 4 Event	New AIDS defining event per WHO criteria	48 weeks
Virologic Failure, FDA Snapshot (HIV-2 Plasma Viral Load >50 and >400 Copies/ml)		48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade 3 or 4 Adverse Events	Adverse event per NIH/DAIDS criteria	48 weeks
CD4 T-cell Count at 48 Weeks < Baseline		48 weeks
< 50 CD4 T-cell Increase at 48 Weeks From Baseline		48 weeks
Switching Off Stribild Prior to 48 Weeks		48 Weeks
Development of Drug Resistance Mutations to Elvitegravir or Emtricitabine or Tenofovir DF		48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interim 24 Weeks Analysis of Death		24 weeks
Interim Analysis at 24 Weeks of New WHO Stage 3 or 4 Event		24 weeks
Interim Analysis at 24 Weeks of HIV-2 Virologic Failure	Virologic failure, FDA Snapshot (HIV-2 plasma viral load >50 and >400 copies/ml)	24 weeks
Interim Analysis at 24 Weeks of Grade 3 and 4 Adverse Events		24 weeks

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Gilead Sciences; Clinique des Maladies Infectieuses Ibrahima DIOP Mar/CRCF, Centre Hospitalier Universitaire de Fann
• Investigators: Principal Investigator: Moussa Seydi, MD, Clinique des Maladies Infectieuses Ibrahima DIOP Mar/CRCF, Centre Hospitalier Universitaire de Fann

Publications and helpful links

General Publications

• Ba S, Raugi DN, Smith RA, Sall F, Faye K, Hawes SE, Sow PS, Seydi M, Gottlieb GS; University of Washington-Dakar HIV-2 Study Group. A Trial of a Single-tablet Regimen of Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate for the Initial Treatment of Human Immunodeficiency Virus Type 2 Infection in a Resource-limited Setting: 48-Week Results From Senegal, West Africa. Clin Infect Dis. 2018 Oct 30;67(10):1588-1594. doi: 10.1093/cid/ciy324.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: May 29, 2014
• First Submitted That Met QC Criteria: July 1, 2014
• First Posted (Estimate): July 2, 2014

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: June 30, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: HIV-2
• Additional Relevant MeSH Terms: 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; Integrase Inhibitors; Tenofovir; Emtricitabine; Cobicistat; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Elvitegravir
• Other Study ID Numbers: STUDY00000757

Drug and device information, study documents

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