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

Study Overview
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Brief Summary
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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

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

Conditions
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HIV-2 Infection

Intervention / Treatment
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* Drug: Stribild (Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF) 1 tablet daily X 48 weeks


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-2