Clinical trial NCT02180438: An Open Label Trial of Stribild for Antiretroviral (ARV)-naïve HIV-2 Infected Adults in Dakar, Senegal
Official title: An Open Label Trial of STRIBILD™ (Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate) for ARV-naïve HIV-2 Infected Adults in Dakar, Senegal
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV-2 Infection
Keywords: HIV-2
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Clinique des Maladies Infectieuses Ibrahima DIOP Mar/CRCF, Centre Hospitalier Universitaire de Fann
name: Gilead Sciences
First posted: 2014-07-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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)

Primary outcomes:
measure: Death
timeFrame: 48 weeks
measure: New WHO Stage 3 or 4 Event
timeFrame: 48 weeks
measure: Virologic Failure, FDA Snapshot (HIV-2 Plasma Viral Load >50 and >400 Copies/ml)
timeFrame: 48 weeks
Secondary outcomes:
measure: Grade 3 or 4 Adverse Events
timeFrame: 48 weeks
measure: CD4 T-cell Count at 48 Weeks < Baseline
timeFrame: 48 weeks
measure: < 50 CD4 T-cell Increase at 48 Weeks From Baseline
timeFrame: 48 weeks
measure: Switching Off Stribild Prior to 48 Weeks
timeFrame: 48 Weeks
measure: Development of Drug Resistance Mutations to Elvitegravir or Emtricitabine or Tenofovir DF
timeFrame: 48 weeks
Other outcomes:
measure: Interim 24 Weeks Analysis of Death
timeFrame: 24 weeks
measure: Interim Analysis at 24 Weeks of New WHO Stage 3 or 4 Event
timeFrame: 24 weeks
measure: Interim Analysis at 24 Weeks of HIV-2 Virologic Failure
timeFrame: 24 weeks
measure: Interim Analysis at 24 Weeks of Grade 3 and 4 Adverse Events
timeFrame: 24 weeks
Locations:
city: Dakar
country: Senegal
facility: Clinique des Maladies Infectieuses Ibrahima DIOP Mar/CRCF, Centre Hospitalier Universitaire de Fann
Study officials:
affiliation: University of Washington
name: Geoffrey S Gottlieb, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinique des Maladies Infectieuses Ibrahima DIOP Mar/CRCF, Centre Hospitalier Universitaire de Fann
name: Moussa Seydi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.