HIV-2 Infection
Conditions
Keywords
HIV-2
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
Interventions
DRUGStribild (Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF) 1 tablet daily X 48 weeks
Sponsors
Clinique des Maladies Infectieuses Ibrahima DIOP Mar/CRCF, Centre Hospitalier Universitaire de Fann
Gilead Sciences
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Death | 48 weeks | Number of Participants Experiencing Death within the study period |
| Virologic Failure, FDA Snapshot (HIV-2 Plasma Viral Load >50 and >400 Copies/ml) | 48 weeks | — |
| New WHO Stage 3 or 4 Event | 48 weeks | New AIDS defining event per WHO criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| < 50 CD4 T-cell Increase at 48 Weeks From Baseline | 48 weeks | — |
| Grade 3 or 4 Adverse Events | 48 weeks | Adverse event per NIH/DAIDS criteria |
| CD4 T-cell Count at 48 Weeks < 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
| Measure | Time frame | Description |
|---|---|---|
| Interim Analysis at 24 Weeks of New WHO Stage 3 or 4 Event | 24 weeks | — |
| Interim Analysis at 24 Weeks of Grade 3 and 4 Adverse Events | 24 weeks | — |
| Interim 24 Weeks Analysis of Death | 24 weeks | — |
| Interim Analysis at 24 Weeks of HIV-2 Virologic Failure | 24 weeks | Virologic failure, FDA Snapshot (HIV-2 plasma viral load \>50 and \>400 copies/ml) |
Countries
Senegal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Label Prospective Single Arm Study of Stribild Stribild (Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF) 1 tablet daily X 48 weeks | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Open Label Prospective Single Arm Study of Stribild |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants |
| Age, Continuous | 49 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Senegal | 30 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 30 |
| serious Total, serious adverse events | 1 / 30 |
Outcome results
Primary
Death
Number of Participants Experiencing Death within the study period
Time frame: 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Prospective Single Arm Study of Stribild | Death | 0 Participants |
Primary
New WHO Stage 3 or 4 Event
New AIDS defining event per WHO criteria
Time frame: 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Prospective Single Arm Study of Stribild | New WHO Stage 3 or 4 Event | 0 Participants |
Primary
Virologic Failure, FDA Snapshot (HIV-2 Plasma Viral Load >50 and >400 Copies/ml)
Time frame: 48 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open Label Prospective Single Arm Study of Stribild | Virologic Failure, FDA Snapshot (HIV-2 Plasma Viral Load >50 and >400 Copies/ml) | >50 copies/mL | 1 Participants |
| Open Label Prospective Single Arm Study of Stribild | Virologic Failure, FDA Snapshot (HIV-2 Plasma Viral Load >50 and >400 Copies/ml) | >400 copies/mL | 0 Participants |
Secondary
< 50 CD4 T-cell Increase at 48 Weeks From Baseline
Time frame: 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Prospective Single Arm Study of Stribild | < 50 CD4 T-cell Increase at 48 Weeks From Baseline | 2 Participants |
Secondary
CD4 T-cell Count at 48 Weeks < Baseline
Time frame: 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Prospective Single Arm Study of Stribild | CD4 T-cell Count at 48 Weeks < Baseline | 0 Participants |
Secondary
Development of Drug Resistance Mutations to Elvitegravir or Emtricitabine or Tenofovir DF
Time frame: 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Prospective Single Arm Study of Stribild | Development of Drug Resistance Mutations to Elvitegravir or Emtricitabine or Tenofovir DF | 1 Participants |
Secondary
Grade 3 or 4 Adverse Events
Adverse event per NIH/DAIDS criteria
Time frame: 48 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open Label Prospective Single Arm Study of Stribild | Grade 3 or 4 Adverse Events | Lab: Grade 3 or 4 | 7 Participants |
| Open Label Prospective Single Arm Study of Stribild | Grade 3 or 4 Adverse Events | Clinical: Grade 3 or 4 | 1 Participants |
Secondary
Switching Off Stribild Prior to 48 Weeks
Time frame: 48 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Prospective Single Arm Study of Stribild | Switching Off Stribild Prior to 48 Weeks | 0 Participants |
Other Pre-specified
Interim 24 Weeks Analysis of Death
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Prospective Single Arm Study of Stribild | Interim 24 Weeks Analysis of Death | 0 participants |
Other Pre-specified
Interim Analysis at 24 Weeks of Grade 3 and 4 Adverse Events
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Prospective Single Arm Study of Stribild | Interim Analysis at 24 Weeks of Grade 3 and 4 Adverse Events | 0 Participants |
Other Pre-specified
Interim Analysis at 24 Weeks of HIV-2 Virologic Failure
Virologic failure, FDA Snapshot (HIV-2 plasma viral load \>50 and \>400 copies/ml)
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Prospective Single Arm Study of Stribild | Interim Analysis at 24 Weeks of HIV-2 Virologic Failure | 0 Participants |
Other Pre-specified
Interim Analysis at 24 Weeks of New WHO Stage 3 or 4 Event
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Prospective Single Arm Study of Stribild | Interim Analysis at 24 Weeks of New WHO Stage 3 or 4 Event | 0 Participants |