HIV-1-infection
Conditions
Keywords
multi-drug resistant
Brief summary
The current study proposal is an open label observational trial for maintenance of virologic suppression, and is designed as a non- inferiority switch trial. The study will involve approximately 30 patients, which includes a PK arm of approximately 10 patients. The study will also include secondary outcomes of quality of life (QOL) and weight changes Hypothesis: Patients with prior NUC or NNRTI resistance (but not to rilpivirine or doravirine) will maintain their virologic suppression after a drug regimen switch from rilpivirine/emtricitabine/tenofovir alafenamide in combination with dolutegravir, to bictegravir/emtricitabine/tenofovir alafenamide in combination with doravirine. The switch therapy will avoid food interactions, and will be well tolerated by subjects.
Interventions
DRUGBictegravir/emtricitabine/tenofovir alafenamide + Doravirine switch
Safety and efficacy of switching from rilpivirine/emtricitabine/tenofovir alafenamide in combination with dolutegravir, to bictegravir/emtricitabine/tenofovir alafenamide in combination with doravirine in male, 45+ year old subjects. The study will also include secondary outcomes of quality of life (QOL) and weight changes.
Sponsors
Gilead Sciences
Quest Clinical Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV positive Males, age 45 or older * Any genotypic or phenotypic resistance except k65R, 69 insertion, integrase resistance, or resistance to rilpivarine or doravirine. * Receiving combination antiretroviral regimen of rilpivirine/emtricitabine/tenofovir alafenamide in combination with dolutegravir \> 12 months and with viral load \<50 copies/ mL on at least one occasion within the six months prior to switch. * Suppressed viral load as defined by one plasma HIV RNA level \< 50 copies/mL within previous 6 months. * Capable of providing informed consent
Exclusion criteria
* Any current or prior integrase inhibitor resistance * Nucleoside reverse transcriptase (NRTI) mutation 69 insertion or k65R mutation * Documented second generation non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (rilpivirine or doravirine)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Viral Suppression | 48 Weeks | Percentage of patients with viral HIV load (VL) \<50 and \<200 copies/mL at 48 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Mass Index | Week 48 | Assess changes in BMI due to treatment switch |
| Work Productivity and Activity | Week 48 | Improvement in work productivity and activity as measured by Work Productivity and Activity Impairment Questionnaire (WPAI). The range of the scale is 0-10, where 0 means it did not have an affect and 10 means it did have an affect. |
| Tolerability of Study Drug | Week 48 | Tolerability of study drugs will be assessed by summarizing the number of AE/SAEs occurring during the study |
| Adverse Events Assessment | Day 28, Weeks 12, 24, 36, & 48 | Assess AE's of any grade and relationship to the drug combination occurring in at least 5% of participants or more. |
| Wellbeing Improvement | Week 48 | Improvement in well-being and sleep inventory as measured by The Pittsburgh Sleep Quality Index (PSQI). Minimum score is 0 and maximum score is 21. A higher score indicates worse quality sleep. |
| PK Assessment | Week 4 (+/- 14 days) with time points at predose (-0.5 hr), 0.5, 1, 2, 4, 6, 8, 12, and 24 hours | Subject plasma concentration-time data of bictegravir and doravirine will be analyzed using non-compartmental model (WinNonlin®) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Biktarvy + Doravirine Switch bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg tablets + doravirine 100mg tablets taken orally once per day
Bictegravir/emtricitabine/tenofovir alafenamide + Doravirine switch: Safety and efficacy of switching from rilpivirine/emtricitabine/tenofovir alafenamide in combination with dolutegravir, to bictegravir/emtricitabine/tenofovir alafenamide in combination with doravirine in male, 45+ year old subjects. The study will also include secondary outcomes of quality of life (QOL) and weight changes. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Biktarvy + Doravirine Switch |
|---|---|
| Age, Continuous | 65 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 19 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 11 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Viral Suppression
Percentage of patients with viral HIV load (VL) \<50 and \<200 copies/mL at 48 weeks
Time frame: 48 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Biktarvy + Doravirine Switch | Viral Suppression | 100 percentage of participants |
Secondary
Adverse Events Assessment
Assess AE's of any grade and relationship to the drug combination occurring in at least 5% of participants or more.
Time frame: Day 28, Weeks 12, 24, 36, & 48
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Biktarvy + Doravirine Switch | Adverse Events Assessment | Mild Adverse Events | 14 Number of AEs |
| Biktarvy + Doravirine Switch | Adverse Events Assessment | Moderate Adverse Events | 1 Number of AEs |
| Biktarvy + Doravirine Switch | Adverse Events Assessment | Severe Adverse Events | 1 Number of AEs |
Secondary
Change in Body Mass Index
Assess changes in BMI due to treatment switch
Time frame: Week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Biktarvy + Doravirine Switch | Change in Body Mass Index | -0.2 kg/m2 | Standard Deviation 0.85 |
Secondary
PK Assessment
Subject plasma concentration-time data of bictegravir and doravirine will be analyzed using non-compartmental model (WinNonlin®)
Time frame: Week 4 (+/- 14 days) with time points at predose (-0.5 hr), 0.5, 1, 2, 4, 6, 8, 12, and 24 hours
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Biktarvy + Doravirine Switch | PK Assessment | Plasma BIC Cmax | 8.55 ug/ml | Geometric Coefficient of Variation 33 |
| Biktarvy + Doravirine Switch | PK Assessment | Plasma DOR Cmax | 1.2 ug/ml | Geometric Coefficient of Variation 34 |
Secondary
Tolerability of Study Drug
Tolerability of study drugs will be assessed by summarizing the number of AE/SAEs occurring during the study
Time frame: Week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Biktarvy + Doravirine Switch | Tolerability of Study Drug | 16 Adverse Events |
Secondary
Wellbeing Improvement
Improvement in well-being and sleep inventory as measured by The Pittsburgh Sleep Quality Index (PSQI). Minimum score is 0 and maximum score is 21. A higher score indicates worse quality sleep.
Time frame: Week 48
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Biktarvy + Doravirine Switch | Wellbeing Improvement | 7 score on a scale |
Secondary
Work Productivity and Activity
Improvement in work productivity and activity as measured by Work Productivity and Activity Impairment Questionnaire (WPAI). The range of the scale is 0-10, where 0 means it did not have an affect and 10 means it did have an affect.
Time frame: Week 48
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Biktarvy + Doravirine Switch | Work Productivity and Activity | Hours of Work Missed | 0 score on a scale |
| Biktarvy + Doravirine Switch | Work Productivity and Activity | Health Problem Affecting Productivity | 0 score on a scale |
| Biktarvy + Doravirine Switch | Work Productivity and Activity | Health Problems Affect on Daily Activities | 0 score on a scale |