HIV
Conditions
Keywords
HIV, Pharmatokinetic, 60 years old, Raltegravir
Brief summary
This is a phase IV, open label, prospective, one phase pharmacokinetic and observational study. Twenty HIV-1 infected subjects will be recruited, subjects will switch antiretroviral therapy to: * tenofovir/emtricitabine 245/200 mg daily (Truvada™) plus * raltegravir 400 mg twice daily On day 28, all subjects will attend for an intensive 24 hour pharmacokinetic visit.
Detailed description
This is a phase IV, open label, prospective, one phase pharmacokinetic and observational study. Twenty HIV-1 infected subjects will be recruited. Eligible subjects will currently be receiving stable antiretroviral therapy with undetectable plasma HIV RNA and have no evidence of previous HIV- resistance mutations on genotypic resistance testing. At baseline, subjects will switch antiretroviral therapy to: * tenofovir/emtricitabine 245/200 mg daily (Truvada™) plus * raltegravir 400 mg twice daily On day 28, all subjects will attend for an intensive 24 hour pharmacokinetic visit. Follow up over 6 months, subjects will attend on days 14, 90 and 180 for follow up visits that will include standard safety parameters. Assessment of cardiac biomarkers at baseline and on days 90 and 180 and assessment of neurocognitive function at screening, baseline and on day 180 will also be undertaken. Following completion of this study, subjects will recommence their usual antiretroviral treatment regimen and attend for a study follow up visit.
Interventions
DRUGRaltegravir
400 mg twice daily
DRUGTenofovir
245 mg once daily
DRUGEmtricitabine
200mg once daily
Sponsors
Imperial College London
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
HIV affected over 60 years old
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. HIV-1 infected males or females 2. 60 years of age or greater\* 3. signed informed consent 4. willing to switch therapy as per study protocol 5. no previous exposure to raltegravir or HIV-1 integrase inhibitors 6. plasma HIV RNA \< 50 copies/mL at screening and on at least one other occasion over the last 3 months 7. currently receiving a stable antiretroviral regimen with no antiretroviral drug switches for at least 3 months 8. no previous clinically-significant resistance documented on HIV-1 genotypic resistance 9. subjects in good health upon medical history, physical exam, and laboratory testing 10. BMI above or equal to 18 and below 32 11. Male subjects who are heterosexually active must use two forms of barrier contraception (e.g., condom with spermicide) during heterosexual intercourse, from screening through completion of the study. 12. Have local screening laboratory results (haematology and chemistry that fall within the normal range of the central laboratory's reference ranges unless the results have been determined by the Investigator to have no clinical significance \* 50% of total enrolled cohort will be 65 years of age or over. Subsequent to 10 subjects aged between 60 and 64 recruited, only subjects aged 65 or over will be eligible.
Exclusion criteria
1. current alcohol abuse or drug dependence 2. positive urine drug of abuse screening 3. active opportunistic infection or significant co-morbidities 4. current disallowed concomitant medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug Levels in Blood | Day 28 | rategravir concentration |
| Changes in Haematology, Biochemistry and Virology Tests | 6 months | full blood count, electrolytes and blood lipids will be measured at all visits to assess for changes through out the study. HIV viral load will also be measured to assess the efficacy of the medication at controlling the virus |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular Disease Markers | 6 months | • To investigate cardiovascular disease markers before and after a switch in antiretroviral therapy to raltegravir. |
| Cerebral Function; Changes in Global Cognitive Z-score | 6 months | Cerebral function via cognitive testing before and after a switch in antiretroviral therapy to raltegravir. Mean Scores from the eight tasks (NPZ-8) assessed were used to derive a global composite measure of neurocognitive function. The result shows the change before and after switch, an increase in z-score represents an improvement in cognitive function assessed by CogState battery, required approximately 10-15 min for completion. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Truvada Plus Raltegravir Single arm study
Raltegravir: 400 mg twice daily | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | Truvada Plus Raltegravir |
|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 3.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 16 Participants |
| Region of Enrollment United Kingdom | 19 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 0 / 19 |
| serious Total, serious adverse events | 0 / 19 |
Outcome results
Primary
Changes in Haematology, Biochemistry and Virology Tests
full blood count, electrolytes and blood lipids will be measured at all visits to assess for changes through out the study. HIV viral load will also be measured to assess the efficacy of the medication at controlling the virus
Time frame: 6 months
Population: No data collected
Primary
Drug Levels in Blood
rategravir concentration
Time frame: Day 28
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Truvada Plus Raltegravir | Drug Levels in Blood | 1732 ng/ml |
Secondary
Cardiovascular Disease Markers
• To investigate cardiovascular disease markers before and after a switch in antiretroviral therapy to raltegravir.
Time frame: 6 months
Population: No data collected
Secondary
Cerebral Function; Changes in Global Cognitive Z-score
Cerebral function via cognitive testing before and after a switch in antiretroviral therapy to raltegravir. Mean Scores from the eight tasks (NPZ-8) assessed were used to derive a global composite measure of neurocognitive function. The result shows the change before and after switch, an increase in z-score represents an improvement in cognitive function assessed by CogState battery, required approximately 10-15 min for completion.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Truvada Plus Raltegravir | Cerebral Function; Changes in Global Cognitive Z-score | 0.91 score on a scale | Standard Deviation 1.3 |
Comparison: Compare baseline to 24 weeksp-value: 0.018Regression, Logistic