HIV, HIV Infections, Osteopenia, Osteoporosis
Conditions
Keywords
HIV+, Raltegravir, Tenofovir, osteopenia, osteoporosis, bone markers, treatment experienced
Brief summary
The purpose of this study is to determine if low bone mineral density (a measurement of how thick and strong bones are) improves in adults with HIV infection who switch their HIV medication tenofovir to another HIV medication raltegravir. Hypothesis:That Bone Mineral Density (BMD) will improve in osteopenic or osteoporotic patients switching from ART including tenofovir disoproxil fumarate (TDF) and a ritonavir-boosted protease inhibitor (r/PI) to ART including RAL+r/PI.
Interventions
DRUGRaltegravir
Raltegravir tablet 400mg is taken orally, twice daily with or without food for 48 weeks.
Sponsors
Merck Sharp & Dohme LLC
Holdsworth House Medical Practice
The Alfred
St Vincent's Hospital, Sydney
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
1. provision of written, informed consent 2. HIV-infected adults at least 18 years of age 3. receiving stable ART including TDF and a r/PI for the previous 6 months 4. no prior PI genotypic resistance or known replication of HIV in patients receiving a PI 5. plasma HIV RNA \< 50 copies/ml for at least the previous 3 months 6. spine or neck of femur t-score ≤ -1.0 (i.e. WHO-defined osteopenia) measured by dual energy x-ray absorptiometry (DEXA)
Exclusion criteria
7. participation in any other clinical trial (unless approved by the study PI) 8. use of TDF for previously active chronic hepatitis B infection 9. receiving or requiring therapy for low BMD (including prior fragility fracture) 10. using oral corticosteroids or inhaled fluticasone 11. virological failure on, or intolerance to, RAL 12. contra-indication to RAL therapy (see appendix 2) 13. breast-feeding 14. pregnancy 15. secondary, endocrinological cause of low BMD:25-hydroxy vitamin D deficiency, hypogonadism: a)symptomatic b)asymptomatic defined by total testosterone \> 25% below lower limit of reference range and/or luteinizing hormone \> 2 x upper limit of normal (ULN),untreated hypothyroidism or hyperparathyroidism according to local reference ranges
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Bone Mineral Density (BMD) of Lumbar Spine and Hips | from Baseline to Weeks 48 and 96 | Percent Change in Bone Mineral Density of Lumbar Spine and Hips from Baseline to Weeks 48 and 96 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV Viral Load <50 Copies/mL | from Baseline to Week 96 | Plasma HIV viral load remained \<50 copies/mL |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Raltegravir Raltegravir: Raltegravir tablet 400mg is taken orally, twice daily with or without food for 48 weeks. | 37 |
| Total | 37 |
Baseline characteristics
| Characteristic | Raltegravir |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants |
| Age, Continuous | 50 years |
| Region of Enrollment Australia | 37 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 37 |
| serious Total, serious adverse events | 5 / 37 |
Outcome results
Primary
Percent Change in Bone Mineral Density (BMD) of Lumbar Spine and Hips
Percent Change in Bone Mineral Density of Lumbar Spine and Hips from Baseline to Weeks 48 and 96
Time frame: from Baseline to Weeks 48 and 96
Population: Week 48 data were available for 37 completed participants and Week 96 data were available for 32 completed participants. Fifteen of the enrolled 52 participants were screen failures.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Raltegravir | Percent Change in Bone Mineral Density (BMD) of Lumbar Spine and Hips | Spine BMD, week 48 (n=37) | 2.7 percent change |
| Raltegravir | Percent Change in Bone Mineral Density (BMD) of Lumbar Spine and Hips | Spine BMD, week 96 (n=32) | 3.0 percent change |
| Raltegravir | Percent Change in Bone Mineral Density (BMD) of Lumbar Spine and Hips | Total hip BMD week 48 (n=37) | 2.3 percent change |
| Raltegravir | Percent Change in Bone Mineral Density (BMD) of Lumbar Spine and Hips | Total hip BMD week 96 (n=32) | 1.9 percent change |
p-value: <0.0001t-test, 2 sided
Secondary
Percentage of Participants With HIV Viral Load <50 Copies/mL
Plasma HIV viral load remained \<50 copies/mL
Time frame: from Baseline to Week 96
Population: Week 96 data were available for 32 completed participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir | Percentage of Participants With HIV Viral Load <50 Copies/mL | 90.6 percentage of participants |