HIV-1 Infection
Conditions
Keywords
Osteoporosis, Bone mineral density, Dual-energy X-ray absorptiometry, HIV infection, Dolutegravir, Integrase inhibitor
Brief summary
Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals because of an enhanced osteoclast activity, although some controversial data have been also published. A first study suggest an increase of bone mineral density after switching from PI to raltegravir, the first generation integrase inhibitor, but there are no more data about this subject. Based on data that PI decrease bone mineral density by accelerating osteoclast cells and that the discontinuation of this drugs could improve bone mineralization, we propose a randomized prospective multicenter study to assess the impact of switching from PI to dolutegravir on bone mineral density in patients with low bone mineral density receiving a PI-containing regimen. At the same time, the study will help to assess the antiviral efficacy and safety of a PI-sparing regimen including dolutegravir as a simplification strategy in virologically suppressed patients.
Detailed description
The second generation integrase inhibitor dolutegravir has demonstrated good virological and immunological outcomes in antiretroviral-naive subjects, compared with efavirenz, (SPRING 1 study). As well, it is active against HIV strains resistant to first-generation inhibitors raltegravir and elvitegravir in heavily treatment-experienced patients (VIKING study). Additionally, it was safe and well tolerated after two years of use. It is administered once daily with no need for boosting, no food requirements and has a long half-life. The easy posology and its pharmacokinetics, together with the antiviral potency, make this drug a good alternative as a simplification approach. However, no clinical data are available supporting the switch of protease inhibitors or no nucleoside reverse transcriptase inhibitors to dolutegravir in virologically suppressed HIV-treated subjects. Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals because of an enhanced osteoclast activity, although some controversial data have been also published. A first study suggest an increase of bone mineral density after switching from PI to raltegravir, the first generation integrase inhibitor, but there are no more data about this subject. Based on data that PI decrease bone mineral density by accelerating osteoclast cells and that the discontinuation of this drugs could improve bone mineralization, we propose a randomized prospective multicenter study to assess the impact of switching from PI to dolutegravir on bone mineral density in patients with low bone mineral density receiving a PI-containing regimen. At the same time, the study will help to assess the antiviral efficacy and safety of a PI-sparing regimen including dolutegravir as a simplification strategy in virologically suppressed patients.
Interventions
DRUGDolutegravir, 50mg every 24 hours
Dolutegravir, 50mg every 24 hours
DRUGProtease Inhibitor/ritonavir
Protease Inhibitor/ritonavir
Sponsors
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. HIV-infected patients over 18 years. 2. In current antiretroviral therapy with abacavir and lamivudine (Kivexa) plus ritonavir-boosted PI, at least 6 months. 3. Viral suppression (HIV RNA \<50 copies / ml) for at least 12 months. 4. T-score ≤ -1 evaluated by DEXA (done in the last 6 months). 5. Signed informed consent. 6. In potential childbearing women, commitment to use barrier contraceptive method throughout the study.
Exclusion criteria
1. Suspected or documented resistance to integrase inhibitors or reverse transcriptase inhibitors, nucleoside analogues. 2. Osteoporosis / osteopenia secondary (testosterone deficiency, thyroid disease ...), except vitamin D deficiency 3. Treatment with bisphosphonates in the last 6 months. 4. Have used integrase inhibitors 5. Pregnant or breastfeeding. 6. Patients with alanine aminotransferase (ALT)\> 5 times the upper limit of normal (ULN) or ALT ≥ 3 times ULN and bilirubin ≥ 1.5 times ULN (direct bilirubin\> 35%) 7. Patients with severe hepatic dysfunction (Class B or C) according to the Child-Pugh classification 8. Patients infected with hepatitis B virus (HBV) who can not use entecavir or telbivudine. 9. Patients infected with hepatitis C virus (HCV) in which is expected to begin treatment during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Compare changes in Bone Mineral Density (BMO) measured by Dual-energy X-ray absorptiometry | From Baseline to week 48 |
| Compare changes in femur T-score measured by DEXA | From Baseline to week 48 |
| Compare changes in lumbar spine (L1-L4) T-score measured by DEXA | From Baseline to week 48 |
Secondary
| Measure | Time frame |
|---|---|
| Compare changes in total cholesterol | at week 48 relative to baseline values |
| Compare changes in HDL cholesterol | at week 48 relative to baseline values |
| Compare changes in LDL cholesterol | at week 48 relative to baseline values |
| Compare changes in triglyceride levels. | at week 48 relative to baseline values |
| Compare changes in filtrate glomerular rate by MDRD equation | at week 48 relative to baseline values |
| Compare changes in creatinine | at week 48 relative to baseline values |
| HIV-1 viral load | Baseline |
| Compare changes in proteinuria/creatinine ratio | at week 48 relative to baseline values |
| Adverse events related to antiretroviral treatment (Toxicity). | From Baseline to week 48 |
| Patient withdrawal | From Baseline to week 48 |
| Compare changes in osteocalcin | at week 48 relative to baseline values |
| Compare changes in alkaline phosphatase | at week 48 relative to baseline values |
| Compare changes in telopeptide | at week 48 relative to baseline values |
| Compare changes in albumine/creatinine ratio | at week 48 relative to baseline values |
| CD4+/CD8+ T lymphocytes count. | Baseline |
| Genotypic test if virological failure occurs. | From baseline to week 48 |
Countries
Spain
Outcome results
None listed