Multicentre Study To Assess Changes In Bone Mineral Density Of The Switch From Protease Inhibitors To Dolutegravir In HIV-1-Infected Subjects With Low Bone Mineral Density

• Status: Completed
• Trial end date: 2015-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fundacio Lluita Contra la SIDA; Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
• Treatments: Dolutegravir; HIV Protease Inhibitors; Protease Inhibitors; Ritonavir

Criteria

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.