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
Condition: HIV-1 Infection
MeSH terms: Bone Diseases, Metabolic
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Dolutegravir, 50mg every 24 hours; Protease Inhibitor/ritonavir
Intervention type(s): Drug; Drug
Intervention description(s): Dolutegravir, 50mg every 24 hours; Protease Inhibitor/ritonavir
Intervention MeSH terms: Ritonavir; HIV Protease Inhibitors; Dolutegravir; Protease Inhibitors
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Osteoporosis; Bone mineral density; Dual-energy X-ray absorptiometry; HIV infection; Dolutegravir; Integrase inhibitor