Study of the Effect of Atorvastatin for Reducing Aging-related Complication in HIV-infected Patients Older Than 45 Years Receiving a Protease Inhibitor-based Regimen Versus a Raltegravir-based Regimen
Condition: Aging-related Inflammation in HIV-infected Patients
MeSH terms: Inflammation
Intervention: Raltegravir; PI-based regimen; Atorvastatin
Intervention description: Switching the PI by raltegravir 400mg every 12 hours, plus Kivexa or Truvada, for 24 weeks.; Continue with the same PI-based regimen, plus Kivexa or Truvada, for 24 weeks.; Atorvastatin, 20mg/day, will be added after 24 weeks of study for 48 weeks
Intervention MeSH terms: Raltegravir Potassium; Atorvastatin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 60 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Raltegravir; protease inhibitors; darunavir; inflammation; statins; comorbidities

Summary:

      Physicians in charge of HIV-infected patients are increasingly being faced to previously
      unrecognized comorbid conditions such as atherosclerosis and cardiovascular events, loss of
      renal function, osteopenia/osteoporosis and bone fractures or non-AIDS-defining cancers
      (1-4). The incidence of these conditions seems to be higher than in the general population
      but there are controversial data about if these diseases appear at a younger age in
      HIV-infected patients.

      The investigators propose a strategy for treatment of elderly HIV-infected patients with a
      double impact on systemic inflammation and age-related co-morbidities by switching the
      protease inhibitors by raltegravir, a integrase inhibitor with a neutral effect on lipid and
      bone metabolism, and adding an statin because of their anti-inflammatory effect. For safety
      reasons, only patients with maintained viral suppression (documented indetectable viral load
      for 1 year or more), and no history of virological failure to integrase inhibitors or
      suspected or documented resistance mutations to the integrase or retrotranscriptase will be
      candidates for the study.

      Interleukin -6 and D-dimer are biomarkers that most strongly predict mortality in treated HIV
      infection and sCD14, sCD163 are soluble markers of monocyte activation that reflect a key
      source of inflammation and coagulation in HIV infection and predict mortality (26,27). For
      that reasons, these markers were chosen to determine changes on them after the introduction
      of the statin and the change of antiretrovirals
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient having a diagnosis of HIV-1 infection.

          -  Age 45 years old.

          -  Current highly active antiretroviral therapy including Truvada or Kivexa plus a
             ritonavir boosted PI started at least 3 months before.

          -  Maintained undetectable plasma HIV-1 RNA (VL < 50 copies/mL) for at least 12 months.

          -  Voluntary written informed consent.

        Exclusion Criteria:

          -  History of virological failure to integrase inhibitors.

          -  Suspected or documented resistance mutations to the integrase, as well as NRTI-related
             mutations that may impact nucleoside activity in current regimen.

          -  Systemic concurrent process such as coinfection with hepatitis C or B, acute systemic
             infection within the last 4 months, neoplasm, chronic inflammatory process, etc.

          -  Treatment with other drugs with anti-inflammatory, anticoagulant or antiplatelet
             effect (for instance corticosteroids, aspirin, etc…)

          -  Therapy with statins within the last 6 months.