A Study on Possible Interactions Between Protease Inhibitors (Anti-HIV Drugs) and Drugs Which Lower the Level of Fat in Your Blood
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to find out whether taking protease inhibitors (anti-HIV drugs)
      together with lipid-lowering drugs (drugs which lower the amount of fat in the blood) has an
      effect on the level of drugs found in the blood compared to when these drugs are taken
      separately. The three protease inhibitors given in this study are ritonavir, saquinavir, and
      nelfinavir. The lipid-lowering drugs given are pravastatin, simvastatin, and atorvastatin.

      Anti-HIV drug therapy using protease inhibitors has become very common treatment for
      HIV-positive patients. Recently, however, serious side effects involving how the body uses
      fat have been reported in people taking protease inhibitors. Examples of these side effects
      are redistribution of body fat and development of diabetes. People taking protease inhibitors
      have been found to have higher levels of fat in their blood than is normal, which can cause
      heart problems. It is hoped that giving lipid-lowering drugs can help prevent serious heart
      problems. First, however, it is important to see what happens when protease inhibitors and
      lipid-lowering drugs are given together.
    

Detailed description: 
      Potent antiretroviral therapy has become the standard of care for persons with HIV infection
      and AIDS. Recently, however, a number of complications have emerged with the widespread use
      of protease inhibitor (PI)-based regimens, including: hyperlipidemia, hypertriglyceridemia,
      diabetes mellitus, and lipodystrophy. Concern over the possibility of premature myocardial
      infarction has led health care providers and patients to consider treating these lipid
      metabolism disorders. Statin compounds have beneficial effects as lipid-lowering agents, and
      thereby reduce the risk of cardiovascular complications. Statin compounds such as
      pravastatin, simvastatin, and atorvastatin are increasingly being prescribed in persons
      taking PI-based potent antiretroviral therapy. It is important to determine whether there are
      significant drug-drug interactions between the statin compounds and PIs.

      Fourteen healthy participants for each cohort of Arm A are stabilized on a fixed regimen of
      pravastatin (Arm A1), simvastatin (Arm A2), or atorvastatin (Arm A3) for 4 days. A baseline
      pharmacokinetic (PK) evaluation is completed on Day 4. Pravastatin (or simvastatin or
      atorvastatin) dosing stops following the Day 4 dose and PK evaluation. On Day 5, a ritonavir
      and saquinavir combination regimen is initiated and continued through Day 18 of the study.
      Pravastatin (or simvastatin or atorvastatin) dosing resumes on Day 15 and continues through
      Day 18. A repeat PK evaluation of pravastatin (or simvastatin or atorvastatin) in the context
      of combination therapy is carried out on Day 18.

      Fourteen healthy participants are assigned to Arm B; these participants begin a 2-week
      regimen of nelfinavir. On Day 14, a baseline PK profile of nelfinavir and its M8 metabolite
      is carried out. Pravastatin is then added to the regimen for Days 15 to 18. On Day 18, a
      repeat PK evaluation of nelfinavir and the M8 metabolite is carried out in the context of
      combination therapy.
    

Intervention name(s): Pravastatin sodium; Simvastatin; Atorvastatin calcium; Ritonavir; Nelfinavir mesylate; Saquinavir
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Ritonavir; Nelfinavir; Saquinavir; Atorvastatin; Simvastatin; Pravastatin; Calcium
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug Interactions; HIV Protease Inhibitors; Ritonavir; HIV Seronegativity; Saquinavir; Nelfinavir; Anticholesteremic Agents