Comparing Standard-Dose Versus Adjusted-Dose Lopinavir/Ritonavir Therapy in HIV-Infected Persons With Drug Resistance
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to see if adjusting the dose of lopinavir/ritonavir (LPV/r) has
      a better effect on lowering HIV viral load (the amount of HIV in the blood) compared to
      taking the standard FDA-approved LPV/r dose. This study will also compare the safety and
      tolerability of these two types of dosing.
    

Detailed description: 
      Antiretroviral drugs may fail to suppress HIV unless there are adequate amounts of those
      drugs in the blood. By monitoring the amounts of drugs in the blood and adjusting doses to
      achieve optimal drug concentrations, response to antiretroviral drugs may improve, especially
      in patients who have failed previous regimens. This study is designed to evaluate drug
      monitoring and dose adjustment of protease inhibitors (PIs) in heavily treatment-experienced
      patients.

      Patients will be randomized to receive either a standard dose of LPV/r (Arm A) or a
      concentration-adjusted dose of LPV/r (Arm B). Concentration-adjusted dosing means that the
      dose of ritonavir or lopinavir may be increased based on the amount of lopinavir measured in
      the blood and the results of a drug resistance test. All patients start the study taking
      LPV/r, tenofovir disoproxil fumarate (TDF), 0 to 2 additional nucleoside reverse
      transcriptase inhibitors (NRTIs), and saquinavir (SQV) or amprenavir (APV). Only LPV/r, TDF,
      and SQV will be provided by the study. Other medications taken as part of the antiretroviral
      regimen must be obtained outside the study.

      Patients in Arm A will take the usual approved dose of LPV/r for the first 24 weeks. At Week
      24, patients with high viral loads will come to the clinic for a 12-hour LPV blood level
      measurement to see if the level of LPV needs to be increased. If it does, an additional
      capsule of ritonavir will be added to the regimen to boost the level of LPV.

      Patients in Arm B will have a series of blood draws over a 12-hour period in the clinic,
      around 14 days after starting the study, to find out if their LPV level needs to be
      increased. If the LPV level needs to be raised, an additional capsule of ritonavir will be
      added to the regimen to boost the level of LPV. Patients who had their ritonavir dose
      adjusted will return to have another 12-hour blood draw around Week 5. If the LPV level still
      needs to be changed, an additional capsule of LPV/r will be added to the regimen. A third
      12-hour blood draw will be performed around Week 8 if a second dose adjustment was necessary.

      During the study, patients will visit the clinic weekly through Week 6, again at Week 8, then
      every 4 weeks thereafter through Week 32. Patients will have blood drawn at certain visits to
      test for LPV level, viral load, CD4 count, fasting lipids and glucose, and drug resistance.
    

Intervention name(s): Lopinavir/ritonavir; Ritonavir; Saquinavir; Tenofovir disoproxil fumarate; Amprenavir
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Ritonavir; Lopinavir; Saquinavir; Amprenavir; Tenofovir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Dose-Relationship, Drug; HIV Protease Inhibitors; Salvage Therapy; Viral Load; RNA, Viral; Drug Therapy, Combination