Anti-HIV Drug Regimens With or Without Protease Inhibitors and Drug Level Monitoring in HIV Infected Adolescents
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to compare the effectiveness of anti-HIV drug regimens with or
      without a protease inhibitor (PI) in HIV infected adolescents. It will also determine if
      monitoring drug levels and adjusting the dose as necessary improves the effectiveness of
      these regimens.
    

Detailed description: 
      HIV infected adolescents may have a significantly higher capacity for immune reconstitution
      following highly active antiretroviral therapy (HAART), compared to adults. Despite this
      advantage, HIV infected adolescents are often reluctant to get proper medical care, follow
      through with doctor appointments, and adhere to medication schedules and regimens necessary
      to keep their infection under control. Lopinavir/ritonavir (LPV/r), a PI, and efavirenz
      (EFV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), both have long half-lives
      that make them ideal drugs for the adolescent population, as they are more forgiving if
      patients miss or sleep through doses. The availability of once-daily dosing of LPV/r will
      reduce pill burden and offers more flexibility in medication scheduling, also helping to
      promote treatment adherence among this age group. This study will examine the effectiveness
      of two HAART regimens, one with the PI LPV/r and two nucleoside reverse transcriptase
      inhibitors (NRTIs), and the other with the NNRTI EFV and two NRTIs. The efficacy of
      therapeutic drug monitoring (TDM) and subsequent dose adjustment will also be assessed with
      both regimens.

      Patients will be enrolled in this study for 96 weeks and will be randomly assigned into one
      of two groups. Group 1 will receive LPV/r and 2 NRTIs. Treatment naive patients in Group 1
      will have the option of receiving either once-daily dosing or twice-daily dosing of LPV/r.
      Treatment experienced patients will receive twice-daily dosing of LPV/r. Patients on
      once-daily dosing of LPV/r who become intolerant to the regimen will be permitted to switch
      to twice-daily dosing. Group 2 will receive EFV and 2 NRTIs. All patients will be
      independently and simultaneously randomly assigned to undergo either TDM with subsequent dose
      adjustment if necessary or no TDM.

      Patient medical history and physical exam will be conducted at screening, entry, Weeks 2, 4,
      8, every 8 weeks until Week 48, and every 12 weeks thereafter. Blood collection will occur at
      all study visits. Self-reported pill counts and MEMS TrackCap readings (on LPV/r and EFV
      bottles) will be noted at most visits. Patients will be asked to complete adherence
      questionnaires at selected study visits.

      Patients enrolled in PACTG 390 (Different Combination Regimens and Treatment-Switching
      Guidelines in HIV Infected Children 18 Years of Age and Younger) are encouraged to coenroll
      simultaneously in this study and in PACTG 219C (Long-Term Effects of HIV Exposure and
      Infection in Children).
    

Intervention name(s): Efavirenz + 2 NRTIs; Lopinavir/Ritonavir + 2 NRTIs; Therapeutic Drug Monitoring
Intervention type(s): Drug; Drug; Procedure
Intervention MeSH terms: Ritonavir; Lopinavir; Efavirenz
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Acute Infection; Treatment Experienced; Treatment Naive