Treatment Options for Protease Inhibitor-exposed Children
Condition: HIV/AIDS; HIV Infections
MeSH terms: HIV Infections
Intervention: Efavirenz (EFV); Lopinavir/ritonavir (LPV/r); Stavudine (D4T); Abacavir (ABC)
Intervention description: Children are assigned to begin a EFV-based antiretroviral based regimen.; Children are assigned to stay on their current LPV/r-based antiretroviral regimen.; Children are assigned to stay on their current antiretroviral regimen which includes D4T.; Children stop taking D4T and switch to ABC.
Intervention MeSH terms: Ritonavir; Lopinavir; Abacavir; Stavudine; Efavirenz
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 300.0
Sex: All
Minimum age: 3 Years
Healthy volunteers: No

Summary:

      The investigators hypothesize that switching to a regimen based on efavirenz will be as
      effective and safe as remaining on a regimen based on Lopinavir/ritonavir for HIV-infected
      children.

      The investigators propose an unblinded randomized clinical trial to evaluate a
      simplification, protease-inhibitor (PI)-sparing treatment strategy among nevirapine
      (NVP)-exposed HIV-infected children treated initially with lopinavir/ritonavir (LPV/r).
      HIV-infected children aged 3-5 years, who have a history of exposure to NVP as part of
      prevention of mother-to-child HIV transmission (PMTCT), initiated LPV/r-based therapy in the
      first 36 months of life or who were enrolled on the control arm of Neverest 2 and who are
      virally suppressed with a viral load < 50 copies/ml will be included. These children will be
      randomized to either substitute efavirenz (EFV) for LPV/r or to continue on their LPV/r-based
      regimen. Eight weeks prior to the primary randomization, eligible children will also be
      randomized to either remain on stavudine (D4T) or switch to abacavir (ABC). Children will be
      followed with regular viral load and other clinical tests for 48 weeks after the primary
      randomization. Children in the experimental arm who have breakthrough viremia (-defined as
      two subsequent viral loads > 1000 copies/ml) on the EFV-based regimen will reinitiate the
      LPV/r regimen. The primary objective is to test whether the durability of viral suppression
      is equivalent when children are switched to EFV-based therapy. The primary study endpoint is
      failure to have HIV RNA < 50 copies/ml and/or confirmed viremia >1000 copies/ml. Secondary
      aims include comparison of immune preservation, toxicities, selection of resistance
      mutations, and adherence across the two arms. Antiretroviral drug concentrations and
      adherence will be investigated as possible explanations for the success and/or failure of
      this simplification regimen. The overall goal of the study is to contribute to the evidence
      base to allow expansion of treatment options for HIV-infected children in low resource
      settings.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-infected child 3 to 5 years of age at time of screening for this trial if enrolled
             from outside or any age if enrolled from control arm of Neverest II.

          -  Reliable history or documented exposure to NVP used as part of PMTCT

          -  Initiated antiretroviral therapy with LPV/r at age less than 36 months

          -  Receiving LPV/r-based ART for at least 12 months

          -  At least one viral load measurement less than 50 copies/ml conducted as part of
             screening for the study

          -  ALT measurement grade I or less (DAIDS Toxicity Tables 2004) (Appendix A). These may
             be repeated until ALTs normalize if necessary.

        Exclusion criteria:

          -  Prior treatment with any NNRTI drug as part of a therapeutic regimen

          -  Substitution of other NRTI drugs (instead of 3TC and D4T which are the standard first
             line regimen) will be allowed.