Treatment Options for Protease Inhibitor-exposed Children
Status:
Completed
Trial end date:
2014-12-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 3
Details
Lead Sponsor:
Columbia University
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) University of Witwatersrand, South Africa
Treatments:
Abacavir Efavirenz HIV Protease Inhibitors Lopinavir Protease Inhibitors Ritonavir Stavudine