Treatment Options for Protease Inhibitor-exposed Children

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.

Conditions

• HIV/AIDS
• HIV Infections

Interventions

DRUG

Efavirenz (EFV)

Children are assigned to begin a EFV-based antiretroviral based regimen.

DRUG

Lopinavir/ritonavir (LPV/r)

Children are assigned to stay on their current LPV/r-based antiretroviral regimen.

DRUG

Stavudine (D4T)

Children are assigned to stay on their current antiretroviral regimen which includes D4T.

DRUG

Abacavir (ABC)

Children stop taking D4T and switch to ABC.

Sponsors & Collaborators

• University of Witwatersrand, South Africa

  collaborator OTHER

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  collaborator NIH

• Columbia University

  lead OTHER

Principal Investigators

• Louise Kuhn, PhD · Columbia University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

3 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-07-31

Primary Completion

2014-12-31

Completion

2014-12-31

Countries

• South Africa

Study Locations