Treatment Options for Protease Inhibitor-exposed Children (NEVEREST-III)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University of Witwatersrand, South Africa
Information provided by (Responsible Party):
Louise Kuhn, Columbia University
ClinicalTrials.gov Identifier:
NCT01146873
First received: June 8, 2010
Last updated: November 18, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
HIV/AIDS
HIV Infections
Drug: Efavirenz
Drug: Lopinavir/ritonavir (LPV/r)
Drug: D4T
Drug: Abacavir (ABC)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment Options for Protease Inhibitor-exposed Children

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Maintenance of viral suppression [ Time Frame: through 24 and 48 weeks post randomization ] [ Designated as safety issue: No ]
    HIV RNA quantity < 50 copies/ml

  • Confirmed viral rebound [ Time Frame: through 24 weeks and 48 weeks post randomization ] [ Designated as safety issue: Yes ]
    HIV RNA > 1000 copies/ml twice


Secondary Outcome Measures:
  • Magnitude of CD4 response, hospital admissions, new stage II or greater clinical conditions [ Time Frame: through 48 weeks ] [ Designated as safety issue: No ]
  • ALT elevations, HDL, LDL, CRP, fat distribution [ Time Frame: through 48 weeks ] [ Designated as safety issue: No ]

    Drug related toxicities, Including fat distribution and metabolic parameters

    Including when co-treated for tuberculosis


  • child Adherence to medication [ Time Frame: through 48 weeks ] [ Designated as safety issue: No ]
    assessed by pharmacy reconciliation of medications brought back


Estimated Enrollment: 400
Study Start Date: June 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1: Lopinavir/ritonavir (LPV/r)
Participants are assigned to remain on their current LPV/r-based antiretroviral regimen
Drug: Lopinavir/ritonavir (LPV/r)
Children are assigned to stay on their current LPV/r-based antiretroviral regimen.Dosing of medication will follow standard guidelines based on body surface area calculations or on body weight depending on drug, and will be in accordance with the South African Treatment guidelines.
Other Names:
  • Efavirenz (EFV)
  • D4T
  • Abacavir (ABC)
Experimental: Group 2: Efavirenz (EFV)
Participants are assigned to switch to an EFV-based antiretroviral regimen
Drug: Efavirenz
Children are assigned to begin a EFV-based antiretroviral based regimen. Dosing of medication will follow standard guidelines based on body surface area calculations or on body weight depending on drug, and will be in accordance with the South African Treatment guidelines.
Other Names:
  • Lopinavir/ritonavir (LPV/r
  • D4T
  • Abacavir (ABC)
Active Comparator: Group D: D4T
Children are assigned to remain on their current antiretroviral regimen, which includes D4T
Drug: D4T
Children are assigned to stay on their current antiretroviral regimen which includes D4T. Dosing of medication will follow standard guidelines based on body surface area calculations or on body weight depending on drug, and will be in accordance with the South African Treatment guidelines.
Other Names:
  • Lopinavir/ritonavir (LPV/r)
  • Efavirenz (EFV)
  • Abacavir (ABC)
Experimental: Group A: Abacavir (ABC)
Children stop taking D4T and switch to ABC.
Drug: Abacavir (ABC)
Children stop taking D4T and switch to an abacavir. Dosing of medication will follow standard guidelines based on body surface area calculations or on body weight depending on drug, and will be in accordance with the South African Treatment guidelines.
Other Names:
  • Lopinavir/ritonavir (LPV/r)
  • Efavirenz (EFV)
  • D4T

  Eligibility

Ages Eligible for Study:   3 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01146873

Locations
South Africa
Rahima Moosa Mother and Child Hospital
Johannesburg, Gauteng, South Africa
Sponsors and Collaborators
Columbia University
University of Witwatersrand, South Africa
Investigators
Principal Investigator: Louise Kuhn, PhD Columbia University
  More Information

No publications provided

Responsible Party: Louise Kuhn, Professor, Columbia University
ClinicalTrials.gov Identifier: NCT01146873     History of Changes
Other Study ID Numbers: AAAE1145
Study First Received: June 8, 2010
Last Updated: November 18, 2012
Health Authority: United States: Institutional Review Board
United States: Federal Government
South Africa: Human Research Ethics Committee
South Africa: Medicines Control Council

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Abacavir
Efavirenz
HIV Protease Inhibitors
Lopinavir
Protease Inhibitors
Ritonavir
Stavudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014