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

June 8, 2010
November 18, 2012
June 2010
December 2014   (final data collection date for primary outcome measure)
  • 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
Same as current
Complete list of historical versions of study NCT01146873 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Treatment Options for Protease Inhibitor-exposed Children
Treatment Options for Protease Inhibitor-exposed Children

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV/AIDS
  • HIV Infections
  • 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)
  • 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)
  • 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)
  • 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
  • Active Comparator: Group 1: Lopinavir/ritonavir (LPV/r)
    Participants are assigned to remain on their current LPV/r-based antiretroviral regimen
    Intervention: Drug: Lopinavir/ritonavir (LPV/r)
  • Experimental: Group 2: Efavirenz (EFV)
    Participants are assigned to switch to an EFV-based antiretroviral regimen
    Intervention: Drug: Efavirenz
  • Active Comparator: Group D: D4T
    Children are assigned to remain on their current antiretroviral regimen, which includes D4T
    Intervention: Drug: D4T
  • Experimental: Group A: Abacavir (ABC)
    Children stop taking D4T and switch to ABC.
    Intervention: Drug: Abacavir (ABC)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
400
December 2014
December 2014   (final data collection date for primary outcome measure)

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.
Both
3 Years and older
No
Contact information is only displayed when the study is recruiting subjects
South Africa
 
NCT01146873
AAAE1145
Yes
Louise Kuhn, Columbia University
Columbia University
  • University of Witwatersrand, South Africa
  • National Institutes of Health (NIH)
Principal Investigator: Louise Kuhn, PhD Columbia University
Columbia University
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP