Treatment Options for Protease Inhibitor-exposed Children

HIV Infections Clinical Trial

— NEVEREST-III  

Official title:

Treatment Options for Protease Inhibitor-exposed Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01146873
• Other study ID #: AAAE1145
• Status: Completed
• Phase: Phase 3
• First received: June 8, 2010
• Last updated: April 22, 2015
• Start date: July 2010
• Est. completion date: December 2014

Study information

• Verified date: April 2015
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal GovernmentSouth Africa: Human Research Ethics CommitteeSouth Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• HIV/AIDS

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
South Africa	Rahima Moosa Mother and Child Hospital	Johannesburg	Gauteng

Sponsors (3)

Lead Sponsor	Collaborator
Columbia University	National Institutes of Health (NIH), University of Witwatersrand, South Africa

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of maintenance of viral suppression	HIV RNA quantity < 50 copies/ml	through 24 and 48 weeks post randomization	No
Primary	Prevalence of confirmed viral rebound	HIV RNA > 1000 copies/ml twice	through 24 weeks and 48 weeks post randomization	Yes
Secondary	Magnitude of CD4 response, hospital admissions, new stage II or greater clinical conditions		through 48 weeks	No
Secondary	Prevalence of ALT elevations, HDL, LDL, CRP, fat distribution	Drug related toxicities, Including fat distribution and metabolic parameters; Including when co-treated for tuberculosis	through 48 weeks	No
Secondary	Prevalence of child adherence to medication	assessed by pharmacy reconciliation of medications brought back	through 48 weeks	No