Treatment Options for Protease Inhibitor-exposed Children
NEVEREST-III
2 other identifiers
interventional
300
1 country
1
Study Start
July 2010
Date type not reportedThis date has not been verified as actual or estimated.
Primary Completion
December 2014
Actual (reported)Study Completion
December 2014
Actual (reported)Brief 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.
Registry Overview
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
- Recruitment status
- completed
- Actual enrollment (reported)
- 300 participants
- Study completion date
December 2014
Actual (reported)- Listed locations
- 1 countries · 1 sites
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
First Submitted
June 8, 2010
Actual (reported)First Posted
June 22, 2010
Actual (reported)Study Start
July 2010
Date type not reportedThis date has not been verified as actual or estimated.
Primary Completion
December 2014
Actual (reported)Study Completion
December 2014
Actual (reported)Results Posted
May 4, 2016
Actual (reported)
- Last Updated
- March 13, 2017
- Status Verified
- January 2017
- Results QC Date
- February 29, 2016
- Last Update Submitted
- January 31, 2017
Conditions
Outcome Measures
Primary Outcomes (2)
Viral Rebound
Probability of viral rebound defined as \>=1 HIV RNA measurements \>50 copies/ml using survival analysis by 48 weeks post-randomization.
48 weeks
Viral Failure
Probability of viral failure defined as \>= 2 HIV RNA measurements \>1000 copies/ml using survival analysis by 48 weeks post-randomization.
48 weeks
Secondary Outcomes (3)
CD4 Cell Percentage at 48 Weeks After Randomization
48 weeks
Percentage of Participants With Elevated Total Cholesterol, Elevated LDL, Abnormal HDL, or Abnormal Triglycerides at 40 Weeks After Randomization
40 weeks
Highest Grade ALT After Randomization
through 48 weeks post randomization
Study Arms (4)
Group 1: Lopinavir/ritonavir (LPV/r)
ACTIVE COMPARATORParticipants are assigned to remain on their current LPV/r-based antiretroviral regimen. Ritonavir-boosted lopinavir syrup was given twice per day at 230 mg/m\^2 per dose. Children able to swallow tablets were given 1 tablet twice per day (200 mg lopinavir/50 mg ritonavir) if body surface area was less than 0.9m\^2 or 2 tablets twice per day if body surface area was 0.9m\^2 or higher.
Group 2: Efavirenz (EFV)
EXPERIMENTALParticipants are assigned to switch to an EFV-based antiretroviral regimen. Efavirenz was prescribed once daily in the evening at 200 mg for weights of 10 kg to 13.9 kg (22-30 lb) and 300mg for weights of 14 kg to 24.9 kg (31-55 lb). Efavirenz was available in 50-mg and 200-mg capsules. If children were unable to swallow capsules, caregivers were shown how to open the capsules and dissolve the contents in water.
Group D: Stavudine (D4T)
ACTIVE COMPARATORChildren are assigned to remain on their current antiretroviral regimen, which includes D4T. D4T was given at 1 mg/kg twice daily
Group A: Abacavir (ABC)
EXPERIMENTALChildren stop taking D4T and switch to ABC. ABC was given at 8 mg/kg twice daily.
Interventions
Children are assigned to begin a EFV-based antiretroviral based regimen.
Children are assigned to stay on their current LPV/r-based antiretroviral regimen.
Children are assigned to stay on their current antiretroviral regimen which includes D4T.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Rahima Moosa Mother and Child Hospital
Johannesburg, Gauteng, South Africa
Related Publications (2)
Coovadia A, Abrams EJ, Strehlau R, Shiau S, Pinillos F, Martens L, Patel F, Hunt G, Tsai WY, Kuhn L. Efavirenz-Based Antiretroviral Therapy Among Nevirapine-Exposed HIV-Infected Children in South Africa: A Randomized Clinical Trial. JAMA. 2015 Nov 3;314(17):1808-17. doi: 10.1001/jama.2015.13631.
PMID: 26529159RESULTMurnane PM, Strehlau R, Shiau S, Patel F, Mbete N, Hunt G, Abrams EJ, Coovadia A, Kuhn L. Switching to Efavirenz Versus Remaining on Ritonavir-boosted Lopinavir in Human Immunodeficiency Virus-infected Children Exposed to Nevirapine: Long-term Outcomes of a Randomized Trial. Clin Infect Dis. 2017 Aug 1;65(3):477-485. doi: 10.1093/cid/cix335.
PMID: 28419200DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Louise Kuhn, PhD
- Organization
- Columbia University
Study Officials
- PRINCIPAL INVESTIGATOR
Louise Kuhn, PhD
Columbia University
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Enrollment
300 participants — actual enrollment reported by the registry.
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
June 8, 2010
First Posted
June 22, 2010
Study Start
July 2010
Date type not reportedThis date has not been verified as actual or estimated.
Primary Completion
December 2014
Actual (reported)Study Completion
December 2014
Actual (reported)Last Updated
March 13, 2017
Results First Posted
May 4, 2016
Record last verified: 2017-01