NCT01146873‐NEVEREST 3.

Trial name or title	Treatment Options for Protease Inhibitor‐exposed Children (NEVEREST‐III)
Methods	Phase 3 Open label Randomized Efficacy Study (Factorial Assignment)
Participants	400 HIV‐infected children Inclusion criteria: ‐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.
Interventions	‐ Active Comparator A: Group 1: Lopinavir/ritonavir (LPV/r) Participants are assigned to remain on their current LPV/r‐based antiretroviral regimen ‐ Experimental A: Group 2: Efavirenz (EFV) Participants are assigned to switch to an EFV‐based antiretroviral regimen ‐ Active Comparator B: Group D: D4T Children are assigned to remain on their current antiretroviral regimen, which includes D4T ‐ Experimental B: Group A: Abacavir (ABC) Children stop taking D4T and switch to ABC.
Outcomes	Primary Outcome Measures: ‐ Maintenance of viral suppression through 24 and 48 weeks post randomization (HIV RNA<50 copies/ml) ‐ Confirmed viral rebound through 24 weeks and 48 weeks post randomization (HIV RNA>1000 copies/ml) Secondary Outcome Measures: ‐ Magnitude of CD4 response, hospital admissions, new stage II or greater clinical conditions through 48 weeks ‐ ALT elevations, HDL, LDL, CRP, fat distribution through 48 weeks ‐ Drug related toxicities, including fat distribution and metabolic parameters, including when co‐treated for tuberculosis ‐ Adherence to medication through 48 weeks (assessed by pharmacy reconciliation of medications brought back)
Starting date	June 2010 (expected completion September 2014)
Contact information	Louise Kuhn lk24@columbia.edu
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