NCT00988039

Europe-Africa Research Network for Evaluation of Second-line Therapy

A Randomised Controlled Trial to Evaluate Options for Second-line Therapy in Patients Failing a First-line 2NRTI + NNRTI Regimen in Africa

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,277 (actual)
• Sponsor: Justine Boles · Other Government
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

The trial aim is to ascertain what, if anything, needs to be combined with a boosted protease inhibitor (bPI) backbone in second-line therapy in order to maximize the chance of a good clinical outcome following WHO-defined failure on a first-line nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI-containing regimen with probable extensive NRTI and NNRTI resistance mutations.

Detailed description

The standard of care for second-line HIV therapy in patients who have failed a first-line NNRTI-based regimen is to combine a boosted protease inhibitor (bPI) with two (new) NRTIs. However, patients failing first-line therapy in roll-out programmes often have extensive NRTI resistance mutations that may compromise the efficacy of the NRTI drugs used in second-line therapy and it is likely that the virological potency of the second-line regimen is mostly due to the bPI. It is possible that the contribution of the NRTI drugs to efficacy may be outweighed by additional toxicity and cost. It is also possible that replacing the NRTI drugs with a new class of drug (integrase inhibitors) will improve outcome from second-line therapy, although if the boosted protease inhibitor alone is providing close to optimal response, incremental gains from adding a new class may be small. The principal aims are to determine whether, in patients failing a first-line NRTI and NNRTI-containing regimen: * The use of bPI plus raltegravir (an integrase inhibitor) is superior to standard of care (bPI plus 2 new NRTIs) in achieving good HIV disease control at 96 weeks after randomisation * The use of bPI monotherapy, preceded by a 12-week induction period in combination with raltegravir, is non-inferior to standard of care in achieving good HIV disease control at 96 weeks after randomisation

Conditions

• Human Immunodeficiency Virus
• HIV

Interventions

Type	Name	Description
DRUG	Aluvia + 2NRTIs	Aluvia (lopinavir/ritonavir 400mg/100mg), twice daily The choice of NRTIs will be at the discretion of the managing clinician and based on the local standard of care and drug availability, taking into account patient's previous drug exposure and side effects on first-line therapy.
DRUG	Aluvia + raltegravir	Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily raltegravir (400mg) twice daily
DRUG	Aluvia monotherapy	Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily raltegravir (400mg) twice daily for the first 12 weeks only

Timeline

• Start date: 2010-03-01
• Primary completion: 2014-01-01
• Completion: 2014-01-01
• First posted: 2009-10-01
• Last updated: 2014-04-04

Locations

14 sites across 5 countries: Kenya, Malawi, Uganda, Zambia, Zimbabwe