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Europe-Africa Research Network for Evaluation of Second-line Therapy (EARNEST)

This study has been completed.
European and Developing Countries Clinical Trials Partnership (EDCTP)
Information provided by (Responsible Party):
Justine Boles, Medical Research Council Identifier:
First received: September 30, 2009
Last updated: April 3, 2014
Last verified: April 2014
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.

Condition Intervention Phase
Human Immunodeficiency Virus
Drug: Aluvia + 2NRTIs
Drug: Aluvia + raltegravir
Drug: Aluvia monotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Controlled Trial to Evaluate Options for Second-line Therapy in Patients Failing a First-line 2NRTI + NNRTI Regimen in Africa

Resource links provided by NLM:

Further study details as provided by Medical Research Council:

Primary Outcome Measures:
  • Good HIV disease control defined as a composite endpoint consisting of all of: - No new WHO stage 4 events - CD4 count >250 cells/mm3 - viral load <10,000 copies/ml or >10,000 copies/ml with no PI resistance mutations [ Time Frame: week 96 ]

Secondary Outcome Measures:
  • Good HIV disease control [ Time Frame: week 144 ]
  • Proportion with CD4 cell count >250 cells/mm3 [ Time Frame: week 96 and week 144 ]
  • Proportion with new or recurrent WHO stage 4 event [ Time Frame: week 96 and week 144 ]
  • Proportion of patients with plasma viral load <50 copies [ Time Frame: week 48, week 96 and week 144 ]
  • Adverse events [ Time Frame: During trial ]
  • Quality of life change from randomisation [ Time Frame: During trial ]
  • Neurocognitive function change from randomisation [ Time Frame: during trial ]
  • Healthcare costs [ Time Frame: During trial ]
  • Proportion with serious non-AIDS events [ Time Frame: Week 96 and week 144 ]

Enrollment: 1277
Study Start Date: March 2010
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: bPI + 2NRTIs 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.

Experimental: bPI + raltegravir Drug: Aluvia + raltegravir

Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily

raltegravir (400mg) twice daily

Experimental: bPI monotherapy Drug: Aluvia monotherapy

Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily

raltegravir (400mg) twice daily for the first 12 weeks only

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

Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Previously documented HIV infection on at least one standard antibody-based test
  • Age 12 years and above
  • Taking 2NRTI + NNRTI-based regimen continuously for at least 12 months
  • Naive to protease inhibitor therapy
  • Good adherence to ART in the 12 weeks prior to screening defined as missing medication on no more than 3 days in the prior month
  • Clinically stable and receiving treatment for any known opportunistic infections
  • HIV treatment failure defined by one or more of clinical, immunological or virological criteria defined in the protocol, including VL and CD4 at screening visit
  • Willing and able to give informed consent
  • Able to attend for regular study follow up visits

Exclusion Criteria:

  • Any major clinical contra-indications to the use of bPI, the NRTIs that are available to be selected for a second-line regimen or raltegravir
  • Known Hepatitis B carrier (Hepatitis B surface antigen positive if tested)
  • Requires concomitant medication with known major interactions with study drugs for which drug substitutions or dose alterations are not available or acceptable
  • Women who are currently pregnant or breastfeeding
  • Current participation in another clinical trial involving a treatment intervention (may be permitted in some circumstances, but must be discussed with MRC CTU)
  • Life expectancy of less than one month in the opinion of the treating physician
  Contacts and Locations
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Please refer to this study by its identifier: NCT00988039

AMPATH Centre at Moi Teaching Referral Hospital
Eldoret, Kenya
University of Malawi
Blantyre, Malawi
Mzuzu Central Hospital
Mzuzu, Malawi
Joint Clinical Research Centre
Fort Portal, Uganda
Gulu, Uganda
Kabale, Uganda
Kakira, Uganda
Infectious Diseases Institute
Kampala, Uganda
Joint Clinical Research Centre
Kampala, Uganda
San Raphael of St Francis Hospital Nsambya
Kampala, Uganda
Joint Clinical Research Centre
Mbale, Uganda
Joint Clinical Research Centre
Mbarara, Uganda
University Teaching Hospital
Lusaka, Zambia
University of Zimbabwe Clinical Research Centre
Harare, Zimbabwe
Sponsors and Collaborators
Justine Boles
European and Developing Countries Clinical Trials Partnership (EDCTP)
Study Director: Nicholas Paton, MD FRCP MRC CTU
  More Information

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Justine Boles, Professor Nicholas Paton, Medical Research Council Identifier: NCT00988039     History of Changes
Other Study ID Numbers: U.1228.03.004.00021.01
Study First Received: September 30, 2009
Last Updated: April 3, 2014

Keywords provided by Medical Research Council:
Human Immunodeficiency virus
second line therapy
integrase inhibitor
protease inhibitor
Randomized Controlled Trial

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Raltegravir Potassium
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors processed this record on April 28, 2017