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

Not Applicable

Completed

• Conditions: Infections and Infestations; Human immunodeficiency virus; Human immunodeficiency virus (HIV)

• Registration Number: ISRCTN37737787
• Lead Sponsor: Medical Research Council (MRC) (UK)

Brief Summary

2014 Results article in http://www.ncbi.nlm.nih.gov/pubmed/25014688 results 2017 Results article in http://www.ncbi.nlm.nih.gov/pubmed/28495562 observational analysis results 2018 Results article in http://www.ncbi.nlm.nih.gov/pubmed/29108797 follow-up results 2023 Other publications in https://pubmed.ncbi.nlm.nih.gov/36723505/ Substudy results (added 02/02/2023)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-09-22
• Study Completion: 2013-09-15
• Last Update Posted: 13 February 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

1. Previously documented HIV infection on at least one standard antibody-based test
2. Aged 12 years and above, either sex
3. Taking 2NRTI + NNRTI-based regimen continuously for at least 12 months
4. Naive to protease inhibitor therapy
5. Good adherence to anti-retroviral therapy (ART) in the 12 weeks prior to screening defined as no more than 10% of doses missed (patients who do not have good adherence should be given adherence
counselling and re-assessed after an appropriate time interval of not less than 4 weeks)
6. Clinically stable and receiving treatment for any known opportunistic infections
7. HIV treatment failure defined by the one or more of the following clinical, immunological and virological criteria (modified from World Health Organization [WHO] 2006 criteria):
7.1. Clinical: A1 and A2 and A3 must be fulfilled:
A1: New or recurrent WHO stage 4 condition occurring after at least 12 months on ART
A2: CD4 cell count less than 200 cells/mm^3 after at least 12 months on ART, and confirmed at screening
A3: Viral load (VL) greater than 400 copies/ml at screening
7.2. Immunological: (B1 or B2 or B3) and B4 must be fulfilled:
B1: Fall of CD4 count to pre-therapy baseline (or below) after at least 12 months on ART and confirmed at screening
B2: Fall of CD4 count from previous value greater than 400 cells on treatment (x 2) to less than 200 cells/mm3 after at least 12 months on ART and confirmed at screening
B3: CD4 count less than 100 cells after at least 12 months on ART and confirmed at screening
B4: VL greater than 400 copies/ml at screening
7.3. Virological: VL greater than 10,000 copies/ml after at least 6 months on ART, and confirmed at screening after at least 12 months on ART
8. Willing and able to provide written informed consent
9. Able to attend for regular study follow-up visits

Exclusion Criteria

1. Any major clinical contraindications to the use of bPI, the NRTIs that are available to be selected for a second-line regimen, or raltegravir
2. Known Hepatitis B carrier (Hepatitis B surface antigen positive)
3. Requirement for concomitant medication with known major interactions with study drugs for which drug substitutions or dose alterations are not available or acceptable
4. Currently receiving chemotherapy for malignancy
5. Women who are currently pregnant or breastfeeding
6. Current participation in another clinical trial involving a treatment intervention (may be permitted in some circumstances, but must first be discussed with the EARNEST chief investigator)
7. Life expectancy of less than one month in the opinion of the treating physician

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Good HIV disease control defined as a composite endpoint consisting of all of:<br> 1. No new WHO Stage 4 events between randomisation and week 96, and<br> 2. CD4 count greater than 250 cells/mm3 at week 96, and<br> 3. VL less than 10,000 copies/ml or greater than 10,000 copies/ml with no PI resistance mutations at week 96<br>

Secondary Outcome Measures

Name	Time	Method
<br> 1. Good HIV disease control at week 144<br> 2. Proportion with CD4 cell count greater than 250 cells/mm3 at week 96 and week 144<br> 3. Proportion with new or recurrent WHO Stage 4 event by week 96 and week 144<br> 4. Proportion of patients with plasma VL less than 50 copies at week 48, week 96 and week 144<br> 5. Adverse events (AEs)<br> 6. Quality of life change from randomisation<br> 7. Neurocognitive function change from randomisation<br> 8. Healthcare costs<br>