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

NCT00988039 | Completed Phase 3 DMC

• 3 other identifiers: U.1228.03.004.00021.01IP_2007_33011_003ISRCTN37737787
• Study Type: interventional
• Target: 1,277
• Locations: 5 countries
• Sites: 14

Brief 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.

Conditions

Human Immunodeficiency Virus; HIV

Keywords

Human Immunodeficiency virus; second line therapy; raltegravir; aluvia; monotherapy; integrase inhibitor; protease inhibitor; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• 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

  week 96

Secondary Outcomes (9)

• Good HIV disease control

  week 144

• Proportion with CD4 cell count >250 cells/mm3

  week 96 and week 144

• Proportion with new or recurrent WHO stage 4 event

  week 96 and week 144

• Proportion of patients with plasma viral load <50 copies

  week 48, week 96 and week 144

• Adverse events

  During trial

Study Arms (3)

bPI + 2NRTIs

ACTIVE COMPARATOR

Drug: Aluvia + 2NRTIs

bPI + raltegravir

EXPERIMENTAL

Drug: Aluvia + raltegravir

bPI monotherapy

EXPERIMENTAL

Drug: Aluvia monotherapy

Interventions

Aluvia + 2NRTIs DRUG

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.

bPI + 2NRTIs

Aluvia + raltegravir DRUG

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

bPI + raltegravir

Aluvia monotherapy DRUG

Aluvia (lopinavir/ritonavir 400mg/100mg) twice daily raltegravir (400mg) twice daily for the first 12 weeks only

bPI monotherapy

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Justine Boles: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (14)

AMPATH Centre at Moi Teaching Referral Hospital

Eldoret, Kenya

Location

University of Malawi

Blantyre, Malawi

Location

Mzuzu Central Hospital

Mzuzu, Malawi

Location

Joint Clinical Research Centre

Fort Portal, Uganda

Location

JCRC

Gulu, Uganda

Location

JCRC

Kabale, Uganda

Location

JCRC

Kakira, Uganda

Location

Infectious Diseases Institute

Kampala, Uganda

Location

Joint Clinical Research Centre

Kampala, Uganda

Location

San Raphael of St Francis Hospital Nsambya

Kampala, Uganda

Location

Joint Clinical Research Centre

Mbale, Uganda

Location

Joint Clinical Research Centre

Mbarara, Uganda

Location

University Teaching Hospital

Lusaka, Zambia

Location

University of Zimbabwe Clinical Research Centre

Harare, Zimbabwe

Location

Related Publications (4)

• Shi Y, Thompson J, Walker AS, Paton NI, Cheung YB; EARNEST Trial Team. Mapping the medical outcomes study HIV health survey (MOS-HIV) to the EuroQoL 5 Dimension (EQ-5D-3 L) utility index. Health Qual Life Outcomes. 2019 May 10;17(1):83. doi: 10.1186/s12955-019-1135-8.

  PMID: 31077251 DERIVED

• Thompson JA, Kityo C, Dunn D, Hoppe A, Ndashimye E, Hakim J, Kambugu A, van Oosterhout JJ, Arribas J, Mugyenyi P, Walker AS, Paton NI; Europe-Africa Research Network for Evaluation of Second-line Therapy (EARNEST) Trial Team. Evolution of Protease Inhibitor Resistance in Human Immunodeficiency Virus Type 1 Infected Patients Failing Protease Inhibitor Monotherapy as Second-line Therapy in Low-income Countries: An Observational Analysis Within the EARNEST Randomized Trial. Clin Infect Dis. 2019 Mar 19;68(7):1184-1192. doi: 10.1093/cid/ciy589.

  PMID: 30060027 DERIVED

• Paton NI, Kityo C, Thompson J, Nankya I, Bagenda L, Hoppe A, Hakim J, Kambugu A, van Oosterhout JJ, Kiconco M, Bertagnolio S, Easterbrook PJ, Mugyenyi P, Walker AS; Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST) Trial Team. Nucleoside reverse-transcriptase inhibitor cross-resistance and outcomes from second-line antiretroviral therapy in the public health approach: an observational analysis within the randomised, open-label, EARNEST trial. Lancet HIV. 2017 Aug;4(8):e341-e348. doi: 10.1016/S2352-3018(17)30065-6. Epub 2017 May 8.

  PMID: 28495562 DERIVED

• Paton NI, Kityo C, Hoppe A, Reid A, Kambugu A, Lugemwa A, van Oosterhout JJ, Kiconco M, Siika A, Mwebaze R, Abwola M, Abongomera G, Mweemba A, Alima H, Atwongyeire D, Nyirenda R, Boles J, Thompson J, Tumukunde D, Chidziva E, Mambule I, Arribas JR, Easterbrook PJ, Hakim J, Walker AS, Mugyenyi P; EARNEST Trial Team. Assessment of second-line antiretroviral regimens for HIV therapy in Africa. N Engl J Med. 2014 Jul 17;371(3):234-47. doi: 10.1056/NEJMoa1311274.

  PMID: 25014688 DERIVED

Related Links

• EARNEST trial website

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

lopinavir-ritonavir drug combination; Raltegravir Potassium

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nicholas Paton, MD FRCP

  MRC CTU

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor Nicholas Paton

Study Record Dates

• First Submitted: September 30, 2009
• First Posted: October 1, 2009
• Study Start: March 1, 2010
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: April 4, 2014

Record last verified: 2014-04

Locations

MA (2); ZA (1); UG (9); ZI (1); KE (1)