A Trial of 2 Options for Second Line Combination Antiretroviral Therapy Following Virological Failure of a Standard Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI)+2N(t)RTI First Line Regimen

NCT00931463 | Completed Phase 4 Results DMC

• 1 other identifier: SECOND-LINE
• Study Type: interventional
• Target: 558
• Locations: 17 countries
• Sites: 44

Brief Summary

The investigators hypothesize that following virological failure of a standard NNRTI+2N(T)RTI regimen second-line antiretroviral therapy consisting of ritonavir-boosted lopinavir and 2N(T)RTIs will offer comparable efficacy to that provided by ritonavir-boosted lopinavir and raltegravir. The study will be conducted for 96-weeks with the primary endpoint analyzed after 48-weeks. The primary endpoint is virological: a comparison of virological suppression in plasma \< 200 copies/mL between the randomized arms after 48 weeks. Secondary and exploratory endpoints include virological, immunological, safety, clinical, metabolic, drug adherence, drug resistance and quality of life.

Conditions

HIV Infections

Keywords

second line therapy; combination antiretroviral therapy; first-line failure; AIDS; treatment experienced

Outcome Measures

Primary Outcomes (1)

• Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization

  48 weeks following randomization

Secondary Outcomes (4)

• Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population

  48 weeks

• Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Non-completer Classed as Failure

  48 weeks

• Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Baseline VL >100,000 Copies Per mL

  48 weeks

• Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, VL Less Than or Equal to 100,000 Copies Per mL

  48 weeks

Study Arms (2)

Ritonavir-boosted lopinavir and 2N(t)RTI

ACTIVE COMPARATOR

This is the current standard of care for second line therapy following failure of standard first-line NNRTI+2N(t)RTIs according to WHO guidelines.

Drug: 2N(t)RTI; Drug: Ritonavir-boosted lopinavir

Ritonavir-boosted lopinavir and raltegravir

EXPERIMENTAL

This is an experimental arm which is likely to be fully active in the presence of N(t)RTI mutations and which preliminary evidence suggests should be potent and durable.

Drug: raltegravir; Drug: Ritonavir-boosted lopinavir

Interventions

raltegravir DRUG

400 mg raltegravir tablet taken every 12 hours

Also known as: Isentress

Ritonavir-boosted lopinavir and raltegravir

2N(t)RTI DRUG

2N(t)RTIs as prescribed

Also known as: nucleosides, nucleotides, nuncleoside backbone

Ritonavir-boosted lopinavir and 2N(t)RTI

Ritonavir-boosted lopinavir DRUG

2 heat-stable tablets of ritonavir-boosted lopinavir taken every 12 hours

Also known as: Aluvia, Kaletra

Ritonavir-boosted lopinavir and 2N(t)RTI; Ritonavir-boosted lopinavir and raltegravir

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 positive by licensed diagnostic test
• Aged 16 years or older (or minimum age as determined by local regulations or as legal requirements dictate)
• Have received first antiretroviral regimen consisting of an NNRTI plus 2N(t)RTIs for at least 24 weeks
• No change in antiretroviral therapy within 12 weeks prior to screening
• Failed first-line NNRTI + 2N(t)RTI combination therapy according to virological criteria defined by two consecutive (at least 7 days apart) HIV RNA results of greater then 500 copies/mL
• No prior or current exposure to HIV protease inhibitors and/or HIV integrase inhibitors
• Able to provide written informed consent

You may not qualify if:

• The following laboratory variables:
• absolute neutrophil count (ANC) \< 500 cells/microlitres
• hemoglobin \< 7.0 g/decilitres
• platelet count \< 50,000 cells/microlitres
• ALT great than 5 x ULN
• Pregnant or nursing mothers
• Participants with active viral hepatitis B infection defined by the presence in serum of hepatitis B surface antigen
• Use of immunomodulators within 30 days prior to screening
• Use of any prohibited medications (rifampicin, midazolam, triazolam, cisapride, pimozide, amiodarone, dihydroergotamine, ergotamine, ergonovine, methylergonovine, astemizole, terfenadine, vardenafil, and St. John's wort)
• Intercurrent illness requiring hospitalization
• Active opportunistic disease not under adequate control in the opinion of the site Principal Investigator
• Participants with current alcohol or illicit substance abuse that in the opinion of the site Principal Investigator might adversely affect participation in the study
• Participants deemed by the site Principal Investigator unlikely to be able to remain in follow-up for the protocol-defined period

Sponsors & Collaborators

• Kirby Institute: lead
• Abbott: collaborator
• Merck Sharp & Dohme LLC: collaborator
• amfAR, The Foundation for AIDS Research: collaborator

Study Sites (44)

Hospital Interzonal General de Agudos, Oscar Alende

Buenos Aires, Mar Del Plata Provincia, 1900, Argentina

Location

CAICI

Buenos Aires, Rosario Provincia de Sante Fe, 2000, Argentina

Location

Hospital General de Agudos 'Teodoro Alvarez'

Buenos Aires, 1406, Argentina

Location

FUNCEI

Buenos Aires, Argentina

Location

Hospital de Infecciosas FJ Muniz

Buenos Aires, Argentina

Location

Hospital Italiano

Buenos Aires, Argentina

Location

Hospital J.M. Ramos Mejia

Buenos Aires, Argentina

Location

Hospital Prof. Alejandro Posadas

Buenos Aires, Argentina

Location

Hospital Rawson

Córdoba, Argentina

Location

Hospital Central

Mendoza, 5500, Argentina

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Albion Street Centre

Sydney, New South Wales, 2010, Australia

Location

St Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Centre Clinic

Melbourne, Victoria, 3182, Australia

Location

Hospital de la Universidad Catolica Pontificia

Santiago, Chile

Location

Hospital San Borja-Arriaran

Santiago, Chile

Location

Hopital Saint-Louis

Paris, France

Location

Medical Group Practice

Berlin, Germany

Location

J W Goethe Universitat

Frankfurt, Germany

Location

Queen Elizabeth Hospital

Hong Kong, Kowloon, Hong Kong

Location

Institute of Infectious Diseases

Pune, Pune, India

Location

YRG Care

Chennai, India

Location

Mater Misericordiae-Dublin

Dublin, Ireland

Location

Hospital Pelau Pinang

Kuala Lumpur, Malaysia

Location

Hospital Sungai Buloh

Kuala Lumpur, Malaysia

Location

University of Malaysia

Kuala Lumpur, Malaysia

Location

Hospital General de Guadalajara

Guadalajara, Mexico

Location

Hospital General de Leon

León, Mexico

Location

Instituto Nacional de Ciencias Medicas y Nutricion "Salvado Zubiran"

Mexico City, Mexico

Location

Auckland Hospital

Grafton, Auckland, 1, New Zealand

Location

Evangel Hospital (ECWA)

Jos, Plateau State, Nigeria

Location

Jos University Teaching Hospital (JUTH)

Jos, Plateau State, Nigeria

Location

Plateau State Specialist Hospital

Jos, Plateau State, Nigeria

Location

Hospital Almenara

Lima, Peru

Location

IMPACTA/Hospital Dos de Mayo

Lima, Peru

Location

Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia

Lima, Peru

Location

Via Libre

Lima, Peru

Location

Tan Tock Seng Hospital

Singapore, 308433, Singapore

Location

Josha Research

Bloemfontein, South Africa

Location

Desmond Tutu HIV Foundation

Cape Town, South Africa

Location

Chris Hani Baragwanath Hospital

Soweto, South Africa

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Chelsea and Westminster Hospital

Fulham, London, SW10 9NH, United Kingdom

Location

Related Publications (4)

• Henry RT, Jiamsakul A, Law M, Losso M, Kamarulzaman A, Phanuphak P, Kumarasamy N, Foulkes S, Mohapi L, Nwizu C, Wood R, Kelleher A, Polizzotto M; SECOND-LINE Study Group. Factors Associated With and Characteristic of HIV/Tuberculosis Co-Infection: A Retrospective Analysis of SECOND-LINE Clinical Trial Participants. J Acquir Immune Defic Syndr. 2021 May 1;87(1):720-729. doi: 10.1097/QAI.0000000000002619.

  PMID: 33399309 DERIVED

• Amin J, Boyd MA, Kumarasamy N, Moore CL, Losso MH, Nwizu CA, Mohapi L, Kerr SJ, Sohn AH, Teppler H, Renjifo B, Molina JM, Emery S, Cooper DA. Raltegravir non-inferior to nucleoside based regimens in second-line therapy with lopinavir/ritonavir over 96 weeks: a randomised open label study for the treatment of HIV-1 infection. PLoS One. 2015 Feb 27;10(2):e0118228. doi: 10.1371/journal.pone.0118228. eCollection 2015.

  PMID: 25723472 DERIVED

• Martin A, Moore CL, Mallon PW, Hoy JF, Emery S, Belloso WH, Phanuphak P, Ferret S, Cooper DA, Boyd MA; Second-Line Study Team. HIV lipodystrophy in participants randomised to lopinavir/ritonavir (LPV/r) +2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTI) or LPV/r + raltegravir as second-line antiretroviral therapy. PLoS One. 2013 Oct 30;8(10):e77138. doi: 10.1371/journal.pone.0077138. eCollection 2013.

  PMID: 24204757 DERIVED

• SECOND-LINE Study Group; Boyd MA, Kumarasamy N, Moore CL, Nwizu C, Losso MH, Mohapi L, Martin A, Kerr S, Sohn AH, Teppler H, Van de Steen O, Molina JM, Emery S, Cooper DA. Ritonavir-boosted lopinavir plus nucleoside or nucleotide reverse transcriptase inhibitors versus ritonavir-boosted lopinavir plus raltegravir for treatment of HIV-1 infection in adults with virological failure of a standard first-line ART regimen (SECOND-LINE): a randomised, open-label, non-inferiority study. Lancet. 2013 Jun 15;381(9883):2091-9. doi: 10.1016/S0140-6736(13)61164-2.

  PMID: 23769235 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Raltegravir Potassium; Nucleosides; Nucleotides; lopinavir-ritonavir drug combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glycosides; Carbohydrates; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Prof Sean Emery
• Organization: The Kirby Institute

semery@kirby.unsw.edu.au

+61293850900

Study Officials

• David A Cooper, MD

  Kirby Institute

  STUDY CHAIR

• Brian Gazzard, MD

  St. Stephen's Trust

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2009
• First Posted: July 2, 2009
• Study Start: September 1, 2009
• Primary Completion: September 1, 2012
• Study Completion: August 1, 2013
• Last Updated: March 27, 2026
• Results First Posted: January 17, 2014

Record last verified: 2019-08

Locations

SG (1); ME (3); ZA (3); IE (1); HK (1); NG (3); GB (1); PE (4); DE (2); AU (5); FR (1); CL (2); TW (1); IN (2); NZ (1); AR (10); MY (3)