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 (SECOND-LINE)

March 12, 2026 updated by: Kirby Institute

A Randomised Open-label Study Comparing the Safety and Efficacy of Ritonavir Boosted Lopinavir and 2-3N(t)RTI Backbone Versus Ritonavir Boosted Lopinavir and Raltegravir in Participants Virologically Failing First-line NNRTI/2N(t)RTI Therapy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In HIV-infected subjects who have virologically failed first-line antiretroviral therapy comprising 2N(t)RTI + NNRTI a regimen of second-line therapy incorporating ritonavir-boosted lopinavir and raltegravir provides comparable (i.e., non-inferior) antiretroviral efficacy over 48 weeks to a regimen containing ritonavir-boosted lopinavir and 2-3N(t)RTIs.

Eligible patients will be randomised to one of two arms:

I. ritonavir boosted lopinavir (LPV/r) 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3N(t)RTIs

II. ritonavir boosted lopinavir (LPV/r) 200mg/50mg 4 tabs once daily or 2 tabs twice daily + raltegravir 400 mg twice daily

The primary objective of this study is to compare the virological efficacy of the two strategies as measured by the proportion of participants with HIV RNA < 200 copies/mL 48 weeks after randomisation.

Secondary objectives include virological, immunological, safety and antiretroviral therapy endpoints.

Exploratory endpoints include clinical, metabolic, drug resistance, medication adherence and quality of life endpoints.

Study Type

Interventional

Enrollment (Actual)

558

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Hospital Italiano
      • Buenos Aires, Argentina
        • FUNCEI
      • Buenos Aires, Argentina, 1406
        • Hospital General de Agudos 'Teodoro Alvarez'
      • Buenos Aires, Argentina
        • Hospital de Infecciosas FJ Muniz
      • Buenos Aires, Argentina
        • Hospital J.M. Ramos Mejia
      • Buenos Aires, Argentina
        • Hospital Prof. Alejandro Posadas
      • Córdoba, Argentina
        • Hospital Rawson
      • Mendoza, Argentina, 5500
        • Hospital Central
    • Mar Del Plata Provincia
      • Buenos Aires, Mar Del Plata Provincia, Argentina, 1900
        • Hospital Interzonal General de Agudos, Oscar Alende
    • Rosario Provincia de Sante Fe
      • Buenos Aires, Rosario Provincia de Sante Fe, Argentina, 2000
        • CAICI
  • Australia
    • New South Wales
      • Liverpool, New South Wales, Australia, 2170
        • Liverpool Hospital
      • Sydney, New South Wales, Australia, 2010
        • St Vincent's Hospital
      • Sydney, New South Wales, Australia, 2010
        • Albion Street Centre
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • The Alfred Hospital
      • Melbourne, Victoria, Australia, 3182
        • Centre Clinic
  • Chile
      • Santiago, Chile
        • Hospital de la Universidad Catolica Pontificia
      • Santiago, Chile
        • Hospital San Borja-Arriaran
  • France
      • Paris, France
        • Hôpital Saint-Louis
  • Germany
      • Berlin, Germany
        • Medical Group Practice
      • Frankfurt, Germany
        • J W Goethe Universitat
  • Hong Kong
    • Kowloon
      • Hong Kong, Kowloon, Hong Kong
        • Queen Elizabeth Hospital
  • India
      • Chennai, India
        • YRG Care
    • Pune
      • Pune, Pune, India
        • Institute of Infectious Diseases
  • Ireland
      • Dublin, Ireland
        • Mater Misericordiae-Dublin
  • Malaysia
      • Kuala Lumpur, Malaysia
        • Hospital Pelau Pinang
      • Kuala Lumpur, Malaysia
        • Hospital Sungai Buloh
      • Kuala Lumpur, Malaysia
        • University of Malaysia
  • Mexico
      • Guadalajara, Mexico
        • Hospital General de Guadalajara
      • León, Mexico
        • Hospital General de Leon
      • Mexico City, Mexico
        • Instituto Nacional de Ciencias Medicas y Nutricion "Salvado Zubiran"
  • New Zealand
    • Auckland
      • Grafton, Auckland, New Zealand, 1
        • Auckland Hospital
  • Nigeria
    • Plateau State
      • Jos, Plateau State, Nigeria
        • Evangel Hospital (ECWA)
      • Jos, Plateau State, Nigeria
        • Jos University Teaching Hospital (JUTH)
      • Jos, Plateau State, Nigeria
        • Plateau State Specialist Hospital
  • Peru
      • Lima, Peru
        • Hospital Almenara
      • Lima, Peru
        • IMPACTA/Hospital Dos de Mayo
      • Lima, Peru
        • Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia
      • Lima, Peru
        • Via Libre
  • Singapore
      • Singapore, Singapore, 308433
        • Tan Tock Seng Hospital
  • South Africa
      • Bloemfontein, South Africa
        • Josha Research
      • Cape Town, South Africa
        • Desmond Tutu HIV Foundation
      • Soweto, South Africa
        • Chris Hani Baragwanath Hospital
  • Taiwan
      • Taipei, Taiwan
        • National Taiwan University Hospital
  • United Kingdom
    • London
      • Fulham, London, United Kingdom, SW10 9NH
        • Chelsea and Westminster Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. HIV-1 positive by licensed diagnostic test
  2. Aged 16 years or older (or minimum age as determined by local regulations or as legal requirements dictate)
  3. Have received first antiretroviral regimen consisting of an NNRTI plus 2N(t)RTIs for at least 24 weeks
  4. No change in antiretroviral therapy within 12 weeks prior to screening
  5. 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
  6. No prior or current exposure to HIV protease inhibitors and/or HIV integrase inhibitors
  7. Able to provide written informed consent

Exclusion Criteria:

  1. 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
  2. Pregnant or nursing mothers
  3. Participants with active viral hepatitis B infection defined by the presence in serum of hepatitis B surface antigen
  4. Use of immunomodulators within 30 days prior to screening
  5. Use of any prohibited medications (rifampicin, midazolam, triazolam, cisapride, pimozide, amiodarone, dihydroergotamine, ergotamine, ergonovine, methylergonovine, astemizole, terfenadine, vardenafil, and St. John's wort)
  6. Intercurrent illness requiring hospitalization
  7. Active opportunistic disease not under adequate control in the opinion of the site Principal Investigator
  8. Participants with current alcohol or illicit substance abuse that in the opinion of the site Principal Investigator might adversely affect participation in the study
  9. Participants deemed by the site Principal Investigator unlikely to be able to remain in follow-up for the protocol-defined period

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Ritonavir-boosted lopinavir and 2N(t)RTI
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
2N(t)RTIs as prescribed
Other Names:
  • nucleosides, nucleotides, nuncleoside backbone
Drug: Ritonavir-boosted lopinavir
2 heat-stable tablets of ritonavir-boosted lopinavir taken every 12 hours
Other Names:
  • Aluvia, Kaletra
Experimental: Ritonavir-boosted lopinavir and raltegravir
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: Ritonavir-boosted lopinavir
2 heat-stable tablets of ritonavir-boosted lopinavir taken every 12 hours
Other Names:
  • Aluvia, Kaletra
Drug: raltegravir
400 mg raltegravir tablet taken every 12 hours
Other Names:
  • Isentress

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization
Time Frame: 48 weeks following randomization
48 weeks following randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population
Time Frame: 48 weeks
The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
48 weeks
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Non-completer Classed as Failure
Time Frame: 48 weeks

The non-completer classed as failure analysis will include all randomised participants; participants who meet the following criteria will be defined as failures:

i. week 48 HIV RNA being above each threshold ii. has missing HIV-1 RNA data for any reason iii. stops randomly assigned therapy
48 weeks
Participants With Plasma HIV RNA < 200 Copies/mL 48 Weeks After Randomization, Per-protocol Population, Baseline VL >100,000 Copies Per mL
Time Frame: 48 weeks
The difference between treatment arms in proportion of participants with plasma HIV RNA < 200 copies/mL 48 weeks after randomization, per-protocol population: stratified analysis by baseline plasma viral load (less than or equal to 100,000 copies per mL or >100,000 copies per mL) on those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
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
Time Frame: 48 weeks
The per- protocol population includes those participants who fulfil the protocol in the terms of the eligibility, interventions, and outcome assessment
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kirby Institute

Collaborators

Merck Sharp & Dohme LLC
amfAR, The Foundation for AIDS Research
Abbott

Investigators

  • Study Chair: David A Cooper, MD, Kirby Institute
  • Study Chair: Brian Gazzard, MD, St. Stephen's Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

September 1, 2012

Study Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

July 1, 2009

First Submitted That Met QC Criteria

July 1, 2009

First Posted (Estimated)

July 2, 2009

Study Record Updates

Last Update Posted (Actual)

March 27, 2026

Last Update Submitted That Met QC Criteria

March 12, 2026

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SECOND-LINE

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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