Bone and Body Comp: A Sub Study of the SECOND-LINE Study

NCT01513122 | Completed Phase 4 Results DMC

• 1 other identifier: 2L body comp sub-study
• Study Type: interventional
• Target: 210
• Locations: 5 countries
• Sites: 7

Brief Summary

The use of anti HIV drugs (ART), and in particular a class of drugs known as nucleoside reverse transcriptase inhibitors (N(t)RTI), has been associated with changes in body fat and in particular loss of peripheral fat in the limbs. Low bone mineral density and osteoporosis are also common in HIV-infected patients. There appears to be some association between ART and bone loss, but this is poorly understood and requires further research. The SECOND-LINE study provides an opportunity to examine if a new anti-HIV drug (raltegravir) can result in greater increase in limb fat than a drug regimen containing N(t)RTI, which is currently standard of care. This study also provides an opportunity to examine if additional bone loss occurs with the second regimen of anti-HIV drugs and whether non-N(t)RTI regimens of ART used in second line therapy result in more or less bone loss than use of other classes of anti-HIV drugs such as protease inhibitors or N(t)RTI combinations. It is hypothesized that subjects randomised into Raltegravir arm will demonstrate greater increases in limb fat and smaller reductions in bone density at the proximal femur over 48 weeks than those randomised into the control arm (LPV/r + 2-3N(t)RTIs).

Conditions

HIV

Outcome Measures

Primary Outcomes (2)

• Mean Bone Mineral Density Changes From Baseline to 48 Weeks as Measured by DXA Scan

  48 weeks

• Mean Limbs Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan

  48 weeks

Secondary Outcomes (4)

• Mean Total Body Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan

  48 weeks

• Mean Triglycerides Changes From Baseline to 48 Weeks

  48 weeks

• Mean Total Cholesterol Changes From Baseline to 48 Weeks

  48 weeks

• Mean Glucose Changes From Baseline to 48 Weeks

  48 weeks

Study Arms (2)

Arm 1. Lopinavir / ritonavir + 2-3N(t)RTI

ACTIVE COMPARATOR

LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3N(t)RTI

Drug: Lopinavir / ritonavir; Drug: 2-3N(t)RTI

Arm 2. Lopinavir /ritonavir + raltegravir

ACTIVE COMPARATOR

Drug: Lopinavir / ritonavir; Drug: raltegravir

Interventions

Lopinavir / ritonavir DRUG

LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily

Arm 1. Lopinavir / ritonavir + 2-3N(t)RTI; Arm 2. Lopinavir /ritonavir + raltegravir

2-3N(t)RTI DRUG

Arm 1. Lopinavir / ritonavir + 2-3N(t)RTI

raltegravir DRUG

raltegravir 400mg 1 tablet twice daily.

Arm 2. Lopinavir /ritonavir + 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 ≥ 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 (≥7 days apart) HIV RNA results of \> 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/µL
• hemoglobin \< 7.0 g/dL
• platelet count \< 50,000 cells/µL
• ALT \> 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 hospitalisation
• 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

Study Sites (7)

CEADI

Buenos Aires, Argentina

Location

YRGCare Medical Centre

Chennai, 600113, India

Location

University of Malaya Medical Centre

Kuala Lumpur, 50603, Malaysia

Location

JOSHA Research

Bloemfontein, South Africa

Location

Desmond Tutu HIV Foundation

Cape Town, 7925, South Africa

Location

Chris Hani Baragwanath Hospital

Soweto, South Africa

Location

HIV-NAT Program on AIDS - Thai Red Cross

Bangkok, 10330, Thailand

Location

Related Publications (3)

• Martin A, Moore C, Mallon PW, Hoy J, Emery S, Belloso W, Phanuphak P, Ferret S, Cooper DA, Boyd MA; Second Line study team. Bone mineral density in HIV participants randomized to raltegravir and lopinavir/ritonavir compared with standard second line therapy. AIDS. 2013 Sep 24;27(15):2403-11. doi: 10.1097/01.aids.0000432534.47217.b4.

  PMID: 23921615 RESULT

• 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 RESULT

• Boyd MA, Amin J, Mallon PW, Kumarasamy N, Lombaard J, Wood R, Chetchotisakd P, Phanuphak P, Mohapi L, Azwa I, Belloso WH, Molina JM, Hoy J, Moore CL, Emery S, Cooper DA; SECOND-LINE Study Group. Body composition and metabolic outcomes after 96 weeks of treatment with ritonavir-boosted lopinavir plus either nucleoside or nucleotide reverse transcriptase inhibitors or raltegravir in patients with HIV with virological failure of a standard first-line antiretroviral therapy regimen: a substudy of the randomised, open-label, non-inferiority SECOND-LINE study. Lancet HIV. 2017 Jan;4(1):e13-e20. doi: 10.1016/S2352-3018(16)30189-8. Epub 2016 Nov 1.

  PMID: 27815068 DERIVED

MeSH Terms

Interventions

Lopinavir; Raltegravir Potassium

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

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

semery@kirby.unsw.edu.au

+61293850900

Study Officials

• Paddy Mallon

  Mater Misericordiae University Hospital, Dublin

  PRINCIPAL INVESTIGATOR

• Waldo Belloso

  Hospital Italiano, Argentina

  PRINCIPAL INVESTIGATOR

• Samuel Ferret

  Hopital Saint-Louis, France

  PRINCIPAL INVESTIGATOR

• Praphan Phanuphak

  HIV-NAT Program on AIDS - Thai Red Cross, Bangkok

  PRINCIPAL INVESTIGATOR

• Jennifer Hoy

  The Alfred

  PRINCIPAL INVESTIGATOR

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: January 16, 2012
• First Posted: January 20, 2012
• Study Start: February 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: August 1, 2013
• Last Updated: June 26, 2025
• Results First Posted: January 17, 2014

Record last verified: 2025-06

Locations

MY (1); AR (1); ZA (3); TH (1); IN (1)