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

NCT ID: NCT01513122

Last Updated: 2025-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2013-08-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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

Group Type: ACTIVE_COMPARATOR

Lopinavir / ritonavir

Intervention Type: DRUG

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

2-3N(t)RTI

Intervention Type: DRUG

Arm 2. Lopinavir /ritonavir + raltegravir

Group Type: ACTIVE_COMPARATOR

Lopinavir / ritonavir

Intervention Type: DRUG

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

raltegravir

Intervention Type: DRUG

raltegravir 400mg 1 tablet twice daily.

Interventions

Lopinavir / ritonavir

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

Intervention Type: DRUG

2-3N(t)RTI

Intervention Type: DRUG

raltegravir

raltegravir 400mg 1 tablet twice daily.

Intervention Type: DRUG

Eligibility Criteria

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 ≥ 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 (≥7 days apart) HIV RNA results of > 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/µL
• hemoglobin < 7.0 g/dL
• platelet count < 50,000 cells/µL
• ALT > 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 hospitalisation

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kirby Institute

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paddy Mallon

Role: PRINCIPAL_INVESTIGATOR

Mater Misericordiae University Hospital, Dublin

Waldo Belloso

Role: PRINCIPAL_INVESTIGATOR

Hospital Italiano, Argentina

Samuel Ferret

Role: PRINCIPAL_INVESTIGATOR

Hopital Saint-Louis, France

Praphan Phanuphak

Role: PRINCIPAL_INVESTIGATOR

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

Jennifer Hoy

Role: PRINCIPAL_INVESTIGATOR

The Alfred

Locations

CEADI

Buenos Aires, , Argentina

YRGCare Medical Centre

Chennai, , India

University of Malaya Medical Centre

Kuala Lumpur, , Malaysia

JOSHA Research

Bloemfontein, , South Africa

Desmond Tutu HIV Foundation

Cape Town, , South Africa

Chris Hani Baragwanath Hospital

Soweto, , South Africa

HIV-NAT Program on AIDS - Thai Red Cross

Bangkok, , Thailand

Countries

Argentina; India; Malaysia; South Africa; Thailand

References

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.

Reference Type: RESULT

PMID: 23921615 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24204757 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27815068 (View on PubMed)

Other Identifiers

2L body comp sub-study

Identifier Type: -

Identifier Source: org_study_id