HIVPhase 4NCT01513122
Bone and Body Comp: A Sub Study of the SECOND-LINE Study
A Phase 4 study testing Lopinavir / ritonavir, 2-3N(t)RTI and raltegravir in people with HIV, run by Kirby Institute at 7 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- HIV
- What is being tested?
- Lopinavir / ritonavir, 2-3N(t)RTI and raltegravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 7 sitesin 5 countries
- Study dates
- Feb 2010to Aug 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
South Africa3 sites
JOSHA Research
Bloemfontein
Desmond Tutu HIV Foundation
Cape Town, 7925
Chris Hani Baragwanath Hospital
Soweto
About this study
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
- Being tested
- Lopinavir / ritonavir, 2-3N(t)RTI, raltegravir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir / ritonavirDrug
LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily
2-3N(t)RTIDrug
raltegravirDrug
raltegravir 400mg 1 tablet twice daily.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Lopinavir / ritonavir; Drug: 2-3N(t)RTI |
| Arm 2. Lopinavir /ritonavir + raltegravir | Active comparator | Not described Receives: Drug: Lopinavir / ritonavir; Drug: raltegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Bone Mineral Density Changes From Baseline to 48 Weeks as Measured by DXA Scan
Measured: 48 weeks
Mean Limbs Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan
Measured: 48 weeks
Secondary outcomes (4)
Mean Total Body Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan
Measured: 48 weeks
Mean Triglycerides Changes From Baseline to 48 Weeks
Measured: 48 weeks
Mean Total Cholesterol Changes From Baseline to 48 Weeks
Measured: 48 weeks
Mean Glucose Changes From Baseline to 48 Weeks
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2012 (estimated)
- Study startFeb 2010
- Primary completionSep 2012
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 210 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kirby Institute
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Paddy Mallon, Principal investigator, Mater Misericordiae University Hospital, DublinWaldo Belloso, Principal investigator, Hospital Italiano, ArgentinaSamuel Ferret, Principal investigator, Hopital Saint-Louis, FrancePraphan Phanuphak, Principal investigator, HIV-NAT Program on AIDS - Thai Red Cross, BangkokJennifer Hoy, Principal investigator, The Alfred
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01513122
- Sponsor's protocol ID
- 2L body comp sub-study
- Status last verified
- Jun 2025
- First submitted
- 16 Jan 2012
- Last updated
- 26 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 23921615Martin 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.
PubMed 24204757Boyd 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.
PubMed 27815068
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bone and Body Comp: A Sub Study of the SECOND-LINE Study
- ClinicalTrials.gov ID
- NCT01513122
- Acronym / sponsor ID
- 2L body comp sub-study
- Conditions
- HIV
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- Kirby InstituteOther government
- Study start
- Feb 2010
- Primary completion
- Sep 2012 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 20 Jan 2012 (estimated)
- Results
- Posted 17 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1. Lopinavir / ritonavir + 2-3N(t)RTI | Active comparator | Drug: Lopinavir / ritonavir, Drug: 2-3N(t)RTILPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3N(t)RTI |
| Arm 2. Lopinavir /ritonavir + raltegravir | Active comparator | Drug: Lopinavir / ritonavir, Drug: raltegravir |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- The following laboratory variables:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lopinavir / ritonavirLPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily | Drug | 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 |
| raltegravirraltegravir 400mg 1 tablet twice daily. | Drug | Arm 2. Lopinavir /ritonavir + raltegravir |
Primary outcome
Mean Bone Mineral Density Changes From Baseline to 48 Weeks as Measured by DXA Scan
Time frame: 48 weeks
Mean Limbs Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan
Time frame: 48 weeks
4 secondary outcomes
Mean Total Body Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan
Time frame: 48 weeks
Mean Triglycerides Changes From Baseline to 48 Weeks
Time frame: 48 weeks
Mean Total Cholesterol Changes From Baseline to 48 Weeks
Time frame: 48 weeks
Mean Glucose Changes From Baseline to 48 Weeks
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23921615Martin 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.
- Results publication: PubMed 24204757Martin 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.
- Derived from this study: PubMed 27815068Boyd 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paddy Mallon principal investigator
Mater Misericordiae University Hospital, Dublin
Waldo Belloso principal investigator
Hospital Italiano, Argentina
Samuel Ferret principal investigator
Hopital Saint-Louis, France
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lopinavir / ritonavir, 2-3N(t)RTI and raltegravir in people with HIV, run by Kirby Institute at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in South Africa, Argentina, India, Malaysia, Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Bone Mineral Density Changes From Baseline to 48 Weeks as Measured by DXA Scan (time frame: 48 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01513122, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2025.