Clinical trial NCT01513122: Bone and Body Comp: A Sub Study of the SECOND-LINE Study
Official title: Bone and Body Comp: A Sub Study of the SECOND-LINE Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Lead sponsor: Kirby Institute
Sponsor class: OTHER_GOV
First posted: 2012-01-20
Enrollment: 210
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Second-Line main study identifier: NCT00931463

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

Primary outcomes:
measure: Mean Bone Mineral Density Changes From Baseline to 48 Weeks as Measured by DXA Scan
timeFrame: 48 weeks
measure: Mean Limbs Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan
timeFrame: 48 weeks
Secondary outcomes:
measure: Mean Total Body Fat Changes From Baseline to 48 Weeks as Measured by DXA Scan
timeFrame: 48 weeks
measure: Mean Triglycerides Changes From Baseline to 48 Weeks
timeFrame: 48 weeks
measure: Mean Total Cholesterol Changes From Baseline to 48 Weeks
timeFrame: 48 weeks
measure: Mean Glucose Changes From Baseline to 48 Weeks
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: CEADI
city: Chennai
country: India
facility: YRGCare Medical Centre
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
city: Bloemfontein
country: South Africa
facility: JOSHA Research
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation
city: Soweto
country: South Africa
facility: Chris Hani Baragwanath Hospital
city: Bangkok
country: Thailand
facility: HIV-NAT Program on AIDS - Thai Red Cross
Study officials:
affiliation: Mater Misericordiae University Hospital, Dublin
name: Paddy Mallon
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Italiano, Argentina
name: Waldo Belloso
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Saint-Louis, France
name: Samuel Ferret
role: PRINCIPAL_INVESTIGATOR
affiliation: HIV-NAT Program on AIDS - Thai Red Cross, Bangkok
name: Praphan Phanuphak
role: PRINCIPAL_INVESTIGATOR
affiliation: The Alfred
name: Jennifer Hoy
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.