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

Study Overview
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Brief Summary
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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).

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

Conditions
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HIV

Intervention / Treatment
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* Drug: Lopinavir / ritonavir
* Drug: 2-3N(t)RTI
* Drug: raltegravir


Participation Criteria
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Eligibility Criteria
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Second-Line main study identifier: NCT00931463 Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1. Lopinavir / ritonavir + 2-3N(t)RTI<br>LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily + 2-3N(t)RTI | Drug: Lopinavir / ritonavir<br>* LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily<br>Drug: 2-3N(t)RTI<br> <br> |
| Active Comparator: Arm 2. Lopinavir /ritonavir + raltegravir<br> | Drug: Lopinavir / ritonavir<br>* LPV/r 200mg/50mg 4 tabs once daily or 2 tabs twice daily<br>Drug: raltegravir<br>* raltegravir 400mg 1 tablet twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |