Quality of Life and Changes in Metabolism of Lipids and Glucose After Switching to a Nevirapine-based Regimen in HIV+ Patients

Study Overview
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Brief Summary
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The purpose of this trial is to compare the effect of switching to nevirapine (Viramune®)-containing regimen on quality of life of patients with fat abnormalities and virological control whilst receiving a PI-based regimen.

Detailed Description
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Patients will receive one of the current standard of care regimens for the treatment of HIV infection, i.e. nevirapine (Viramune®) must be administered in conjunction with 2NRTIs, as prescribed by the investigator at the study sites. Patients randomized to the nevirapine (Viramune®)-arm of the study will receive 1x200mg tablet once daily for the first 14 days (lead in period) and 1x200 mg tablet twice daily at appropriately spaced intervals subsequently, plus their SOC combination of 2NRTIs as prescribed by the investigators (without changing their prior NRTIs). Patients randomized to continue their standard treatment will receive it as prescribed by the investigators. No dose modification of the study drugs is permitted during the trial. The study drug will be dispensed at randomization and every four weeks thereafter until completion of 48 weeks. After 6 months at least of treatment the switch from PI regimen to NVP regimen will be allowed to all patients included in the PI arm according to patient's willingness. In these patients AST and ALT should be checked at time 0 (switch) and every 2 weeks for 2 months. Study Hypothesis: Between treatment comparison of Nevirapine-based regimen versus PI-based regimen will be based on a null hypothesis of no treatment difference. The null hypothesis will be no difference between the two arms at week 24 (month 6th), against the alternative hypothesis that the mean change in physical domain of the QoL will be 10 points score (SD=20) and the difference between triglycerides normalized patients will be 20%. Comparison(s): The primary analysis on physical domain of QoL will be performed on the changes between last observation carried forward following the LCOF approach (i.e. visit 6 or in case of premature discontinuation visit 5 or 4) and baseline (visit 2) value using fixed-effects ANCOVA model with center and treatment groups as factors and baseline value and MMA type interaction will be also included in the main model.

Official Title
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An Open, Randomised, Multicentre, Comparative Trial, to Evaluate the Benefit of Switching From a PI-based Regimen to a Nevirapine-based Regimen on the Quality of Life, Patient Adherence, Patient's Perception of Fat Redistribution and Metabolic Changes, in HIV+ Patients Suffering From Fat Abnormalities

Conditions
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HIV Infections, Quality of Life

Intervention / Treatment
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* Drug: Nevirapine


Participation Criteria
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Eligibility Criteria
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Main Inclusion criteria: Subject suffering with clinically evident fat redistribution including the lipodystrophic syndrome and/or with abnormal values of triglycerides, cholesterol and/or insulin resistance Subject on treatment with HAART including PIs for at least 9 months, without therapeutic changes for at least 6 months Baseline CD4+ >200 cells/mm3 HIV-1 RNA levels <200 copies/mL at baseline and during the previous 6 months Main Exclusion criteria: Subject with other serious or chronic disease unrelated to HIV Subject with active invasive infections Subject with Karnofsky score less than 50 Prior NNRTs experience Documented or suspected acute hepatitis within 30 days prior to baseline visit, irrespective of AST and ALT values that are >5 ULN Subject receiving hypolipidemic and/or antidiabetic drugs at study entry Subjects with central nervous system disease or pre-existing mental disturbance Subjects on methadone chronic treatment at study entry

Ages Eligible for Study
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Minimum Age: 18 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Nevirapine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life (WHOQoL questionnaire) |  | up to 48 weeks | 
| Change in triglycerides in plasma |  | up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients perception of fat redistribution |  | up to 48 weeks | 
| Adherence to therapy |  | up to 48 weeks | 
| Changes in metabolism of lipids and glucose |  | up to 48 weeks | 
| Bone mineral loss |  | up to 48 weeks | 
| Therapeutic drug levels of antiretrovirals (drug plasma level / IC90) |  | up to 48 weeks | 
| Concentration of antiretrovirals in semen and vaginal secretions |  | up to 48 weeks | 
| Viral load |  | up to 48 weeks | 
| Immunological status |  | up to 48 weeks | 
| Incidence and intensity of clinical and adverse events |  | up to 48 weeks |