The Once A Day Protease Inhibitor Regimens

Study Overview
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Brief Summary
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Atazanavir (ATV) and fosamprenavir (fAPV) are new protease inhibitors that can be administered once-a-day and boosted with ritonavir (r). Prior studies have demonstrated that both are effective in treatment of ARV-naïve HIV-infected people. This study was designed to demonstrate if a HAART regimen containing ATV/r is not inferior to a HAART regimen containing fAPV/r, in ARV-naïve patients over a 96-week period. This is a phase IV, single center, randomized, open label, 2-arm clinical trial in ARV therapy-naïve patients with HIV-1 RNA >1,000 copes/mL and CD4 cell count <350 cells/mm3. Patients will be randomized to receive tenofovir and emtricitabine plus either ATV (300mg qd) and ritonavir (100mg qd) or fAPV (1400mg qd) and ritonavir (200mg qd).

Detailed Description
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Over the past decade, there have been significant advances toward fighting the progression of HIV disease. Current treatment strategies consist of utilization of potent combination antiretroviral therapy to suppress HIV replication below detectable limits limiting the potential for the emergence of resistant viruses, boosting CD4 cell counts and thereby delaying disease progression. Treatment of HIV-1 infection with Highly Active Antiretroviral Therapy (HAART) regimens containing a protease inhibitor (PI) and two nucleoside reverse transcriptase inhibitor (NRTIs) has been shown to prolong survival and decrease disease progression. Despite these potent antiretroviral agents, current available therapies continue to fail in some patients. Poor adherence to complex treatment regimens remains a significant cause of suboptimal viral suppression leading to emerge of resistant virus. Atazanavir and fosamprenavir were recently FDA approved protease inhibitors. The efficacy and safety profile of these two drugs have been established in clinical trials enrolling antiretroviral therapy naïve and protease inhibitor experienced patients. Atazanavir and fosamprenavir are the only protease inhibitors approved for a once a day regimen and this may set a new standard for treatment of antiretroviral therapy naïve HIV infected patients. Adherence to the medicines, a key component of treatment success, could be significantly improved by using these once daily regimens. However, no head-to-head trials comparing the safety and efficacy of fosamprenavir and atazanavir have been published. This prospective, randomized, open label 2-arm study will compare these two protease inhibitors for therapy of antiretroviral treatment-naïve HIV-infected patients. Patients who are successfully screened for eligibility will be randomized to receive tenofovir and emtricitabine plus either atazanavir (300mg qd) and ritonavir (100mg qd) or fosamprenavir (1400mg qd) and ritonavir (200mg qd). Participants will undergo assessment on day 1 and attend study visits at weeks 6, 12 and every 3 months until the completion of the study on week 96. Antiretroviral Medication Self-Report and 3-Day HIV Medication Self-Report questionnaires will be applied at weeks 6, 12 and every 3 month, thereafter, until week 96. Changes in Body Appearance questionnaire will be applied at baseline and weeks 24, 48, 72, and 96.

Official Title
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PIQD: The Once a Day Protease Inhibitor Regimens. Ritonavir Boosted Atazanavir vs. Ritonavir Boosted Fosamprenavir Used in Combination With Tenofovir and Emtricitabine in HIV-1 Infected Antiretroviral Treatment-Naïve Patients.

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: ritonavir-boosted atazanavir
* Drug: ritonavir-boosted fosamprenavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older. Patient agrees to participate in the study by giving written informed consent. Documentation of HIV infection. No prior treatment with any anti-retroviral agent. CD4 cell count < 350 cells x mm3 or with an AIDS defining condition. Viral load > 1,000 copies/mL Exclusion Criteria: Less than 18 years old. Current pregnancy or breastfeeding. Any previous antiretroviral regimen. Severe hepatic impairment that precludes the use of either study drug. This will be defined as any laboratory value of Grade 3 or 4 on the ACTG scale. Use of any contra-indicated medication as defined in the package insert for each drug. Any condition that, in the judgment of the investigator, precludes successful participation in the study.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atazanavir oral once daily<br>HIV treatment | Drug: ritonavir-boosted atazanavir<br>* 100 mg ritonavir plus 300 mg atazanavir in combination with tenofovir-emtricitabine fixed dose combination given once daily.<br>* Other names: Reyataz plus Norvir;|
| Active Comparator: Fosamprenavir oral once daily<br>HIV treatment | Drug: ritonavir-boosted fosamprenavir<br>* 100 mg ritonavir plus 1,400 mg fosamprenavir in combination with tenofovir-emtricitabine fixed dose combination given once daily.<br>* Other names: Lexiva plus Norvir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patient With Viral Load Less Than 400 Copies/mL |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4 Cell Count Change From Baseline During Treatment. |  | 24 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1 infected people, Antiretroviral treatment-naïve, Atazanavir, Fosamprenavir, ARV Treatment Naive