Study to Evaluate the Replacement of Reverse Transcriptase Nucleoside/Nucleotide Inhibitors by Nevirapine in Patients on Triple Treatment With Analogues Only

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the proportion of patients with viral load of HIV-1 < 50 copies after 48 weeks of follow-up after randomization to change or not to nevirapine.

Detailed Description
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RTNI (reverse transcriptase nucleoside inhibitors) are a regular part of most antiretroviral combinations. The presence of a smaller or greater degree of cross resistance among all RTNI is increasingly better described and acknowledged, whereby the number of salvage regimens that may be built following the appearance of this resistance to these drugs is by no means unlimited. This proactive treatment change in patients on RTNI-based regimens while the viral load is still suppressed would avoid the selective replication period under antiviral pressure following the failure of the regimen in which resistance-associated mutations accumulate. This therapeutic approach has demonstrated its effectiveness in clinical practice, albeit not in this scenario. If we wait until the viral load is detectable there is sufficient evidence that resistance to RTNI will appear and that this resistance will compromise future salvage options. To intensify with this proactive approach these combinations based on N/NNRTI (nucleotide analog), the NNRTI are an optimal alternative.There is vast experience with NVP in simplification/maintenance trials. In direct comparative simplification studies in patients with virological response, the response rates with NVP or EFV have shown no differences. With a relative risk (RR) of virological failure of 0.54 with regard to the continuation of PI (protease inhibitors), NVP is one of the best simplification treatment options in HIV-1-infected patients.

Official Title
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Substitution by Nevirapine in HIV-1 Infected Patients on Triple Treatment of Reverse Transcriptase Nucleoside/Nucleotide Inhibitors

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Nevirapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients on triple treatment with 3 nucleoside analogues or transcriptase nucleotide inhibitors in virological suppression. Age >= 18 years. Confirmed diagnosis of HIV-1 infection. Viral load < 50 copies/ml over the previous six months, including at least two consecutive determinations. Value of ALT transaminase £ 2.5 times the normal value of the laboratory of each centre. Acceptance and signature of the informed consent form. Exclusion Criteria: Pregnant women or those who intend to become pregnant in the study period. Having had an active infection in the previous month. Previous exposure to any reverse transcriptase non-nucleoside inhibitor (nevirapine, efavirenz or delavirdine). Simultaneous treatment with methadone. Patients with serious hepatic dysfunction

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 |
| --- | --- |
| No Intervention: 1<br>Follow with same ARV treatment | |
| Experimental: 2<br>Switch one of ARV drugs to Nevirapine | Drug: Nevirapine<br>* Switch one of ARV drugs to Nevirapine<br>* Other names: Switch one of ARV drugs to Nevirapine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with plasma viral load below 50 copies/mL . |  | after 48 weeks of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the appearance of viral load >50 copies/mL in both branches (two consecutive determinations with 4-week separation between both). |  | During the 48 weeks of follow-up. | 
| Evolution of the CD4 lymphocyte count at 48 weeks. |  | during 48 weeks of follow-up | 
| Pattern of mutations associated with resistance in patients presenting virological failure. |  | When there is a virological failure | 
| Incidence of adverse clinical effects and laboratory alterations, giving rise or not to the withdrawal of the investigational treatment. |  | during the 48 weeks of follow-up | 
| Incidence of AIDS-defining events (CDC C events, 1993). |  | during the 48 weeks of follow-up | 
| Mortality by any cause. |  | during the 48 weeks of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nevirapine, Antiretroviral treatment, Triple nucleoside therapy, HIV, Treatment Experienced