Clinical trial NCT00415090: Study to Evaluate the Replacement of Reverse Transcriptase Nucleoside/Nucleotide Inhibitors by Nevirapine in Patients on Triple Treatment With Analogues Only
Official title: Substitution by Nevirapine in HIV-1 Infected Patients on Triple Treatment of Reverse Transcriptase Nucleoside/Nucleotide Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: Nevirapine
Antiretroviral treatment
Triple nucleoside therapy
HIV
Treatment Experienced
Lead sponsor: Hospital de Calella
Sponsor class: OTHER
First posted: 2006-12-22
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients with plasma viral load below 50 copies/mL .
timeFrame: after 48 weeks of follow-up
Secondary outcomes:
measure: Time to the appearance of viral load >50 copies/mL in both branches (two consecutive determinations with 4-week separation between both).
timeFrame: During the 48 weeks of follow-up.
measure: Evolution of the CD4 lymphocyte count at 48 weeks.
timeFrame: during 48 weeks of follow-up
measure: Pattern of mutations associated with resistance in patients presenting virological failure.
timeFrame: When there is a virological failure
measure: Incidence of adverse clinical effects and laboratory alterations, giving rise or not to the withdrawal of the investigational treatment.
timeFrame: during the 48 weeks of follow-up
measure: Incidence of AIDS-defining events (CDC C events, 1993).
timeFrame: during the 48 weeks of follow-up
measure: Mortality by any cause.
timeFrame: during the 48 weeks of follow-up
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital.Universitari Germans Trias i Pujol
state: Barcelona
city: Granollers
country: Spain
facility: Hospital General de Granollers
state: Barcelona
city: Granollers
country: Spain
facility: Centre Penitenciari Quatre Camins
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: Hospital de Bellvitge
state: Barcelona
city: Terrassa
country: Spain
facility: Mutua de Terrassa
state: Barcelona
city: Tenerife
country: Spain
facility: Hospital La Candelaria
state: Canarias
city: Reus
country: Spain
facility: Hospital Universitari Sant Joan de Reus
state: Tarragona
city: Barcelona
country: Spain
facility: Centre Penitenciari Brians
city: Barcelona
country: Spain
facility: Hopsital de Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital Sant Jaume de Calella
city: Barcelona
country: Spain
facility: Centre Penitenciari Homes
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos de Madrid
city: Tortosa
country: Spain
facility: Hospital de Tortosa
city: Valencia
country: Spain
facility: Hospital La Fe de Valencia
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
Study officials:
affiliation: Hospital Sant Jaume de Calella
name: Josep Mª Llibre, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: