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2NN & CHARM Long-Term Follow-up Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00127972
Recruitment Status : Completed
First Posted : August 9, 2005
Last Update Posted : April 30, 2007
Boehringer Ingelheim
Information provided by:
International Antiviral Therapy Evaluation Center

Brief Summary:
It is desirable to obtain extended follow up data on subjects who participated in the 2NN study and the CHARM study in order to see if the beneficial effect of using nevirapine continues up to 144 weeks of treatment.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: stavudine Drug: lamivudine Drug: nevirapine Drug: efavirenz Drug: trizivir Phase 4

Detailed Description:

The 2NN study has been completed, the first large randomised trial comparing the efficacy and safety of ART containing two nucleoside analogue reverse transcriptase inhibitors (nRTI: d4T+3TC) and either NVP-od, NVP-bd, EFV or the combination of NVP+EFV in the treatment of chronically HIV-1 infected ART naive patients. Data from this randomized study show no significant differences in response to treatment, and virologic and immunologic efficacy in the single NNRTI arms NVP-od, NVP-bd and EFV. This contrasts with previous cohort studies, which showed a relative hazard in virologic or treatment failure of more than two for those starting with NVP compared to those starting with EFV.

Despite the results of the 2NN study, question remains whether the comparability of NVP and EFV is maintained over a longer period of follow-up. Therefore, this study is designed to assess the durability of the efficacy of the regimens used in the 2NN study.

In the initial CHARM study, the effect of adding nevirapine and/or hydrea to a triple NRTI regimen (trizivir i.e. abacavir, lamivudine and zidovudine) in terms of efficacy and tolerability was investigated in anti retroviral naïve patients. The primary endpoint was treatment failure and follow up was 72 weeks. A total of 229 patients were included. The use of hydrea was prematurely stopped because adding hydrea significantly contributed to treatment failure through enhancement of the toxicities associated with its use. Subjects in the nevirapine group reached a plasma HIV-1 RNA level < 50 copies/ml quicker (log rank test p = 0.011). In addition, in an as treated analysis only 16.2% of subjects adding nevirapine versus 39.5% adding no nevirapine reached the primary endpoint (p=0.027). These results resemble the findings in the ACTG A5059 study. The trizivir arm of this ACTG study was stopped, because anti-retroviral naïve subjects randomized to receive trizivir experienced virological failure earlier and more frequent than subjects who were randomized to receive either of the two other treatment regimens being evaluated in that study. The two other treatment regimens were:

  1. a combination of zidovudine plus lamivudine plus efavirenz and
  2. trizivir plus efavirenz.

It is desirable to obtain extended follow up data on subjects who participated in the CHARM study in order to see if the beneficial effect of adding nevirapine to trizivir continues or even increases after 72 weeks of treatment.

In addition to this main objective, another important issue regards the known association between the use of nevirapine and the occurrence of certain untoward effects, including the development of rash, clinical hepatitis and a hypersensitivity syndrome which usually presents with rash, elevated alanine aminotransferase and/or aspartate aminotransferase, eosinophilia and a host of other constitutional symptoms. The possibility that a metabolite of nevirapine might be responsible for one or the other of these events has been evaluated but could not be confirmed. Data is equivocal on whether nevirapine levels themselves are associated with these events, probably because of "noise" in the retrospective analyses that was used. Animal models would suggest, though, that supratherapeutic nevirapine levels are associated with these events. It seems reasonable to assume that there is a sub-population of people at risk for all of these events (especially hypersensitivity) based on their genetic make-up in that it is known that many patients easily tolerate significantly elevated levels of nevirapine while others may get these side effects with relatively normal levels.

To facilitate the safe administration of nevirapine to patients, this study also aims to identify a gene or genes closely associated with these events, and from that a phenotype associated with that genotype which is at increased risk.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 763 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: A Retrospective Study to Compare the 3-Year Antiviral Efficacy of Nevirapine and Efavirenz in Combination With D4t and 3tc in 2NN Patients and of Trizivir Versus Trizivir Plus Nevirapine in CHARM Patients
Study Start Date : February 2004
Actual Study Completion Date : April 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Nevirapine

Primary Outcome Measures :
  1. To determine whether the number of patients with treatment failure after 144 weeks of follow-up is different between study arms

Secondary Outcome Measures :
  1. To determine whether the percentage of patients with treatment failure after 144 weeks of follow-up is different between the treatment arms
  2. To determine whether the percentage of patients with virologic failure after 144 weeks of follow-up is different between the treatment arms

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Participation in the original 2NN or CHARM study

Exclusion Criteria:

  • None

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00127972

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Holdsworth House Medical Practice
Darlinghurst, Australia, NSW2010
Sponsors and Collaborators
International Antiviral Therapy Evaluation Center
Boehringer Ingelheim
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Study Chair: Joep MA Lange, MD PhD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Principal Investigator: Mark Bloch, MD Holdsworth House General Practice
Additional Information:
Layout table for additonal information Identifier: NCT00127972    
Other Study ID Numbers: 04IAT0035
First Posted: August 9, 2005    Key Record Dates
Last Update Posted: April 30, 2007
Last Verified: April 2007
Keywords provided by International Antiviral Therapy Evaluation Center:
Treatment Experienced
Additional relevant MeSH terms:
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HIV Infections
Blood-Borne Infections
Communicable Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers