An Open-label, Non-randomized, Single-arm Study to Investigate the Mechanism(s) by Which Nevirapine Increases Plasma HDL in HIV+ Subjects

An Open-label, Non-randomized, Single-arm Study, to Investigate the Mechanism(s) by Which Nevirapine Increases Plasma High Density Lipoproteins Concentration in HIV+ Subjects Treated With VIRAMUNE® Tablets

1. In order to obtain further insight as to how NVP affects HDL metabolism, the in vivo kinetics of the HDL apolipoprotein, Apo A-1, before and 6 weeks after initiation of NVP containing treatment were evaluated. In addition, the activity of the key enzymes related to HDL metabolism were assessed.

   [ Designated as safety issue: No ]

2. In order to determine the relevance of the HDL increase in decreasing cardiovascular risk in HIV-positive subjects we evaluated endothelial function (FMD) as a surrogate marker for cardiovascular disease in patients.

[ Designated as safety issue: No ]

Study Overview

• Status: Completed
• Conditions: HIV Infections; Metabolism, Lipids
• Intervention / Treatment: Drug: nevirapine

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • 1100.1426.01 Academic Medical Centre
  • Amsterdam, Netherlands
    • 1100.1426.02 Onze Lieve Vrouwe Gasthuis
• United Kingdom
  • London, United Kingdom
    • 1100.1426.44001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients will be included when they meet the following criteria:

1. 18 years of age or older.
2. Ability and willingness to provide signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation.
3. Patients on stable therapy with Trizivir only (or its equivalent component drugs), for at least 6 months prior to screening.
4. Patients with plasma HIV-1-RNA <=50 copies/mL documented on at least two occasions within 6 months prior to enrollment.
5. Documentation of plasma HIV-1 RNA of <=50 copies/mL for >=6 months while on Trizivir without other antiretroviral agent. Documentation will include dates and results of all viral load testing from the previous six months.
6. Ability and willingness to complete the study.

Exclusion Criteria:

Patients will not be included when they meet one or more of the following criteria:

1. Previous exposure to NNRTI drugs.
2. Documented diabetes mellitus.
3. Documented hypertension (systolic >155 mmHg and/or diastolic >95 mmHg).
4. Fasting hypertriglyceridemia (>5.6 mmol/L or 500 mg/dl).
5. Use of lipid-lowering medication during the 90 days prior to study enrollment.
6. Chronic active hepatitis B and/or C infection by history.
7. Anemia (Hb <7.0 mmol/l or 11 g/dl hematocrit <32%).
8. Active opportunistic infection or neoplasm within 3 months prior to screening visit with the exception of cutaneous Kaposi's sarcoma without evidence of progressive disease.
9. Any history of cardiovascular disease (infarction, heart failure, peripheral vascular disease, cerebrovascular disease).
10. Hepatic, renal or thyroid abnormalities, as determined significant by the Principal Investigator.
11. Pregnancy or lactation.
12. Active anticoagulation therapy (coumarin derivates, heparin).
13. History of HIV-2 infection.
14. Female patients with CD4 counts >250 cells/mm3.
15. Male patients with CD4 counts >400 cells/mm3. Others which can not be listed here.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage change of fractional synthetic rate (FSR) of Apo A-1	after 6 weeks of treatment
Percentage change of flow mediated dilatation (FMD)	after 6 and 24 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage change in the proteins involved in HDL metabolism	after 6 and 24 weeks of treatment
The percentage change in plasma levels of lipoproteins in the fasting lipid panel (TC, LDL, HDL, TG) from Week 0 (baseline) to 6 and 24 weeks of treatment with NVP-based antiretroviral therapy	from week 0 to 6, and 24 weeks of treatment
The percentage change in activity (and/or mass) of the constituents of the lipid enzymes panel from Week 0 to 24 weeks of NVP-based antiretroviral therapy	from week 0 to 24 weeks of treatment

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info
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Study record dates

Study Major Dates

• Study Start: November 1, 2003
• Primary Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: September 2, 2005
• First Submitted That Met QC Criteria: September 2, 2005
• First Posted (Estimate): September 5, 2005

Study Record Updates

• Last Update Posted (Actual): December 28, 2017
• Last Update Submitted That Met QC Criteria: December 27, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Nevirapine
• Other Study ID Numbers: 1100.1426