The Safety and Effectiveness of Nevirapine and Zidovudine, Given Separately and Together, in HIV-1 Infected Patients Who Have No Symptoms of the Disease

A Multi-Center, Placebo-Controlled, Double-Blind, Randomized Trial Comparing the Activity, Safety, and Tolerance of 1) 400 Mg Nevirapine in Combination With 500-600 Mg Zidovudine Versus Zidovudine Alone in Asymptomatic HIV-1 Infected Patients With 3-24 Months of Prior Zidovudine Therapy and 200-500 CD4 Cells/mm3 and 2) 400 Mg Nevirapine Versus Nevirapine Placebo in Asymptomatic HIV-1 Nucleoside Naive Patients With 200-500 CD4 Cells/mm3

PRIMARY: To compare the effect of nevirapine versus placebo alone or in combination with zidovudine (AZT) on CD4 T-cell count and percentage after 3 and 6 months of treatment. To evaluate the safety and tolerance of nevirapine alone or in combination with AZT.

SECONDARY: To compare the effects of the various treatment combinations on virologic and immunologic markers.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Nevirapine; Drug: Zidovudine

Detailed Description

In Part I, patients who have had prior AZT therapy receive either nevirapine or placebo in combination with AZT. In Part II, patients who are nucleoside naive receive either nevirapine or matching placebo. After 6 months, patients receive open-label nevirapine.

• Study Type: Interventional
• Enrollment: 250
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • UCSD Treatment Ctr
    • San Francisco, California, United States, 94109
      • Saint Francis Mem Hosp
  • Delaware
    • Wilmington, Delaware, United States, 19801
      • Wilmington Hosp
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Community Research Initiative of South Florida
    • Maitland, Florida, United States, 32751
      • Goodgame Med Group
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Univ of Kansas School of Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 405360084
      • Chandler Med Ctr
  • Missouri
    • Kansas City, Missouri, United States, 641082792
      • Kansas City AIDS Research Consortium
  • New York
    • New York, New York, United States, 10001
      • Community Research Initiative on AIDS
  • Ohio
    • Toledo, Ohio, United States, 43699
      • Med College of Ohio
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74114
      • Associates Med and Mental Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Dr Alfred F Burnside Jr
  • Texas
    • Dallas, Texas, United States, 75219
      • Nelson-Tebedo Community Clinic
    • Houston, Texas, United States, 77006
      • Houston Clinical Research Network
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Univ of Utah School of Medicine
  • Virginia
    • Annandale, Virginia, United States, 22203
      • Infectious Disease Physicians Inc
    • Richmond, Virginia, United States, 23219
      • Richmond AIDS Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

• PCP prophylaxis (trimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine), at the discretion of the investigator.
• Antifungal prophylaxis with oral fluconazole or ketoconazole.
• Antiviral prophylaxis for herpes simplex virus with <= 1000 mg/day oral acyclovir.
• Dilantin for prevention and treatment of seizures.

Patients must have:

• Asymptomatic HIV-1 infection, with positive serum antibody to HIV-1 as determined by ELISA or Western blot.
• CD4 count 200-500 cells/mm3 within 4-28 days prior to study entry.
• No conditions indicative of AIDS.
• None of the constitutional symptoms that are specifically excluded.
• Prior AZT for 3-24 months (amended 04/04/94) immediately prior to study entry (Part I) OR no prior AZT (Part II).
• Consent of parent or guardian if less than 18 years of age.

NOTE:

• Co-enrollment in a protocol involving another investigational drug or biologic is not permitted.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Malignancy other than limited cutaneous basal cell carcinoma.
• Psychiatric condition sufficient to impair compliance with protocol requirements.

Concurrent Medication:

Excluded:

• Investigational drugs other than study drugs.
• Systemic glucocorticoids and steroid hormones.
• Dicumarol, warfarin, and other anticoagulant medications.
• Cimetidine.
• Tolbutamide.
• Doxycycline.
• Chloramphenicol.
• Phenobarbital and other barbiturates.
• Foscarnet.
• Erythromycin.
• Amoxicillin-clavulanate (Augmentin).
• Ticarcillin clavulanate (Timentin).
• Biologic response modifiers (alpha interferon, IL-2, immune modulators).

Patients with the following condition are excluded:

History of other clinically important disease (i.e., one that precludes participation in the study).

Prior Medication:

Excluded:

• Antiretroviral medications other than AZT.

Excluded within 4 weeks prior to study entry:

• Immunosuppressive or cytotoxic drugs or other experimental drugs.
• Systemic glucocorticoids and steroid hormones.
• Dicumarol, warfarin, and other anticoagulant medications.
• Cimetidine.
• Tolbutamide.
• Doxycycline.
• Chloramphenicol.
• Phenobarbital and other barbiturates.
• Foscarnet.
• Erythromycin.
• Amoxicillin-clavulanate (Augmentin).
• Ticarcillin clavulanate (Timentin).
• Biologic response modifiers (alpha interferon, IL-2, immune modulators).

Required (for patients in Part I):

• Prior AZT at 500-600 mg daily for at least 3 months but not more than 24 months immediately prior to study entry.

Chronic use of alcohol or drugs sufficient to impair compliance with protocol requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: Double

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Pollard R . Surrogate marker response to NVP/ZDV or ZDV in a blinded clinical trial: correlation to changes in HIV isolate phenotypic susceptibility to NVP and ZDV. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:113

Study record dates

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: August 1, 2002

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Nevirapine; AIDS-Related Complex; Zidovudine
• 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; Antimetabolites; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Nevirapine; Zidovudine
• Other Study ID Numbers: 200C; 1038