To assess the safety and toxicity of zidovudine (AZT)/didanosine (ddI) versus AZT/ddI combined with nevirapine in HIV-infected patients, and to obtain preliminary anti-HIV activity data using immunologic and virologic markers. Previous in vitro studies suggest that HIV that has already developed resistance to AZT and ddI is less able to develop resistance to nevirapine, a non-nucleoside reverse transcriptase inhibitor. Thus, convergent combination therapy with these three drugs in HIV-infected patients may prove more effective.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Nevirapine  Drug: Zidovudine  Drug: Didanosine	Phase II

Further Study Details: 

Expected Total Enrollment:  400

Previous in vitro studies suggest that HIV that has already developed resistance to AZT and ddI is less able to develop resistance to nevirapine, a non-nucleoside reverse transcriptase inhibitor. Thus, convergent combination therapy with these three drugs in HIV-infected patients may prove more effective.

Patients are randomized to receive AZT/ddI plus either nevirapine or placebo daily for 48 weeks, with possible extension for at least 12 weeks. At eight participating sites, ACTG 808 and 809 will be conducted as virologic and pharmacokinetic substudies.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Required:

• PCP prophylaxis for patients with CD4 count < 200 cells/mm3 or a prior history of PCP.

Allowed:

• Trimethoprim with sulfamethoxazole or dapsone, intravenous pentamidine, atovaquone, primaquine-clindamycin or trimetrexate for acute PCP.
• Topical antifungals, clotrimazole, ketoconazole, fluconazole, and amphotericin B for treatment of mucosal and esophageal candidiasis.
• Prophylaxis or therapy for opportunistic infections, as indicated, with other medications such as itraconazole, isoniazid, pyrazinamide, clofazimine, clarithromycin, azithromycin, ethambutol, amikacin, ciprofloxacin, ofloxacin, pyrimethamine, sulfadiazine, and clindamycin.
• Maintenance therapy for opportunistic infections as long as patients have been on a stable dosage regimen for 1 month prior to study entry.
• Ganciclovir for CMV retinitis or gastrointestinal disease as long as patients have been on a stable dose for at least 1 month prior to study entry with no grade 3 or 4 neutropenia or dependence on G-CSF.
• Acyclovir (<= 1000 mg/day) for maintenance of herpes simplex virus infections.
• Erythropoietin or G-CSF if clinically indicated.
• Antibiotics for bacterial infections unless specifically excluded.
• Rifampin or rifabutin.
• Symptomatic treatments such as antipyretics, analgesics, and antiemetics.

Concurrent Treatment: Allowed:

• Local radiation therapy.

Prior Medication: Required:

• At least 6 months of prior cumulative nucleoside therapy with AZT, ddI, or ddC, given as monotherapy or in combination.

Patients must have:

• Prior or current documentation of HIV seropositivity by ELISA confirmed by Western blot, positive HIV antigen, or positive HIV culture, or a second antibody test by a method other than ELISA.
• CD4 count <= 350 cells/mm3.
• Prior cumulative nucleoside therapy of >= 6 months.
• Consent of parent or guardian if less than 18 years of age.

Exclusion Criteria

Concurrent Medication: Excluded:

• Antiretroviral therapies other than study medications.
• Systemic corticosteroids given consecutively for > 21 days.
• Induction or maintenance with foscarnet.
• Systemic cytotoxic chemotherapy for a malignancy.
• Erythromycin.
• Coumadin/warfarin.
• Phenytoin or phenobarbital.
• Amoxicillin/clavulanate acid (Augmentin) or ticarcillin/clavulanate acid (Timentin).

Patients with the following prior conditions are excluded:

• History of pancreatitis.
• History of intolerance to 500 or 600 mg/day AZT or to 400 mg/day ddI tablets or 500 mg/day ddI sachets.
• History of grade 2 or worse peripheral neuropathy.

Prior Medication: Excluded at any time: Prior non-nucleoside reverse transcriptase inhibitors (NVP; L697,611; TIBO; atevirdine).

Excluded within 14 days prior to study entry:

• Acute treatment for a serious infection or any opportunistic infection.
• Biologic response modifiers such as interferon and IL-2.
• Erythromycin.
• Coumadin/warfarin.
• Phenytoin or phenobarbital.
• Ticarcillin/clavulanate acid (Timentin) or amoxicillin/clavulanate acid (Augmentin).

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  United States
      San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
      San Francisco AIDS Clinic / San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
      Summitt Med Ctr / San Francisco Gen Hosp, Oakland,  California,  94609,  United States
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States
      Highland Gen Hosp / San Francisco Gen Hosp, Oakland,  California,  946021018,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
      Rush Presbyterian - Saint Luke's Med Ctr, Chicago,  Illinois,  60612,  United States
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
Iowa
      Univ of Iowa Hosp and Clinic, Iowa City,  Iowa,  52242,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
      Beth Israel Deaconess Med Ctr, Boston,  Massachusetts,  02215,  United States
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States
      Boston Med Ctr, Boston,  Massachusetts,  02118,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States
      St Paul Ramsey Med Ctr, St. Paul,  Minnesota,  55101,  United States
      Hennepin County Med Clinic, Minneapolis,  Minnesota,  55415,  United States
Nebraska
      Univ of Nebraska Med Ctr, Omaha,  Nebraska,  681985130,  United States
New York
      Montefiore Drug Treatment Ctr / Bronx Municipal Hosp, Bronx,  New York,  10461,  United States
      Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx,  New York,  10461,  United States
      Samaritan Village Inc / Bronx Municipal Hosp, Bronx,  New York,  10461,  United States
      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  United States
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States
      Jack Weiler Hosp / Bronx Municipal Hosp, Bronx,  New York,  10465,  United States
      Cornell Univ Med Ctr, New York,  New York,  10021,  United States
      Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx,  New York,  10461,  United States
      Montefiore Med Ctr / Bronx Municipal Hosp, Bronx,  New York,  10467,  United States
      Beth Israel Med Ctr, New York,  New York,  10003,  United States
      City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst,  New York,  11373,  United States
      Saint Clare's Hosp and Health Ctr, New York,  New York,  10019,  United States
      North Central Bronx Hosp / Bronx Municipal Hosp, Bronx,  New York,  10467,  United States
      Comprehensive Health Care Ctr / Bronx Municipal Hosp, Bronx,  New York,  10461,  United States
North Carolina
      Carolinas Med Ctr, Charlotte,  North Carolina,  28203,  United States
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
      Moses H Cone Memorial Hosp, Greensboro,  North Carolina,  27401,  United States
      Wake County Dept of Health, Raleigh,  North Carolina,  27610,  United States
Ohio
      Univ of Cincinnati, Cincinnati,  Ohio,  452670405,  United States
Pennsylvania
      Univ of Pennsylvania at Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Thomas Jefferson Univ Hosp, Philadelphia,  Pennsylvania,  191075098,  United States
      Girard Med Ctr, Philadelphia,  Pennsylvania,  191046073,  United States

Study chairs or principal investigators

D'Aquila R,  Study Chair
Hirsch M,  Study Chair

Study ID Numbers:  ACTG 241
Record last reviewed:  December 1994
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000770
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08