Safety and Efficacy of Zidovudine for Asymptomatic HIV-Infected Individuals

Condition(s) targeted: HIV Infections

Intervention: Zidovudine (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Volberding P, Study Chair

To determine if treatment with zidovudine (AZT) will delay or prevent the onset of AIDS or AIDS related complex (ARC) in individuals infected with HIV but who do not have symptoms of AIDS or ARC. Also, to compare the dose of AZT found to be useful in AIDS and severe ARC with a lower dose to see if side effects can be reduced.

Results from several studies show that a high percentage of people infected with HIV will eventually develop AIDS or ARC unless an effective treatment is found. Because AZT is known to prolong survival in patients with AIDS or severe ARC and has acceptable toxicity in advanced disease, it is reasonable to try it in less advanced cases.

Official title: Safety and Efficacy of Zidovudine for Asymptomatic HIV-Infected Individuals

Study design: Treatment, Double-Blind

Detailed description: Results from several studies show that a high percentage of people infected with HIV will eventually develop AIDS or ARC unless an effective treatment is found. Because AZT is known to prolong survival in patients with AIDS or severe ARC and has acceptable toxicity in advanced disease, it is reasonable to try it in less advanced cases.

Patients entered in the study are randomly assigned to one of two doses of AZT or to placebo (inactive medication). Patients take 3 capsules 5 times a day (every 4 hours from 8 am until 12 pm).

The capsules contain either AZT or placebo and are identical in appearance so that neither patient nor physician knows which treatment the patient is receiving. The higher dose corresponds to the dose found to be useful in patients with AIDS or severe ARC. Patients visit the clinic every 2 weeks for the first 16 weeks, then once a month after that for evaluation. Treatment will continue until the results from the study have been analyzed, which could be as long as 3 years. If side effects occur, the dose of study medication will be decreased or temporarily stopped. If the side effects are severe, then study medication will be stopped permanently.

AMENDED: Effective with Version 4 (900226), dosing for ALL patients on Phase 2 study drug, regardless of CD4+ substudy, will proceed as open-label AZT. Original treatment assignments employed in the > 500 cells/mm3 substudy during the period from August 16, 1989 through the release of this new version. Also, toxicity management and dose modification of AZT for patients receiving Phase 2 study drug have been changed.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria

Patients must:

- Be HIV seropositive and asymptomatic.

- Have normal neurologic exam as defined by the Micro Neuro-AIDS assessment.

Concurrent Medication

- Required: Prophylaxis for Pneumocystis carinii pneumonia (PCP). Aerosolized

pentamidine is preferred but if not possible, Trimethoprim / sulfamethoxazole 1 DS

tablet per day or Dapsone 50 - 100 mg per day is allowed.

Exclusion Criteria

- Active drug or alcohol abuse sufficient to prevent adequate compliance with study

therapy in the investigator's opinion.

Co-existing Condition:

Patients with the following diseases or conditions are excluded:

- Hemophilia.

- Oral candida infection documented by morphology or by response to antifungal therapy

within 2 years of study entry.

- Oral hairy leukoplakia at any time prior to study entry.

- Herpes zoster infection (including single dermatome infection) within 2 years of study

entry.

- Active diarrhea as defined by 3 or more liquid stools per day.

- Temperature > 37. 8 degrees C.

- Grade 1 impairment on two or more items (mild AIDS dementia complex) in the ACTG Micro

Neuro-AIDS Assessment.

- Prior history of malignancy other than cutaneous basal cell carcinomas or cervical

carcinoma in situ.

Patients with the following are excluded from entry:

- AIDS or AIDS-related complex defining symptoms.

- Significant, chronic underlying medical illnesses which would impair continuous

participation in this 3-year clinical trial.

- Hemophilia.

Prior Medication: Excluded:

- Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP).

- Other experimental medications.

- Excluded within 60 days of study entry:

- Antiretroviral drugs or immunomodulators (biologic response modifiers).

- Excluded within 120 days of study entry:

- Systemic corticosteroids.

Prior Treatment: Excluded within 3 months of study entry:

- Blood transfusion.

Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States

Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco, California 94115, 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

Palo Alto Veterans Adm Med Ctr / Stanford Univ, Palo Alto, California 94304, United States

UCLA CARE Ctr, Los Angeles, California 90095, United States

Children's Hosp of San Francisco, San Francisco, California 94118, United States

San Francisco AIDS Clinic, San Francisco, California 94143, United States

Stanford Univ School of Medicine, Stanford, California 94305, United States

Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States

Harbor UCLA Med Ctr, Torrance, California 90502, United States

George Washington Univ Med Ctr, Washington, District of Columbia 20037, United States

Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States

Northwestern Univ Med School, Chicago, Illinois 60611, United States

Johns Hopkins Hosp, Baltimore, Maryland 21287, United States

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

Univ of Minnesota, Minneapolis, Minnesota 55455, United States

St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States

SUNY / State Univ of New York, Syracuse, New York 13210, United States

SUNY - Stony Brook, Stony Brook, New York 117948153, United States

Univ of Rochester Medical Center, Rochester, New York 14642, United States

Mem Sloan - Kettering Cancer Ctr, New York, New York 10021, United States

Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, 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

Bronx Veterans Administration / Mount Sinai Hosp, Bronx, New York 10468, United States

SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States

Saint Luke's - Roosevelt Hosp Ctr, New York, New York 10025, United States

Beth Israel Med Ctr / Peter Krueger Clinic, New York, New York 10003, United States

City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst, New York 11373, United States

Duke Univ Med Ctr, Durham, North Carolina 27710, United States

Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States

Columbus Children's Hosp, Columbus, Ohio 432052696, United States

Holmes Hosp / Univ of Cincinnati Med Ctr, Cincinnati, Ohio 452670405, United States

Univ Hosp of Cleveland / Case Western Reserve Univ, Cleveland, Ohio 44106, United States

Univ of Pittsburgh Med School, Pittsburgh, Pennsylvania, United States

Julio Arroyo, West Columbia, South Carolina 29169, United States

Univ of Washington, Seattle, Washington 98105, United States

Click here for more information about Zidovudine

Related publications:

Volberding PA, Lagakos SW, Grimes JM, Stein DS, Balfour HH Jr, Reichman RC, Bartlett JA, Hirsch MS, Phair JP, Mitsuyasu RT, et al. The duration of zidovudine benefit in persons with asymptomatic HIV infection. Prolonged evaluation of protocol 019 of the AIDS Clinical Trials Group. JAMA. 1994 Aug 10;272(6):437-42.

Choi S, Lagakos SW, Schooley RT, Volberding PA. CD4+ lymphocytes are an incomplete surrogate marker for clinical progression in persons with asymptomatic HIV infection taking zidovudine. Ann Intern Med. 1993 May 1;118(9):674-80.

Volberding PA, Lagakos SW, Grimes JM, Stein DS, Rooney J, Meng TC, Fischl MA, Collier AC, Phair JP, Hirsch MS, et al. A comparison of immediate with deferred zidovudine therapy for asymptomatic HIV-infected adults with CD4 cell counts of 500 or more per cubic millimeter. AIDS Clinical Trials Group. N Engl J Med. 1995 Aug 17;333(7):401-7.

Vella S, Giuliano M, Dally LG, Agresti MG, Tomino C, Floridia M, Chiesi A, Fragola V, Moroni M, Piazza M, et al. Long-term follow-up of zidovudine therapy in asymptomatic HIV infection: results of a multicenter cohort study. The Italian Zidovudine Evaluation Group. J Acquir Immune Defic Syndr. 1994 Jan;7(1):31-8.

Volberding PA, Lagakos SW, Koch MA, Pettinelli C, Myers MW, Booth DK, Balfour HH Jr, Reichman RC, Bartlett JA, Hirsch MS, et al. Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. N Engl J Med. 1990 Apr 5;322(14):941-9.

Volberding P. The value of the CD4+ count of 500 cells/microliters. Drugs. 1995;49 Suppl 1:4-8; discussion 38-40. Review.

Lenderking WR, Gelber RD, Cotton DJ, Cole BF, Goldhirsch A, Volberding PA, Testa MA. Evaluation of the quality of life associated with zidovudine treatment in asymptomatic human immunodeficiency virus infection. The AIDS Clinical Trials Group. N Engl J Med. 1994 Mar 17;330(11):738-43.

Wu AW, Rubin HR, Mathews WC, Ware JE Jr, Brysk LT, Hardy WD, Bozzette SA, Spector SA, Richman DD. A health status questionnaire using 30 items from the Medical Outcomes Study. Preliminary validation in persons with early HIV infection. Med Care. 1991 Aug;29(8):786-98.

Jacobson MA, Gundacker H, Hughes M, Fischl M, Volberding P. Zidovudine side effects as reported by black, Hispanic, and white/non-Hispanic patients with early HIV disease: combined analysis of two multicenter placebo-controlled trials. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Jan 1;11(1):45-52.

Last updated: June 23, 2005