Effectiveness of Zidovudine vs. Zidovudine Plus Alpha Interferon vs. Interferon for Treatment of HIV
This study will compare the effectiveness of zidovudine (AZT) alone vs. zidovudine plus interferon (IFN) vs. interferon alone in reducing HIV viral load, lessening immune system deterioration, and increasing the time to development of the first opportunistic infection in HIV-infected patients.
HIV-infected persons 18 years of age and older with a T4 lymphocyte count of 500/mm3 or more and no current opportunistic infections may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood tests, chest X-ray, electrocardiogram, urinalysis, and, for patients with Kaposi s sarcoma lesions, measurement, photographs, and biopsy of lesions.
Patients will be assigned to receive treatment with either zidovudine alone, zidovudine plus interferon or interferon alone. They will continue treatment until one of the following occurs:
- Unacceptable side effects, despite dose modifications
- Development of an opportunistic infection
- Decrease in CD4 count by 20 percent or to an absolute count of less than 200/mm3
- Rapid progression of Kaposi s sarcoma lesions, requiring alternative therapy
- A decision is made to terminate the study
Patients will be followed long term for viral load, immune function, development of opportunistic infections, disease progression, and survival.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Phase III Study With Long-Term Follow-Up of Zidovudine Versus Zidovudine and Alpha-Interferon Versus Alpha-Interferon in Patients With Early HIV Infection|
- Evaluate the relative efficacy of zidovudine (AZT) vs. AZT + alpha interferon (IFN) vs. IFN in increasing time to first opportunistic infection, reducing HIV viremia, and lessening immune system deterioration in HIV-infected persons.
- Patient will remain in long-term follow-up to provide information about the long-term outcomes of receiving anti-HIV treatment, and to provide information on long-term consequences of therapy analogous to a longitudinal natural history study.
|Study Start Date:||September 1988|
|Estimated Study Completion Date:||December 2025|
|Estimated Primary Completion Date:||December 2025 (Final data collection date for primary outcome measure)|
Drug: Ziodovudine and Alpha Interferon
Initial Study: Three Arm (Interventional) Study
This phase III study will evaluate the relative efficacy of zidovudine (AZT) vs. AZT + alpha interferon (IFN) vs. IFN in increasing time to first opportunistic infection, reducing HIV viremia, and lessening immune system deterioration in HIV-infected persons. For the AZT-alone arm, AZT dosing will be the standard regimen of 200 mg q4h. Persons on the AZT + IFN combination arm will receive AZT 100 mg q4h with IFN beginning at 1 million units qd, escalating up to 2.5 million units at 2 weeks, then in increments of 2.5 million units every 2 weeks. Patients on the IFN-alone arm will begin therapy at 5 million units qd and escalate in 2.5 million unit increments every 2 weeks, unless escalations are precluded by toxicity. Patients who have evidence of HIV infection and CD4 count greater than or equal to 500 will be randomized to one of the three treatment groups. Patients will continue to be treated with their assigned medication until intolerable toxicity, opportunistic infection, or progressive Kaposi's sarcoma develops, or CD4 count declines to less than 200/mm(3).
Long-Term Follow-up: Extension Phase (Natural History Study)
This protocol was initiated in 1988 and was the first study to evaluate early intervention with antiretroviral agents in patients with HIV infection. Our statistically significant findings during this pre-HAART era showed that interferon-alpha decreased HIV RNA viral load levels, both alone and in combination with AZT. Research medication has not been administered since January of 1997, but this cohort still serves as an important source of data regarding the long-term medical course of patients who have received an early intervention for HIV infection. Participants will remain in long-term follow-up in order to provide valuable information regarding the long-term outcomes of patients receiving anti-HIV treatment, and to provide information on the long-term consequences of therapy. Hence, this study is analogous to a longitudinal natural history study.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Mary E Wright, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|