Effectiveness of Zidovudine vs. Zidovudine Plus Alpha Interferon vs. Interferon for Treatment of HIV

Initial Study: THREE ARM (INTERVENTIONAL) STUDY This randomized, controlled phase III protocol, initiated in 1988, was the first study to examine intervention with antiretroviral therapy and alpha interferon in patients with HIV infection. It evaluated 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 consisted of the standard regimen of 200 mg q4h. Persons on the AZT + IFN combination arm received 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 began therapy at 5 million units qd and escalated in 2.5 million unit increments every 2 weeks, unless escalations were precluded by toxicity. Patients who had evidence of HIV infection and a CD4 countgreater than or equal to 500 were randomized to one of the three treatment groups. Patients were treated with their assigned medication until intolerable toxicity, opportunistic infection, or progressive Kaposi's sarcoma developed, or CD4 count declined to less than 200/mm(3). Our statistically significant findings during this pre-HAART era study showed that interferon-alpha decreased HIV RNA viral load levels, both alone and in combination with AZT. Long-Term Follow-up: EXTENSION PHASE (NATURAL HISTORY STUDY) Once the intervention phase was completed, this protocol entered a long-term follow-up phase and evolved into a longitudinal natural history study. As of 2013, this work earned the distinction of following a cohort for 25 years or more. It continues to serve as an important source of data regarding the long-term outcomes of patients receiving anti-HIV treatment, and to provide information on the long-term consequences of therapy. In addition, stored blood and cells enable the study of cutting edge research questions, such as those related to immune activation, with new state-of-the-art laboratory assays.