To evaluate the efficacy and safety of zidovudine (ZDV) and lymphoblastoid interferon (IFN)-α combination therapy compared with ZDV monotherapy in HIV-infected subjects with CD4+ cell counts between 150 and 500x106/1.
Open, randomized controlled trial with subjects stratified by the Centers for Disease Control and Prevention (CDC) 1986 classification of HIV disease (group 11/111 or IV). The study was amended to a sequential design in February 1992 to allow interim analyses to be conducted.
Outpatient clinics in 45 hospitals in Europe, Australia and Canada.
A total of 402 previously untreated subjects with symptomatic HIV infection (CDC group IV) and CD4+ count 150–500xT06/1 or asymptomatic HIV infection (CDC group 11/111) with CD4+ count 150–350 x 106/l.
ZDV 250 mg twice daily with or without 3 MU subcutaneous injections of lymphoblastoid IFN-α three times per week.
Main outcome measures
Time to development of a study endpoint defined as: progression from CDC group 11/111 to group IV, group IV non-AIDS to AIDS, or group IV AIDS to a second AIDS-defining condition; also CD4+ count to < 50x 106/1 on two occasions at least 1 month apart or HIV-related death irrespective of CDC group on entry.
There was no reduction in the rate of disease progression for patients receiving ZDV plus IFN-α compared with patients receiving ZDV alone. No major differences between the groups were seen for CD4+ counts or percentages, or p24 antigenaemia. In a subset of 70 patients, a similar proportion from both dose groups showed evidence of ZDV resistance after 48 weeks of treatment. More adverse experiences were seen in the ZDV/IFN-a group.
Combination therapy with low dose lymphoblastoid IFN-α and ZDV revealed no clinical benefit compared with ZDV monotherapy.