Including IFN-alpha into STI - Settings of ART in Early Chronic HIV-Infection.

Prof. Dr. Norbert H. Brockmeyer, Department of Dermatology, Ruhr-University Bochum, Gudrunstrasse 56, D-44791 Bochum (Germany).

Background: In the course of HIV-infection, the role of interferon (IFN)-alpha seems to be rather paradoxical. It is possible to consider it either as a therapeutic agent or as a major contributor to pathological circumstances associated with AIDS/HIV. As preliminary results of IFN-alpha treatment in early chronic HIV-disease were promising, concepts are considered to integrate IFN-alpha into settings of structured therapy interruptions (STI´s) of ART. Material and Methods: Two study designs are presented, which will be performed in co-operation with the German Competence Network HIV/AIDS. Preliminary results were shown, and the results of a pilot trial will be discussed. Results: In an ongoing controlled study 32 HIV-positive patients with 300 to 500 CD4 lymphocytes responding to ART with plasma viremia < 50 copies of HIV-RNA for at least 6 months before study inclusion will be randomised a) to continue treatment (control group), b) to alternate ART and STI in a two weeks interval, c) to receive PegIFN-alfa2b (PegIntron) in a dosage of 1,5 mcg/kg/week during the STI-intervals or d) to receive PegIFN-alfa2b during ART and during STI´s. After week 20 arms b-d) will be monitored under a prolonged period of STI until viral load exceeds 5000 copies/ml. Preliminary results will be discussed. In a pilot trial 10 treatment-naïve HIV-positive patients (CDC/WHO A and B) were enrolled in two study arms (treatment group n=5; control group n=5). Patients in the treatment group received 80 mcg PegIFN-alfa2b s.c. per week for 6 months. The medium number of CD4 cells in the treatment group rose from 462/mcl (SD=199) to 611/mcl (SD=239) versus 535/mcl (SD=226) to 450/mcl (SD=245), respectively, in the control group. The difference was highly significant with p<0.001. Furthermore, the median number of plasma HIV-RNA copies in the treatment group declined from 22.158 copies/ml (SD=14.295) to 3039 copies/ml (SD=2560) versus 7136 copies/ml (SD=6250) to 40.092 copies/ml (SD=52.075) in the control group. The difference of plasma HIV-RNA decrease after 24 weeks is significant between the two arms with p<0.05. Conclusion: As from these results the application of PegIFN-alfa2b is expected to be beneficial in patients with early chronic HIV-disease, an open randomized phase III study will be conducted within a setting of CD4-monitored STI of ART, where patients are randomized to receive either 80 mcg of PegIFN-alfa2b per week or no treatment during STI.