HIV-1 dynamics in vivo after administration of pegylated interferon- alpha -2b (PEG-intron)

Within a phase I study, the dynamics of HIV-1 during PEG-intron treatment were investigated. Patients eligible for HAART (HIV-RNA > 5000 copies/ml, CD4 greater than or equal to 200/mm super(3)) and naive to previous antiretroviral or IFN-a treatment, consented to PEG-intron subcutaneous injections QW for 4 weeks before initiation of HAART. They were enrolled in five dosing schemes (0.5 mu g/kg, 1.0 mu g/kg, 1.5 mu g/kg, 3.0 mu g/kg, 4.5 mu g/kg). Two baseline blood samples as well as samples at days 1, 2, 4, 8, 15, 22 and 29 were taken for HIV-RNA testing using a hypersensitive RT-PCR assay (cut-off 50 copies/ml). The dynamics of HIV-1 were investigated in 19 patients (2, 2, 3, 5, 5 patients, from 0.5, 1.0, 1.5, 3.0, 4.5 mu g/kg groups, respectively) with an HIV-RNA decline > 0.5 log sub(10) and no rebound. A mathematical model proposed by Neumann et al. was used. The observed viral decline was biphasic with a first phase lasting up to days 4-8. The first phase was governed by the antiviral efficacy ( epsilon ) of the treatment and the slower second phase was determined by the death rate of infected cells ( delta ). The mean (SD) epsilon was estimated to be 65.1% (9.6%), 78.8% (12.2%), 79.6% (8.8%) and 80.8% (6.2%) in 0.5-1.0 mu g/kg, 1.5 mu g/kg, 3.0 mu g/kg, 4.5 mu g/kg treatment groups, respectively (P < 0.05). Antiviral efficacy was found to be positively correlated with maximum viral decline (r = -0.53, P = 0.019) and with baseline CD4 (r = 0.60, P = 0.007). The median (25th, 75th) Delta was estimated to be 0.106 day super(-1) (0.030, 0.182) and did not have any consistent association with treatment dose. In conclusion, antiviral efficacy was associated with baseline immunological parameters and with PEG-intron dose at the lower doses with a plateau effect above 1.5 mu g/kg.