Pharmacodynamics of PEG-IFN-α-2a in HIV/HCV co-infected patients: Implications for treatment outcomes

Abstract

Background & Aims-The pharmacokinetics and pharmacodynamics of pegylated-interferon-α-2a (PEG-IFN) have not been described in HCV/HIV co-infected patients. We sought to estimate the pharmacokinetics and pharmacodynamics of PEG-IFN and determine whether these parameters predict treatment outcome.

Hepatitis C virus viral kinetics during α-2a or α-2b pegylated interferon plus ribavirin therapy in liver transplant recipients with different immunosuppression regimes

“…35 In contrast, in our LT patients, the only potential correlate with ETVR was viral decline at week 12, probably because delayed declines, as seen before in some non-immunosuppressed 24,[36][37][38][39] and in HIV/HCV coinfected patients. 13,27,29,33 Finally, we found no significant influence of donor/recipient IL28B rs12979860 allele combinations, although the small number of patients analysed may preclude confirming the significant associations found in other studies. 40,41 The fact that treatment efficacies during the first few days of treatment were significantly lower (0-26%) than those reported in immunocompetent patients is consistent with previous observations on other monoinfected 30,37 and, especially, on HIV-coinfected individuals.…”

“…9,[44][45][46][47][48][49][50] More than half of our CsA patients showed delayed monophasic viral load kinetics, which did not preclude SVR, as seen in some HCV/HIV coinfected patients with delayed monophasic declines. 27,33 Our results are surprising in the sense that a faster decline may be expected under CsA due to its suppressive effect on HCV replication demonstrated in cell culture, animal models, or in clinical trials. 9,[44][45][46] We hypothesize that, in some patients, CsA immunosuppression may initially override the inhibitory effects on viral replication during the first weeks of therapy.…”

“…40,41 The fact that treatment efficacies during the first few days of treatment were significantly lower (0-26%) than those reported in immunocompetent patients is consistent with previous observations on other monoinfected 30,37 and, especially, on HIV-coinfected individuals. 33,34,42,43 The low efficacy found in our 3 immunocompetent controls (20-22%) may also indicate a role for drug levels and pharmacokinetics. 14,43 In some of our LT patients, virus half-life during the first phase decline appears longer than that published for non-immunosuppressed individuals, but consistent with the range observed (1.…”

“…33,34,42,43 The low efficacy found in our 3 immunocompetent controls (20-22%) may also indicate a role for drug levels and pharmacokinetics. 14,43 In some of our LT patients, virus half-life during the first phase decline appears longer than that published for non-immunosuppressed individuals, but consistent with the range observed (1. [13][14][15][16][17][18][19].0) in the only other available study exploring this variable in treated LT-recipients.…”

“…[24][25][26][27][28][29] In addition, some LT/CsA patients showed delayed monophasic (single exponential) declines. We therefore limited the Table 1 Demographic, clinical, and epidemiological characteristics of the study population and treatment outcomes.…”