Safety and efficacy of interferon-ribavirin combination therapy in HCV-HIV coinfected subjects: an early report

Abstract

Background-More severe liver disease together with a poor response rate to interferon argue for the use of more potent anti-hepatitis C virus (HCV) therapies in human immunodeficiency virus (HIV)-HCV coinfected patients, but the eYcacy and safety of interferonribavirin combination therapy in HIV infected subjects are unknown. Aim-To retrospectively evaluate the eYcacy and safety of anti-HCV combination therapy in 21 HCV-HIV coinfected patients receiving antiretroviral therapy, and to access the clinical relevance of in vitro inhibition of phosphorylation by ribavirin of potent inhibitors of HIV-that is, zidovudine, stavudine, and zalcitabine. Patients-Twenty one patients were treated with combined antiretroviral therapy including zidovudine (n=8) or stavudine (n=13) (in association with protease inhibitors in 12). All received ribavirin (1000 or 1200 mg/day) and interferon (3 MU three times/week) for chronic hepatitis C infection. All patients had not responded (n=20) or relapsed (n=1) after a previous six month course of interferon therapy. Methods-HIV viral load (Monitor test)and CD4 cells count were measured at the beginning and every three months during and after ribavirin plus interferon therapy over a mean period of 11 (1) months. Clinical and biological adverse eVects were recorded. Results-There was no significant variation in HIV viral load or CD4 cell counts after three or six months of ribavirin therapy compared with baseline values. Of the 21 subjects, three (14%) had an increase in HIV viral load of more than 0.5 log leading to discontinuation of ribavirin in one. Eleven of 21 (52.4%) had initial negative HCV viraemia at three (n=10) or six (n=1) months but only six were polymerase chain reaction negative at the end of therapy, leading to rates for primary response and breakthrough of 23.8% and 28.5%, respectively. Six months after completion of therapy, three patients relapsed (14.3%) and three (14.3%) had sustained virological response. Median haemoglobin concentration decreased significantly after three and six months of ribavirin therapy (p= 0.0002 and p=0.0003, respectively) leading to withdrawal of therapy in one patient. Conclusions-These preliminary results show that: (1) despite in vitro interactions between ribavirin, zidovudine, and stavudine, significant variation in HIV replication does not usually occur in HCV-HIV coinfected patients receiving ribavirin and diVerent antiretroviral regimens, including zidovudine and stavudine; (2) interferon and ribavirin combination therapy induced primary and sustained virological responses in 28.5% and 14.3% of treated subjects (who were previous non-responders to interferon therapy), respectively; (3) anaemia is a frequent adverse event. Such results should be confirmed in larger prospective trials. (Gut 2000;47:694-697)

Relationships between Serum IGF-1, IGFBP-2, Interleukin-1Beta and Interleukin-6 in Inflammatory Bowel Disease

“…The correlations of IGF-1 with ESR and CRP could indicate an effect of the inflammatory status on IGF-1 synthesis and secretion, consistent with data in newly diagnosed adult patients with CD and UC in whom reduced IGF-1 levels have been suggested to be induced by inflammatory cytokines [25]. The influence of inflammation per se on growth failure in CD has been little studied; however, in a rat model of colitis up to 40% of linear growth impairment occurred as a direct effect of inflammation [26]. …”

Interferon and ribavirin combination therapy for chronic hepatitis C in human immunodeficiency virus–infected patients with congenital coagulation disorders

“…This figure is 2-to 3-fold higher than those obtained in HIV-infected nonhemophiliac patients given interferon monotherapy 14,15 and similar to those reported among HIV-HCV-coinfected drug users given interferon and ribavirin combination therapy for 6 to 12 months. [23][24][25][26] As in immunocompetent patients, there was a tendency towards a higher sustained response rate among patients with genotype 2 or 3 (80%) as compared with those with genotype 1 or 4 (27%). Because the present study was designed before data from international trials on combination therapy became available, 18,19 all primary responders at 6 months were intended to complete a 12-month course of treatment irrespective of their HCV genotype.…”

“…This finding is in agreement with those reported in similarly treated HIV-infected drug users. [23][24][25][26]28 Mean absolute numbers of CD4 ϩ cells did not change significantly during or after treatment, although a transient decrease was observed in 10 patients, which was counterbalanced by a proportional increase in the remainder. Similarly, no significant change in the proportion of CD4 cells over the total lymphocyte count during the treatment or follow-up was observed.…”

Therapie der Hepatitis-C-Infektion

“…Eine Behandlung mit Interferon-α Monotherapie hat vergleichbare Ansprechraten mit HIV-negativen Patienten gezeigt [34]. Erste Daten zur Kombinationstherapie von IFN-α + Ribavirin zeigen, dass diese Behandlung auch bei HIV-Patienten sicher und effektiv zu sein scheint [35] (siehe auch Beitrag von J. Rockstroh in diesem Heft).…”