Efficacy and tolerability of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected persons.

BACKGROUND: Treatment options for anogenital warts in patients with HIV-1 are unsatisfactory because they fail to eradicate latent human papillomavirus. GOAL: To determine tolerability and efficacy of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected patients. STUDY DESIGN: A randomized, placebo-controlled, single-blind, crossover pilot study of either 1% cidofovir cream or placebo applied once daily 5 days a week for 2 weeks followed by 2 weeks of observation was performed. RESULTS: Six patients were randomized to 1% cidofovir cream and six to placebo. The latter patients eventually received 1% cidofovir cream. Thus, 12 treatment rounds of cidofovir were compared with six rounds of placebo. A reduction of more than 50% in the total wart area achieved by seven cidofovir treatments (58%), as compared with no placebo regimen (P = 0.02). Local reactions occurred in 10 of the 12 patients treated with cidofovir, as compared with 0 of the 6 subjects in the placebo group (P < 0.001). CONCLUSIONS: For the initial clearance of anogenital warts in HIV-infected patients, 1% cidofovir cream is significantly more effective than vehicle cream. Local mucosal erosion is a common side effect.

Pilot dose-finding trial on interferon alpha in combination with ribavirin for the treatment of chronic hepatitis C in patients not responding to interferon alone.

BACKGROUND: Effectiveness of combination therapy with standard interferon alpha doses and ribavirin is far from being demonstrated in patients with hepatitis C non responders to interferon alpha monotherapy. Recent kinetic studies revealed that these doses may be suboptimal. AIMS: To find the criteria for optimisation of the interferon dose, to be used in combination with ribavirin in patients with hepatitis C non responders to interferon alpha monotherapy. PATIENTS: Sixty-three patients enrolled in a pilot controlled trial were treated for 6 months with ribavirin ([1000-1200 mg daily) and were randomised to concurrently receive interferon alpha 2b for 6 months at: 3 Million Units thrice weekly [group A (21 patients)], 5 MU thrice weekly [group B (21 patients)] and 5 million units daily [group C (21 patients)]. RESULTS: A sustained virological response was observed in: 1 patient from group A (5%), 2 patients from group B (9%) and 8 patients from group C (38%; p=0.02 vs group A; p=0.03 vs group B). Side-effects were not significantly different between the 3 groups. Multivariate analysis showed that infection by hepatitis C virus genotypes 2 or 3 and interferon alpha dosage of 5 million units daily were independent predictors of sustained response. CONCLUSIONS: These results suggest that higher interferon doses administered daily in combination with ribavirin could be more effective in those patients with hepatitis C who had not responded to interferon alone.

Decrease of HCVRNA after three days of daily interferon treatment is predictive of the virological response at one month.

Early monitoring of HCVRNA during interferon treatment may allow clinicians to obtain important information that could help them to adopt therapeutic decisions in individual cases. The hepatitis C virus infection is highly dynamic and a daily high dose of IFN may induce a decline of viremia of 95+/-10% of baseline value after 24 to 48 hours of treatment. The importance of this early antiviral efficacy has not been understood. We have measured HCVRNA levels in 47 patients with chronic hepatitis C infection during interferon treatment to study HCVRNA kinetics and evaluate the predictive value of the early decay of viremia on the virological response after one month of treatment. Sixty percent of treated patients showed early virological response (EVR) and it was significantly associated with low HCVRNA levels and a genotype other than 1b. Finally, the absence of an 85% decline in HCVRNA levels after 3 days of treatment observed in 11 out of 45 patients (24%) was an absolute and very early predictor of the absence of EVR in the study population.

High prevalence of peripheral neuropathy in hepatitis C virus infected patients with symptomatic and asymptomatic cryoglobulinaemia.

BACKGROUND: Fifty per cent of patients with chronic hepatitis C, show detectable cryoglobulinaemia, even though most of them do not show cryoglobulinaemia related symptoms. Peripheral neuropathy is present in most of the patients with symptomatic cryoglobulinaemia, where it may be the first clinical manifestation. The prevalence of peripheral neuropathy in patients with hepatitis C and cryoglobulinaemia is unknown. AIMS: To assess the prevalence of peripheral neuropathy in HCV infected patients with symptomatic or asymptomatic detectable cryoglobulinaemia. PATIENTS AND METHODS: Eighty-nine patients with HCV infection and detectable cryoglobulinaemia underwent electrophysiological studies. RESULTS: Electrophysiological evidence of peripheral neuropathy was found in 37% and was significantly associated with: the presence of cryoglobulinaemia syndrome, older age, higher rheumatoid factor reactivity and immunoglobulin M levels and reduced complement C4 activity. However, electrophysiological evidence of peripheral neuropathy was unrelated to cryocrit levels and type of cryoglobulinaemia and was found in 23/68 patients without any symptoms of cryoglobulinaemia other than pain and paresthesia. CONCLUSIONS: These findings suggest that peripheral neuropathy is frequent in patients with hepatitis C and detectable cryoglobulins. Neuropathy was found to be present in 1/3 of patients without other cryoglobulinaemia-related symptoms, thus a direct or indirect role of HCV, independent of cryoglobulinaemia, in the pathogenesis of nerve damage cannot be ruled out.

Treatment of chronic hepatitis D with interferon alpha-2b in patients with human immunodeficiency virus infection.

BACKGROUND/AIMS: Hepatitis delta virus (HDV) coinfection is frequent in patients infected with human immunodeficiency virus (HIV), and it may cause death independently of the development of full-blown AIDS. In order to evaluate the efficacy and tolerability of interferon alpha in the treatment of hepatitis delta in HIV-infected patients, and to compare them with those observed in anti-HIV-seronegative patients, we carried out an open uncontrolled trial on 21 HIV-uninfected and 16 HIV-infected patients without severe immunodeficiency. METHODS: All patients were treated with recombinant interferon alpha 2b (IFN) at doses of 10 million units thrice weekly for 6 months, and 6 million units thrice weekly for an additional 6 months. Patients showing alanine transaminase activity values persistently reduced by at least 50% from basal values received an additional 1-year course of 3 million units thrice weekly. RESULTS: Alanine aminotransferase normalization was observed in 19% of HIV-infected and 14% of HIV-uninfected subjects during the first year; in 12% of HIV-infected and in 9% of HIV-uninfected patients during the second year. Twenty-five percent of HIV-infected and 14% of HIV-uninfected patients stopped IFN because of poor compliance or side effects. Two years after stopping interferon treatment, one anti-HIV-seropositive and two anti-HIV-seronegative patients showed complete persistent biochemical, virological and histologic remission. CONCLUSIONS: Long-term efficacy and toxicity of IFN treatment seem not to be different in HIV-infected and -uninfected patients with delta hepatitis; given the overall poor rate of long-term response, IFN treatment could be considered only in immunocompetent HIV-HDV-coinfected patients, strictly selected because of rapidly evolving liver disease.