Therapy of special HIV-associated diseases: HCV-HIV-co-infection and AIDS-related Kaposi's sarcoma - official satellite to the 7th European Conference on Clinical Aspects and Treatment of HIV-infection, October 23, 1999 in Lisbon, Portugal.

BACKGROUND: In the era of highly active antiretroviral therapy (HAART), certain complications of HIV-disease as e.g. opportunistic infections and Kaposi s sarcoma (KS) have significantly diminished. New insights in pathological pathways revealed the role of co-viruses as HHV-8 and HCV so that in our days AIDS-associated KS and chronical hepatitis C (CHC) in HIV-infected persons can be considered as the result of opportunistic infections with HHV-8 or HCV respectively. - Though the overall incidence of AIDS-KS is declining, it remains as a reason of severe disease complication and fatal outcome. Actual therapeutic strategies have to be evaluated regarding safety and efficacy as a major option, while cost-effectiveness of treatment and quality of life aspects for the patient must also be included to assess a successful disease management within the up to now merely palliative setting. HIV-infection evidently triggers the natural course of CHC in terms of more progressive liver disease. Otherwise there seems to be no clinical benefit of HAART on CHC. Until recently IFN-alfa treatment was the only therapy available for patients with CHC. As initial therapy with a combination of IFN-alfa and ribavirin turned out to be more effective than IFN-monotherapy in HCV-infected persons, it has now to be considered to include anti-HCV-combination treatment into the therapeutic program of HIV-HCV-coinfected patients under HAART. - Within the 7th European Conference on Clinical Aspects and Treatment of HIV-Infection, which took place in Lisbon from October 23 to 27 1999, a satellite symposium was organized to evaluate actual treatment options in the management of special HIV-associated complications focussing on AIDS-KS and HCV-HIV-coinfection.

METHODS: To evaluate the safety and efficacy of IFN-alfa-2b and ribavirin combination therapy in patients with CHC, a total of 1773 treatment-naive patients was recruited in two phase III clinical trials. They were randomized in 4 treatment schedules to receive IFN-alfa-2b plus ribavirin or placebo for 24 weeks or 48 weeks respectively. Cost-effectiveness data compared treatment with liposomal daunorubicin and pegylated liposomal doxorubicin in AIDS-KS-patients within two phase III studies. The assumptions were a comparable efficacy, gastrointestinal toxicity, and frequency of opportunistic infections (OI). A quality-of-life-study on KS-treatment with pegylated liposomal doxorubicin (PLD, Caelyx(R)) was based on a phase III study with an overall median survival of 160 days for the patients, who completed questionnaires with 30 items specific for HIV-related diseases. The health-related quality-of life (HRQL) assessment and analysis includes 11 domains, in which improvements were calculated within a multiple analysis to be significant if they are higher than 10 (at a 0-100 scale).

RESULTS: In 1775 treatment-naive patients with CHC, response rates to a combination therapy of IFN-alfa-2b with ribavirin was significantly higher in all patient groups with more than 60% of sustained virological response in patients with genotype 2 and 3, while patients with genotype 1 (poorer prognosis) benefit from extended duration from 24 to 48 weeks (17% versus 29% of sustained virological response). - Pegylated liposomal doxorubicin (PLD, Caelyx(R)) in the treatment of AIDS-related KS is more effective and less toxic than BV or ABV. Cost-effectiveness analysis suggests that PLD is preferable over liposomal daunorubicin, BV and ABV. Regarding the HRQL-assessment, PLD came out to be superior in 9 of 11 domains tested, with the greatest improvement in general health and pain relief.

CONCLUSIONS: As the combination therapy of IFN-alfa-2b with ribavirin is the first treatment in CHC, there is an urgent need to consider the therapeutical strategies in this field in HCH-HIV coinfected patients. (ABSTRACT TRUNCATED)