Drug interactions between antineoplastic and antiretroviral therapies: Implications and management for clinical practice.

Despite the impact of combined antiretroviral therapy (cART) on human immunodeficiency virus (HIV)-related mortality, malignancies remain the second most common cause of death in HIV infection in developed countries. In addition to the AIDS-defining malignancies, other cancers such as Hodgkin's lymphoma and anal cancer, are more frequent in HIV-infected patients who survive longer even though they do not have complete immune restoration The use of concomitant antineoplastic chemotherapy and cART have been demonstrated to be feasible and effective in patients with HIV-related malignancies; however, many drugs used in cART regimens have the potential for causing drug interactions as a result of their ability to either inhibit or induce the cytochrome P450 (CYP) enzyme system. Since many antineoplastic drugs are also metabolised by the CYP system, co-administration with cART could result in either drug accumulation and possible toxicity, or rapid drug metabolism and decreased efficacy. Unfortunately, very limited prospective interaction data are available to safely guide the combined use of cART and chemotherapy. This paper reviews the potential drug interactions and therapeutic considerations of the antiretroviral agents used to treat HIV and the most common anticancer agents used in the treatment of malignancies found in patients with HIV infection.

[Tuberculosis and infliximab treatment. National surveillance from January 1, 2000, through June 30, 2003]. / Tuberculoses lors de traitements par l'infliximab. Suivi national du ler janvier 2000 au 30 juin 2003.

OBJECTIVES: Analysis of the tuberculosis cases reported in France in patients treated with infliximab since its marketing approval, assessment of the effect of changes in the summary of product characteristics and national guidelines. METHODS: Based on tuberculosis reports from the national post-marketing adverse drug reaction databank of the manufacturer from January 1, 2000 through June 30, 2003, and records from the national multicenter retrospective survey on opportunistic infections with anti-TNFalpha, we analyzed all cases of tuberculosis and the impact of the changes made in December 2000 in the summary of product characteristics and the guidelines on the prevention and management of tuberculosis in patients treated with infliximab published in February 2002. RESULTS: 56 cases of tuberculosis were reported: the median interval before diagnosis was 12 weeks with a median of 3 infusions. The presence of Koch bacilli was confirmed in 32 patients; 29 patients had extrapulmonary or disseminated forms of tuberculosis. The tuberculosis rate among patients treated with infliximab was greater than among the general population and differed significantly by period (p < 0.005). CONCLUSION: Tuberculosis can occur within the first 12 weeks of treatment with infliximab. Information for practitioners must be continued, together with surveillance of the tuberculosis cases in France.