Graduated Systemic Treatment of AIDS-Associated Kaposi Sarcoma

Abstract

Kaposi sarcoma is a mesenchymal tumor involving blood and lymphatic vessels. It is the most common malignancy in HIV-infected patients and is classified as one of the AIDS-defining diseases. First described as early as 1872, it is only in recent years that deeper insights into the pathogenesis of Kaposi sarcoma have been gained; Kaposi sarcoma represents an extraordinary example of viral oncogenesis and growth control by the immune system. Although the incidence of HIV-related Kaposi sarcoma as the initial manifestation of AIDS has recently decreased, the overall prevalence of the disease remains stable. To date, AIDS-associated Kaposi sarcoma (AIDS-KS) remains a major cause of severe disease complications and fatal outcome in HIV-positive homosexual men. The initial success of systemic interferon-α (IFNα) treatment in AIDS-KS occurred before the identification of the human herpes virus (HHV)-8 (Kaposi sarcoma herpes virus [KSHV]) and in the absence of a coherent view of Kaposi sarcoma pathogenesis. Over the past several years a more comprehensive understanding of how Kaposi sarcoma develops and why the neoplasm occurs at increased virulence in HIV-infected persons has been established. HHV-8 can be found in all types of Kaposi sarcoma, whether related to HIV or not. In the era of highly active antiretroviral therapy (HAART), regression of AIDS-KS has been observed with pure antiretroviral therapeutic regimens. A revival of local therapy of Kaposi sarcoma may occur, if HAART therapy is shown to prevent spreading of Kaposi sarcoma disease. In fact, Kaposi sarcoma is not so much the result of immunodeficiency but the result of immune activation triggered by inflammatory cytokines, which can be partly antagonized by IFNα. In advanced Kaposi sarcoma, conventional chemotherapy used to be a double-edged treatment strategy as it counteracts the reconstitution of the immune system. However, novel agents, for example, pegylated liposomal doxorubicin or daunorubicin, selectively target the tumor with better response rates and less cumulative toxicity than with all other chemotherapies. This article reviews the rationale for and results with graduated systemic therapy of patients with AIDS-KS to yield a more comprehensive treatment approach for this extraordinary malignancy.