AIDS-Related Kaposis Sarcoma: State of the Art and Therapeutic Strategies

Abstract

In the HAART era Kaposi's sarcoma (KS) remains the second most frequent tumor in HIV-infected patients worldwide, and it has become the most common cancer in Sub-Saharan Africa. In western countries the risk for KS in men having sex with men (MSM) is 5 to 10 times higher compared to other groups of individuals practicing other HIV-risk behaviors. Patients with KS in Sub-Saharan Africa have very high tumor burdens and rapid disease progression with a diminished life expectancy of less than 6 months. KS lesions are comprised of both distinctive spindle cells of endothelial origin and a variable inflammatory infiltrate, which suggests that KS may result from reactive hyperproliferation induced by chronic inflammation, and therefore it is not a true neoplasm. KS has a variable clinical course ranging from very indolent forms, requiring no or minimal therapy, to a rapidly progressive disease. Treatment decisions must take into consideration the extent and the rate of tumor growth, patient's symptoms, immune system conditions and concurrent HIV-related complications. Several different therapeutic options are available but the optimal therapy is still unclear. Highly Active Antiretroviral Therapy (HAART) including protease inhibitors (PI) may represent the first treatment step for slowly progressive disease; chemotherapy (CT) plus HAART is indicated for visceral and/or rapidly progressive disease, whereas maintenance (M)-HAART after systemic chemotherapy may be an effective anti-KS measure after debulking CT. The angiogenic nature of KS makes it particularly suitable for therapies based on targeted agents such as metalloproteinase inhibitors, angiogenesis inhibitors and tyrosine kinase inhibitors. The aim of this article is to provide an up-to-date review of the current status and perspectives of AIDS-related KS in the HAART era.

mTOR as a multifunctional therapeutic target in HIV infection

“…HAART, including protease inhibitors, could represent the first treatment step for slowing progressive disease; chemotherapy plus HAART is indicated for visceral and/or rapidly progressive disease, whereas maintenance HAART after systemic chemotherapy could be an effective anti-KS measure. The angiogenic nature of KS makes it particularly suitable for therapies based on targeted agents such as metalloproteinase inhibitors, angiogenesis inhibitors and tyrosine kinase inhibitors [50].…”

Kaposi Sarcoma in HIV Infected Patients

“…HAART can also lead to complete resolution of KS lesions in patients with good immunological response and limited disease [17]. Simultaneous systemic chemotherapy is indicated in patients with advanced, symptomatic KS [18].…”

Microscopic diversity in oral Kaposi sarcoma

“…The impact and effects are far-reaching, being no more prevalent than in South Africa that is currently home to more HIV-infected persons than any other country. 5,7,8,10,11,15 OKS is most prevalent in epidemic forms of disease, occurring at all stages of HIV infection. End-stage disease (AIDS) correlates strongly with a higher clinical prevalence with lesional aggression indicating immune deterioration, low CD4 cell count and increased HHV-8 viral loads.…”

“…3,8,9 Epidemic KS arising in the context of the HIV/AIDS pandemic remains the most frequent clinical form of disease characterized by the greatest malevolence and poorest prognosis. This is due in part to the presence of overwhelming co-existent neoplastic and infectious disease.…”

“…Disseminated KS in the untreated HIV-positive patient heralds progression to AIDS with many of these patients failing to survive beyond 6-months. 8 More than two thirds of the global HIV-infected population resides in poverty-stricken regions of sub-Saharan Africa, with an estimated 5.6 million sufferers in South Africa alone. 10 Epidemic KS thus constitutes the bulk of our surgical cases with almost no cases of the endemic type identified.…”