Abstract
BACKGROUND: The impact of highly active antiretroviral therapies (HAART) on the risk of non-AIDS-defining cancers (NADCs) and the role of biological and clinical factors in their pathogenesis are debated issues. The purpose of this review is to examine the epidemiology, etiology, and not-yet-defined pathogenic characteristics of NADCs and discuss topics such as treatment strategies, comorbidity, and multidrug interactions. Four types of NADCs that deserve special attention are examined: anal cancer, Hodgkin lymphoma (HL), hepatocellular carcinoma, and lung cancer. METHODS: The PubMed database and the Cochrane Library were searched by focusing on NADCs and on the association among NADCs, HAART, aging, and/or chronic inflammation. All articles were reviewed to identify those reporting variables of interest. RESULTS: NADC incidence is twofold higher in patients with HIV/AIDS than in the corresponding general population, and this elevated risk persists despite the use of HAART. The mechanisms that HIV may use to promote the development of NADCs are presently unclear; immunological mechanisms, either immunodeficiency and/or immunoactivation, may play a role. CONCLUSION: Recent clinical studies have suggested that equivalent antineoplastic treatment is feasible and outcome can be similar in HIV-infected patients on HAART compared with uninfected patients for the treatment of HL and anal and lung cancers. However, patients with advanced HIV disease and/or aging-related comorbidities are likely to experience worse outcomes and have poorer tolerance of therapy compared with those with less advanced HIV disease.