Malignancies in HIV/AIDS

From Epidemiology to Therapeutic Challenges

Paul G. Rubinstein; David M. Aboulafiac; Andrew Zloza

Disclosures

AIDS. 2014;28(4):453-465. 

In This Article

Abstract and Introduction

Abstract

The incidence of AIDS-defining cancers (ADCs) – Kaposi sarcoma, primary central nervous system lymphoma, non-Hodgkin lymphoma, and cervical cancer – although on the decline since shortly after the introduction of HAART, has continued to be greater even in treated HIV-infected persons than in the general population. Although the survival of newly infected people living with HIV/AIDS now rivals that of the general population, morbidity and mortality associated with non-AIDS-defining cancers (NADCs) such as lung, liver, anal, and melanoma are significant and also continue to rise. Increasing age (i.e. longevity) is the greatest risk factor for NADCs, but longevity alone is not sufficient to fully explain these trends in cancer epidemiology. In this review, we briefly review the epidemiology and etiology of cancers seen in HIV/AIDS, and in this context, discuss preclinical research and broad treatment considerations. Investigation of these considerations provides insight into why malignancies continue to be a major problem in the current era of HIV/AIDS care.

Introduction

In late 1995, the first generation of HIV protease inhibitors became commercially available. Within a few months, clinicians were combining these novel drugs with nucleoside and nonnucleoside reverse transcriptase inhibitors. The beneficial effects of what soon became known as HAART were immediate and profound. In just a few years, the number of cases of newly diagnosed AIDS, AIDS-related deaths, and AIDS-defining cancers (ADCs), had decreased by greater than 70%.[1–3] However, even as AIDS-related mortality has continued to decline, the rate of new HIV infections has remained constant.[4–6] Consequently, the number of people living with HIV/AIDS (PLWHA) has increased by a factor of four.[4–6] Although HAART affords PLWHA a longer life expectancy, it also leaves them increasingly vulnerable to the same array of cancers associated with aging that are seen in the general population.[7–12] These non-AIDS-defining cancers (NADCs) include those associated with viral infections [e.g. anal (human papillomavirus, HPV), liver (hepatitis C virus – HCV and hepatitis B virus – HBV), head and neck (HPV)] and those not associated with viral infections (e.g. lung and melanoma). In industrial nations, the number of cases of NADCs now equals or exceeds the number of cases of ADCs, and NADCs are a leading cause of mortality for PLWHA.[3,7–10,13–16] Age and immune status, however, are insufficient to fully explain these trends in cancer risk. For PLWHA, even those with normal CD4+ T-cell counts, the risk for many NADCs remains greater than for their age-matched HIV-seronegative counterparts.[8–10,13,14] Furthermore, compared with the general population, PLWHA present with more aggressive and advanced disease at the time of cancer diagnosis.[17–20] These changes in cancer epidemiology are not well understood. We include preclinical research findings and discuss the epidemiology and etiology of both NADCs and ADCs. We also briefly examine cancer treatment in the context of HAART-chemotherapy interactions.

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