AIDS Malignancies in the Era of Highly Active Antiretroviral Therapy

The article by Drs. Gates and Kaplan provides an excellent review of malignancies associated with human immunodeficiency virus (HIV)-1 disease and chronicles the epidemiologic changes seen during the past 5 years. The literature review is very thorough and well balanced.

Since 1981, when acquired immunodeficiency syndrome (AIDS) was first described, we have observed remarkable changes in the epidemiology of malignancies in this country. Previously very rare, Kaposi’s sarcoma (KS) became quite common in HIV-infected patients. In fact, during the early years of the AIDS epidemic, the appearance of KS lesions became a hallmark of the infection and was feared by at-risk populations, especially men who have sex with men. Non-Hodgkin’s lymphoma (NHL) has also increased in incidence, and some experts are concerned that the increase may continue despite recent advances in treatment of HIV disease.

Impact of Potent Antiretroviral Therapy

Widespread use of potent antiretroviral therapy including protease inhibitors (commonly known as HAART) for the treatment of HIV-1 disease has dramatically decreased the incidence of opportunistic infections and death.[1] Unfortunately, as the authors point out, the impact on the risk of developing HIV-associated malignancies is less clear. Kaposi’s sarcoma, arguably the most sensitive to immunosuppression, is certainly much less common now and there have been many reports of regression of lesions.[2] However, NHL has only decreased slightly in incidence during the same period (since 1995). Autopsy studies of HIV-infected cases have shown a marked decrease in opportunistic infections over time, but NHL has not decreased and even shows an upward trend in some studies.[3-5] Apparently, the reconstituted immune system generated by potent antiretroviral therapy may not protect patients against AIDS-related malignancies as well as it does against infections.

The epidemiologic impact on other cancers is less pronounced. As the authors note, lack of relationship to immune deficiency is largely responsible for this in most cases. For example, anal and cervical cancers are common with HIV because of similar risk factors and routes of transmission rather than immunosuppression. Drs. Gates and Kaplan provide a careful review of the available epidemiologic data, including several helpful tables.

Unanswered Questions

While the recent changes in morbidity and mortality from HIV-1 disease in developed countries are gratifying, several unanswered questions remain. Recent developments in pathogenesis research in AIDS malignancies are extremely well reviewed in the article, and the complex issues are clearly described. As the authors frequently point out, the interwoven relationships between HIV-1, other infectious agents, associated malignancies, and the immune system are only beginning to be unraveled. The preexisting immune dysregulation caused by HIV complicates these efforts. Research on host factors in HIV-1 infection to date has focused on control of viral replication, opportunistic infections, and death as end points. The immune system determinants necessary to protect against opportunistic infections are becoming clearer, but the same cannot be said at this time for malignancies.[6]