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AIDS Malignancies in the Era of Highly Active Antiretroviral Therapy

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]

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