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AIDS Malignancies in the Era of Highly Active Antiretroviral Therapy

AIDS Malignancies in the Era of Highly Active Antiretroviral Therapy

A dramatic spike in the incidence of Kaposi’s sarcoma
(KS) in never-married men in New York and California in 1981 was one of the
first indications of a new disease now known as acquired immunodeficiency
syndrome (AIDS). We now appreciate a number of mechanisms by which human
immunodeficiency virus (HIV) infection contributes to the pathogenesis of these
tumors. The article by Drs. Gates and Kaplan provides an excellent review of
changes in the epidemiology, presentation, and treatment of these tumors since
the development of potent combination anti-HIV therapy.

Pathogenesis of HIV-Associated Malignancies

As Drs. Gates and Kaplan point out, only a small subset of tumors have a
substantially increased incidence in patients with HIV infection. These include
Kaposi’s sarcoma (KS), systemic non-Hodgkin’s lymphoma (HIV-NHL), and
primary central nervous system lymphoma (PCNSL). With the discovery of a new
herpesvirus now known as Kaposi’s sarcoma-associated herpesvirus (KSHV) by
Chang, et al in 1994,[1] it became evident that the majority of these tumors are
caused by oncogenic viruses.

As is discussed in the article, a number of factors can contribute to the
development of viral-induced tumors in HIV-infected patients. These include (but
are not limited to) failure to control the viral infection immunologically,
activation of the oncogenic viruses by HIV, activation of the viruses by other
opportunistic pathogens, or up-regulation of inflammatory cytokines (such as
interleukin-6) that can promote tumor growth. By contrast, the incidence of most
solid tumors is not increased in patients with AIDS, and this finding must lead
to a consideration of the role that immunologic surveillance may or may not play
in the pathogenesis of those tumors.

Effects of HAART on the Incidence of AIDS-Related Tumors

As HIV infection can promote the formation of various tumors by a number of
different mechanisms, one would expect that the widespread introduction of
highly active antiretroviral therapy (HAART) in 1996 would have differing
effects on the epidemiology of these tumors. As described by Drs. Gates and
Kaplan, such changes have already been observed.

For example, PCNSL develops predominantly in the setting of profound
immunodeficiency. HIV-related immunodeficiency can be partially reversed with
HAART, and as expected, the incidence of this tumor has decreased substantially
since 1996. Infection with KSHV is an essential factor for the development of
KS, and the high percentage of HIV-infected patients with KS during the early
years of the AIDS epidemic was due to widespread coinfection with both viruses.
There is evidence that the incidence of this tumor began to decline as a result
of safer sex practices even before the development of HAART, as well as evidence
that the introduction of HAART has caused a further decline.

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