Malignancies have been detected in approximately 40% of all patients with acquired immunodeficiency syndrome (AIDS) sometime during the course of their illness. These cancers have been both a primary cause of death in some patients and also a source of considerable morbidity. In the current era of highly active antiretroviral therapy (HAART), patients infected with the human immunodeficiency virus (HIV) are surviving longer than ever. HAART appears to have substantially reduced the incidence of Kaposi’s sarcoma (KS) and non-Hodgkin lymphoma (NHL) and may enhance the efficacy of treatment for those patients who do develop these tumors. Unfortunately, HAART has not shown a similar effect on the development of other types of neoplasms, and caring for patients who develop malignancies in the setting of HIV remains a challenge. Furthermore, HAART is not available universally, with many patients in resource-poor developing countries not having access to antiretroviral drugs.
KS has been the most common tumor associated with HIV infection, but it currently develops in < 10% of homosexual men with AIDS in the United States and in 1% to 2% of other HIV-infected persons. The incidence of KS has declined substantially, from 4.8 per 100 person-years in 1990 to 1.5 per 100 person-years in 1997. In 2003, a European study found that the incidence of KS among HIV-infected individuals was less than 10% of the incidence seen a decade earlier in 1994.
Among AIDS patients in the United States, the incidence of KS is higher in males than in females. There is also a higher incidence of KS in men than in women in Africa (male-female ratio, 2:1), despite the equal prevalence of HIV infection among men and women.
The age distribution of AIDS-related KS follows the distribution of HIV infection. As such, AIDS-related KS can occur in all age groups. In American adult males, the most common age of onset of AIDS-related KS is 30 to 40 years old. No peak age has been reported.
No racial or ethnic differences in the incidence of AIDS-related KS have been observed.
In the United States, KS is seen in < 10% of homosexual men with AIDS. The proportion of KS among AIDS-defining diagnoses is lower in parts of Europe, where there are proportionately fewer male homosexual AIDS cases (eg, 6.8% of Italian AIDS patients), and higher in parts of Africa, where KS is endemic in the non–HIV-infected population. Among AIDS cases in the United States, the proportion of patients with KS has declined from the beginning of the AIDS epidemic, possibly as a result of changes in high-risk sexual behavior among homosexual men and the wider use of more effective antiretroviral combination regimens.
Etiology and risk factors
In 1994, unique viral DNA sequences were identified in tumor tissues from patients with AIDS-related KS, which led to the identification of a new virus called KS-associated herpesvirus (KSHV) or human herpesvirus type 8 (HHV-8). HHV-8 has been found in > 90% of AIDS-KS tumors, as well as in classic KS, endemic African KS, and post–organ transplant-related KS. It has also been identified in body cavity–based lymphoma/primary effusion lymphoma, multicentric Castleman’s disease, and angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) in HIV-infected patients.
HHV-8 may be transmitted through sexual contact, blood products, or organ transplantation. The seroprevalence of HHV-8 in AIDS-related KS is nearly 100%. HHV-8 has been found in high concentration in the saliva of patients with KS.
HHV-8 is critical in the pathogenesis of AIDS-related KS. The mechanism by which HHV-8 induces KS in susceptible individuals is the subject of intense current investigations.
Environmental and host factors
Various environmental and host factors, including HIV- and HHV-8–induced cytokines, AIDS-associated infections, the host’s hormonal milieu, immunosuppression, and antiretroviral therapy, may induce or suppress the development of KS and alter its growth.