Though rates of Kaposi's sarcoma (KS), an AIDS-related skin cancer, continue to fall, the disease is being diagnosed more often in people at higher CD4 counts, according to a study published in the November 27 issue of AIDS.

KS was once a common and defining feature of AIDS. Not only were the deep-purple skin lesions disfiguring, but they could even be fatal if the cancer spread to the lungs and other organs. When potent combination antiretroviral (ARV) therapy became available at the end of 1995, providers noticed something promising: People with KS who went on these new therapies often saw improvement in the cancer. Some people's KS cleared completely and never came back.

Subsequent research has confirmed these early findings. Rates have steadily decreased since the mid-1990s. More recently, however, studies have begun to suggest that the disease, which most commonly appeared at lower CD4 counts, is being diagnosed in people with much higher CD4 counts today.

To explore this suggestion further, Nancy Crum-Cianflone, MD, from the Naval Medical Center in San Diego, and her colleagues studied the medical records of 5,067 HIV-positive people enrolled in the U.S. Military HIV Natural History Study between 1995 and 2008. Crum-Cianflone and her colleagues broke down the data from the study into four separate time periods, 1985 to 1990, 1991 to 1995, 1996 to 2001, and 2002 to 2008. During the course of the study, 247 people were diagnosed with KS.

Crum's team found that rates of KS plunged dramatically between 1985 and 2008. The rate of KS diagnoses in the 2002 to 2008 time period were 72 percent lower than in the 1985 to 1990 time period. What's more, the strongest predictor of developing KS was time spent with a CD4 count of less than 350 and that for every 50 cell drop in CD4 cells, the risk of KS increased. Thus, earlier studies were accurate: KS tends to strike people with low CD4 counts, and rates of the disease have fallen significantly since combination ARV therapy was introduced.

Crum and her colleagues also found, however, that the proportion of people diagnosed with KS at higher CD4 counts actually increased over time. While 18 percent of KS diagnoses occurred in people with CD4 counts of 350 and above between 1985 and 1990, and dropped further between 1991 and 2001, 35 percent of all KS diagnoses between 2002 and 2008 occurred in people with higher CD4s.

The study doesn't say that the nature of KS has changed, or that it is now more likely to strike people with high CD4 counts. Instead, it indicates that KS rates have dropped more dramatically in those with low CD4 counts, but that they haven't fallen as much in those with higher CD4s. The end result: the proportion of people diagnosed at lower CD4s falls, resulting in an increase in the proportion of people diagnosed at higher CD4s. This could be due to the fact that until very recently, most people didn't start ARVs until their CD4 counts fell below 350.

Though the study did not explicitly look at the role of ARV therapy on the rates of diagnoses or on the effect on diagnoses at higher CD4s, the authors do state that there was a suggestion that people at higher CD4s who were on ARV therapy had a lower risk of KS diagnoses than people with high CD4s who were not on HIV medication. This would square with many other studies showing that ARVs significantly minimize the risk of KS and that when KS does strike such individuals, they tend to have a much less aggressive form of the disease.

“Given these trends, determining whether [combination ARV] use at higher CD4 cell counts will reduce the impact of Kaposi's sarcoma is of clinical importance,” the authors stated. They conclude: “Future studies are needed to determine whether earlier HAART initiation will further decrease the burden of Kaposi's sarcoma among HIV-infected persons.”