Starting antiretroviral (ARV) therapy significantly increases a person's immune responses to the virus that causes Kaposi's sarcoma (KS), an AIDS-defining cancer. What's more, these data, which were published in the September 10 issue of AIDS, show that a person's KS antibody responses can be restored even in people who wait to start ARVs until their CD4 count is low.

In the early years of the AIDS epidemic, KS was one of the most common forms of cancer in people living with HIV. It was also one of the opportunistic infections that most dramatically responded to the introduction of potent combination ARV therapy in 1996. Not only did ARVs send KS rates plummeting, but they also caused the cancer to disappear in significant numbers of people who already had KS. While ARV therapy's ability to fight this cancer has been well established, scientists are still working to understand how ARVs accomplish this feat.

To shed additional light on this subject, Sheena Sullivan, PhD, from the University of California at Los Angeles, and her colleagues analyzed blood samples from 272 HIV-positive men who have sex with men (MSM) who started ARV therapy between 1996 and 2004. Blood samples were taken roughly one month before the men started ARV therapy and 24 months later. Twenty-two of the men had been diagnosed with KS before starting treatment.

Sullivan and her colleagues tested the blood samples for two types of antibodies—latent and lytic—to the virus that causes KS, the human herpes virus 8 (HHV8). While both latent and lytic antibodies bind to HHV8, they do so at different parts of the virus's life cycle. The team also directly measured levels of HHV8 in the blood.

Seventeen people—seven with KS and 10 without—had measurable HHV8 levels at the time they started ARVs. After 24 months of treatment, 16 of them no longer had measurable HHV8 levels. While seven additional people did develop measurable HHV8 after starting treatment, the level of virus in these individuals was very low.

The most dramatic effect of ARV therapy on KS immunity was found in the development of antibody responses to HHV8. Sullivan's team found that the number of people with HHV8 antibody responses significantly increased after taking ARVs. This effect was most pronounced, however, among those who had KS at the start of the study: They were 22 times more likely to develop an anti-KS antibody response after 24 months of HIV treatment than those who did not have KS before starting treatment.

In terms of those people who tested positive for the HHV8 antibodies only after going on HIV treatment, the authors comment that this was likely not due to people becoming newly infected with HHV8. Rather, people probably did have HHV8 antibodies, but their immune systems were so damaged that they were unable to produce enough antibodies for the test to recognize them.

Intriguingly, Sullivan and her colleagues found that low CD4s at the beginning of HIV treatment were no barrier to developing a strengthened immune response to KS. Older age and higher CD8 levels did, however, diminish the likelihood of a person developing an improved antibody response to KS—a finding similar to other studies.

“Increases in [antibody] immune response may partly explain…the dramatic protection against [KS] offered by [ARV therapy], even when it is initiated at very low CD4 cell counts,” the authors concluded. “[These results] may also apply to [antibody] responses to other viral infections among people with HIV.”