Highly Active Antiretroviral Therapy Dramatically Reduces Incidence of Kaposi’s Sarcoma

LONDON—Since the introduction of highly active antiretroviral therapy (HAART), the incidence of HIV-related Kaposi’s sarcoma has plummeted (ASCO abstract 1639). "Of the more than 4,500 HIV-positive patients we’ve been following since January of 1996 in the post-HAART era, about two-thirds have been on HAART," said lead investigator Mark Bower, FRCP, PhD, consultant in oncology at Chelsea and Westminster Hospital in London. "The chance of developing Kaposi’s sarcoma is dramatically reduced in those patients on antiretroviral therapy."

The Chelsea-Westminster cohort is the largest prospectively collected HIV cohort in Europe, comprising 8,636 HIV-positive patients, including 1,023 patients (1,012 male) with Kaposi’s sarcoma, and representing 44,864 patient years of follow-up. Numerous other cohort studies have confirmed a decline in the incidence of HIV-related Kaposi’s sarcoma since the HAART era.

Pre- and Post-HAART

In this study, investigators compared 831 cases of Kaposi’s sarcoma in the pre-HAART era, from 1988 to 1995, with 192 cases in the HAART era, from 1996 to 1999. Age at diagnosis of Kaposi’s sarcoma was lower in the pre-HAART era (mean 36.7 years vs 38.7 years, P = .002) and the CD4 cell count was lower (mean 129/µL vs 187/µL, P < .0001).

In the HAART era, only 58/192 (30.2%) were receiving HAART at the time Kaposi’s sarcoma was diagnosed. In 137 of 192 patients (71.4%), Kaposi’s sarcoma was the first HIV-associated diagnosis. Although nadir CD4 cell count before diagnosis of Kaposi’s sarcoma (mean 141/µL) in patients on HAART was similar to that in patients not on HAART, those patients who were on HAART at the time of Kaposi’s sarcoma diagnosis had higher CD4 cell counts (mean 203/µL vs 136/µL, P = .002), suggesting that the Kaposi’s sarcoma did not develop because of failure of the HAART.

Kaposi’s Sarcoma in HAART Era

"Highly active antiretroviral therapy has reduced the incidence of Kaposi’s sarcoma, prolongs the time to treatment failure, and may lead to Kaposi’s sarcoma resolution in those affected," said coauthor Mark Nelson, MA, MBBS, consultant in genitourinary medicine at Chelsea and Westminster Hospital. "We found that in the HAART era, Kaposi’s sarcoma diagnosis usually coincided with that of HIV. Those individuals who develop Kaposi’s sarcoma while receiving HAART are usually experiencing treatment failure."

Multivariate analysis showed that three factors influence the risk of developing Kaposi’s sarcoma in the HAART era: age, nadir CD4 count, and antiretroviral use, Dr. Bower explained. Age has a tiny but significant effect, so that risk of developing Kaposi’s sarcoma increases with increasing age. The lower the nadir CD4 count, the higher the risk of developing Kaposi’s sarcoma.

The most important factor is antiretroviral usage, which reduces risk of Kaposi’s sarcoma by 60%. Of all patients who developed Kaposi’s sarcoma since 1996, 85% had never taken HAART. In the 15% of patients who developed Kaposi’s sarcoma despite taking HAART, about 80% of them had HIV viremia, suggesting that HAART therapy had failed them. Only about 2% of those who got Kaposi’s sarcoma while on HAART, or five patients, had a negative viral load.

"Kaposi’s sarcoma in those on a successful HAART regimen is very rare," Mr. Nelson agreed. "We suggest incomplete immune restoration in these individuals with lack of cytotoxic T lymphocyte activity against human herpesvirus-8."

According to Dr. Bower, the most interesting finding is that protection against Kaposi’s sarcoma by non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART is at least as good, and maybe even better, than that offered by protease-inhibitor based HAART. This is surprising, as earlier work suggests that protease inhibitors protect against Kaposi’s sarcoma by affecting angiogenesis. Nonetheless, it is fortunate, Dr. Bower noted, because NNRTI-based therapy is easier to take, is better tolerated, and has fewer side effects than protease-inhibitor based HAART.

"Further data are being collected regarding the relative efficacies of different HAART regimens in preventing Kaposi’s sarcoma," Mr. Nelson added.

"Earlier studies have shown that NNRTIs are at least as good as protease-inhibitors at controlling HIV, and this work suggests that they are also at least as good at preventing Kaposi’s sarcoma," Dr. Bower said. "In the UK and most of Europe, most clinicians use NNRTI-based HAART predominantly. There’s starting to be a shift now among US HIV specialists toward NNRTI-based HAART as well."