Cluster of 'indolent' KS cases in older, antiretroviral-treated patients in San Francisco

Doctors in San Francisco have reported a cluster of cases of the AIDS-defining cancer Kaposi’s sarcoma (KS) in older HIV-positive individuals who are doing well on antiretroviral therapy. The cluster was first reported in a letter in the September 27^th edition of the New England Journal of Medicines. Doctors reported seeing nine cases between 2004 and early 2006, but since the publication of this letter, press reports suggest that the number of cases has increased to 15.

KS was one of the first AIDS-defining conditions reported in the early 1980s. Unlike the benign form of KS seen in elderly patients of eastern Mediterranean origin, KS in immunosuppressed HIV-positive patients is often fatal. But unlike KS seen in untreated HIV infection, the cluster of cases seen in San Francisco appears to be more like the form of the malignancy seen in older patients of Mediterranean origin and has been described by physicians as “indolent”: slow to develop or heal, causing little or no pain.

Since the introduction of effective antiretroviral therapy in the mid-1990s the incidence of KS in HIV-positive patients in countries like the US and UK has been declining. Patients with a CD4 cell count of 150 cells/mm³ have the greatest risk of KS, and treatment guidelines specify that antiretroviral therapy should be started before the immune system is weakened to this point. Patients who have already developed KS typically experience a dramatic improvement in their condition after they initiate anti-HIV therapy as their viral load falls and their CD4 cell count increases.

In their letter to the New England Journal of Medicine doctors from San Francisco reported seeing nine cases of KS in HIV-positive patients, all of whom were taking potent antiretroviral therapy and had maintained a CD4 cell count of above 300 cells/mm³ with durable viral suppression.

The KS-affected patients had a median age of 51 years (range, 41 – 74) and had been living with diagnosed HIV infection for a median of 18 years (range, four to 24 years). The median duration of antiretroviral therapy was seven years (range, under one year to 19 years). The patients had well-preserved immune function when they initiated antiretroviral therapy, the median nadir CD4 cell count being 340 cells/mm³ (range, 90 – 455 cells/mm³). None of the patients had a history of other AIDS-defining infections.

None of the patients became physically unwell because of KS. The doctors write, “the patients have had a relatively indolent course of Kaposi’s sarcoma, with no eruptive cutaneous lesions, visceral involvement, or other AIDS-defining illnesses.”

The additional six cases reported in the San Francisco Chronicle have had similar characteristics.

A case of KS in a patient taking successful antiretroviral therapy was reported in 1999 (Chan et al), but doctors in San Francisco believe that they have been able to see this cluster because the city has “a high number of aging patients who are infected with both HIV and human herpesvirus 8” (the underlying cause of KS).

It has been suggested that antiretroviral regimens that include a protease inhibitor should be used in patients with KS because it is thought that this class of drugs have activity against the condition. However, in the San Francisco cluster, “seven patients have been receiving protease inhibitors without improvement in their Kaposi’s sarcoma.”

“These patients present a clinical and prognostic conundrum” conclude the authors, “they are receiving maximal antiretroviral therapy yet have persistent Kaposi’s sarcoma. This phenomenon may increase in frequency as the HIV-infected population ages, and we recommend that physicians monitor this group carefully.”