Implications for practice

HAART may delay the onset of KS as an AIDS-defining diagnosis in patients with HIV infection. HAART may also induce responses in AIDS-related KS via immune reconstitution but the response to therapy is unpredictable. Patients with high viral loads, low CD4 counts or with other HIV-related symptoms require antiretroviral therapy for control of HIV infection. HAART alone in these patients is a reasonable initial therapy for KS, which may be combined later with other local or systemic treatments. However, immune reconstitution takes several weeks and patients with poor prognosis KS may require additional therapy in the interim.

What is the role of anti-herpes virus therapy in the prevention and treatment of AIDS-related

Kaposi's sarcoma?

The discovery of KSHV (also known as HHV8) has provided another potential target for the prevention and treatment of AIDS-related KS. KSHV replication is inhibited in vitro by cidofovir, ganciclovir and foscarnet, but not by aciclovir.89,90 Cohort studies have reported a decreased risk of developing KS for HIV-positive patients treated with ganciclovir or foscarnet for cytomegalovirus (CMV) infection and there have been occasional case reports of patients with AIDS-related KS having prolonged responses to antiherpetic therapy.91-95 One cohort study of 3688 HIV-positive patients followed up for a median of 4-2 years, during which time 16% (598 patients) developed KS, found a statistically significant reduction in the relative hazard of developing KS for those who received foscarnet or ganciclovir. The relative hazard for foscarnet was 0-38 (95% CI 0-15-0-95; P = 0-038) and for ganciclovir 0-39 (95% CI 0-19-0-84; P= 0-015).

A randomised study of the treatment of CMV retinitis with ganciclovir in patients with AIDS, found a reduced risk of developing KS with oral or intravenous ganciclovir treatment.96 The 377 patients with AIDS and unilateral CMV retinitis were randomised to receive a ganciclovir implant and oral ganciclovir, 4-5 g daily, ganciclovir implant and oral placebo, or intravenous ganciclovir alone. The primary outcome was the development of new CMV disease but treatment with oral or intravenous ganciclovir was also found to reduce the risk of developing KS by 75% (P= 0-008) and 93% (P<0-001), respectively, compared with oral placebo.96

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