Highly active antiretroviral therapy does not protect against Kaposi's sarcoma in HIV-infected individuals

The introduction of highly active antiretroviral therapy (HAART) in clinical practice has dramatically altered the natural history of HIV disease [1]. In this context, a steady decline in the incidence of Kaposi's sarcoma (KS) has been attributed to the increasing use of HAART in recent years [2]. Furthermore, a number of reports have documented tumour regression after the initiation of HAART [3]. On the basis of these observations, the current management of patients presenting with asymptomatic cutaneous KS is to treat the underlying HIV infection optimally with HAART. Recently, a case was reported in which KS progression was documented despite continued therapy with protease inhibitor-based HAART [4]. We describe here six patients: four with newly developed KS at the time of initial virological and immunological response to HIV therapy, one with newly diagnosed KS and one with a recurrence of KS, both after long-term successful treatment of their HIV infection with HAART (see Table 1). Interestingly, ‘intensification’ of the antiretroviral therapy regimen did not affect the short-term course of the KS in the two latter cases.Table 1: Demographics, clinical and laboratory features of six HIV-positive men who presented with Kaposi's sarcoma while responding to highly active antiretroviral therapy. All six patients presented with widespread skin lesions. Two had mucosal involvement and one of these had further massive nodal involvement. In patients 1–5, this was the initial KS episode. Patient 6 had previously achieved a complete remission from widespread cutaneous KS with zidovudine, zalcitabine and daily IFNα-2a, remaining in complete remission for 56 months. The KS relapse was diagnosed 35 months into a successful course of HAART. Pathological examination of skin biopsies from lesions on each of the six patients was typical of KS. KS has been linked to a latent infection with human herpes virus (HHV)-8 [5]. The pathogenesis of AIDS-related KS involves a complex interaction between HHV-8, HIV regulatory genes and inflammatory cytokines [6]. The alternation of cytokine homeostatis has been described upon the initiation of HAART. The precise mechanism by which HAART modifies the clinical course of KS has, however, not yet been elucidated [7]. The patients described here developed mucocutaneous KS, while having initial or long-term virological and immunological response to HAART. Four of them were antiretroviral therapy naive and became symptomatic within 20 weeks of starting therapy. This clinical pattern resembles the immune reconstitution syndrome associated with other AIDS-related diseases. A mycobacterium immune reconstitution syndrome has been well characterized in patients with a subclinical Mycobacterium avium complex disease [8]. Similarly, patients with Mycobacterium tuberculosis infection, ocular cytomegalovirus, cryptococcal infection and hepatitis C infection have experienced recrudescence of symptoms while responding to combination antiretroviral therapy [9–12]. Of note is the fact that a cluster of cases of multicentric Castleman's disease, another HHV-8-related condition, was recently reported shortly after the initiation of HAART [13], as have been other AIDS-related opportunistic infections. Two of our patients developed new onset or re-emergent KS several years after the initiation of successful antiretroviral therapy. Of note is the fact that the intensification of antiretroviral therapy failed to control the emergence of KS in the latter two patients. Our case series, therefore, illustrates the fact that KS can emerge either early or late, despite successful antiretroviral therapy. Whether the early emergence of KS may be related to the recently described immune reconstitution syndrome is unclear at this time. Carlos Zalaa Clawdia Ochoaa Alejandro Krolewieckia Patricia Pattersona Pedro Cahna Richard I. Crawfordb Julio S. G. Montanerb