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Patterns of lymphotropic herpesvirus viraemia in HIV-infected patients with Kaposi's sarcoma treated with highly active antiretroviral therapy and liposomal daunorubicin

2000; Lippincott Williams & Wilkins; Volume: 14; Issue: 14 Linguagem: Inglês

10.1097/00002030-200009290-00026

1473-5571

José Miguel Cisneros, Francisco Pozo, Raquel Serrano, Elisa Vidal, Antonio Rivero, Antônio Tenório,

Cytomegalovirus and herpesvirus research

Highly active antiretroviral therapy (HAART) and liposomal doxorubicin can be effective in controlling Kaposi's sarcoma (KS) [1,2]. The aim of this study was to determine the patterns of lymphotropic herpesvirus viraemia in HIV-infected patients with KS and to study whether the clearance of human herpesvirus (HHV) type 8 viraemia correlates in any way with the presence of other herpesviruses. Seven naive HIV-positive patients received 40 mg/m2 liposomal daunorubicin (Daunoxome, Nexstar Pharmaceuticals, CA, USA) every 2 weeks. HAART included stavudine, lamivudine and indinavir (three patients), stavudine, didanosine and indinavir (four patients). KS was staged using the AIDS Clinical Trials Group classification. Patients were monitored either for a maximum of 24 weeks or until complete response or death. Tumour response was complete (absence of lesions) in five patients (71.4%) and partial (50% reduction) in two patients (28.6%). CD4 cell counts and HIV viral load (Roche Amplicor) were estimated on day 0, in week 6, and at the end of the study period. All patients exhibited a reduction in HIV viral load by week 6, although increases in CD4 cell count were negligible. All patients were seropositive for HHV-8 (immunofluorescence assay; Biotrin International Ltd., Ireland). Lymphotropic herpesviruses [cytomegalovirus (CMV), HHV-6, HHV-7, HHV-8 and Epstein–Barr virus (EBV)] were detected using a multiplex polymerase chain reaction analysis [3]. HHV-8 was detected in all tumour tissue samples. Serum and total blood were studied on day 0, weekly for the first month and fortnightly thereafter until the end of the study period. HHV-8 in the serum was detected in four patients (57%). One of each exhibited HHV-8 plus EBV and EBV plus CMV in total blood and HHV-8 in serum, indicating active replication of HHV-8, and latent EBV or CMV infection in the circulating lymphocytes. Despite the reduction in HIV viral load, HHV-8 continued to replicate actively in both cases; HHV-8 plus EBV or HHV-8 plus CMV were detected in total blood, and HHV-8 in serum, in all samples analysed up to the end of the study period. KS response to therapy by week 24 was complete in one case (patient 2, HHV plus EBV) and partial in the other (patient 5, HHV-8 plus CMV). Two patients exhibited HHV-8 viraemia in total blood and serum, indicating active replication, but no other lymphotropic herpesviruses were detected. After 2 and 4 weeks of treatment, respectively, HHV-8 viraemia disappeared, despite only a partial KS response at this time. Three patients (43%) had no HHV-8 viraemia, although in one CMV was detected in both total blood and serum. This asymptomatic patient underwent a course of intravenous ganciclovir and exhibited a virological response by week 4. Testing between weeks 4 and 24 revealed no lymphotropic herpesvirus viraemia, despite withdrawal from antiretroviral therapy. The other two patients were negative for lymphotropic herpesvirus in total blood and serum both at diagnosis and in all tests performed. Our results showed that 57% of HIV-positive patients with KS exhibited HHV-8 viraemia in the serum (see Table 1). Clearance of HHV-8 viraemia was not observed in two patients with latent EBV or CMV infection, despite HIV viral load reduction and complete/partial KS response to therapy. All findings indicated that the presence and evolution of active HHV-8 replication depends not only on tumour mass and immunosuppression, but also on other factors. One factor may be the concomitant presence of other lymphotropic viruses (EBV, CMV). EBV and HHV-8 viruses have genes with a high degree of sequential homology, and both may become latent in B lymphocytes; latent infection of B lymphocytes by EBV may facilitate persistent infection by HHV-8 [4]. In transplant patients CMV infection favours the development of EBV-associated lymphoma [5], and it may also favour HHV-8 replication in KS.Table 1: Clinical and biological response to highly active antiretroviral therapy and liposomal daunorrubicin. Julián Torre-Cisneros Francisco Pozo Raquel Serrano Elisa Vidal Antonio Rivero Antonio Tenorio