Human herpesvirus 8 cytoviraemia rebound in a patient with Kaposi's sarcoma after a short interruption of efficient antiretroviral therapy.

Abstract

In patients with Kaposi's sarcoma (KS), peripheral blood mononuclear cells (PBMC), predominately CD19 B lymphocytes, are infected with human herpesvirus 8 (HHV-8) [1]. A strong association was observed between KS disease and the levels of HHV8 DNA in PBMC, providing further evidence for a relationship between HHV-8 viral load and KS pathogenesis [2]. A decline of the incidence of KS in HIV patients has been attributed to the introduction of highly active antiretroviral therapy (HAART) [3]. Treatment with a protease inhibitor-including regimen was associated with the clearance of HHV-8 DNA in KS lesions and PBMC, and with KS lesion regression in AIDS patients [3,4]. Furthermore, a number of reports have linked tumour regression after the initiation of HAART to the restoration of immune function [5], and the immunoreconstitution to HHV-8 was suggested [6]. Recently, patients with a recurrence or development of mucocutaneous KS during viro-immunological response to HAART have been described. In these patients an intensification of HAART failed to control KS lesions [7,8]. We report here the case of an HIV-seropositive homosexual patient presenting with Pneumocystis carinii pneumonia as the AIDS-defining event in 1994. On this occasion, multiple cutaneous KS lesions were disclosed. The patient started double antiretroviral therapy and subsequently HAART in 1997, with a good viro-immunological response. He was compliant to treatment, and the KS lesions remained quiescent. No specific KS therapy was given. The patient's viro-immunological parameters are listed in Table 1.Table 1: Patient's immunological and virological parameters during therapy and at treatment interruption. The patient and medical staff agreed upon a short interruption of HAART in August 2000 because of the emergence of peripheral neuropathy. As a result of severe viro-immunological deterioration, after 10 weeks of treatment interruption, HAART was successfully reintroduced. Serum antibodies to HHV-8 lytic antigen by immunofluorescent assay and HHV-8-DNA in PBMC by qualitative polymerase chain reaction were found to be positive before HAART interruption. Otherwise, at the time of HAART interruption HHV-8 DNA in PBMC was undetectable. After one month after the reintroduction of HAART, HHV-8 DNA was again detected in PBMC and remained elevated for approximately 5 months. At the same time of the HHV-8 cytoviraemia rebound, a strong increase in the serum HHV-8 antibody titre was observed. Cutaneous KS lesions remained stable and no new lesions were observed. This case offers an indirect confirmation of the efficacy of HAART on KS. However, the clearance of HHV-8 DNA from the blood was observed after at least 17 months of HAART and was associated with immune reconstitution. The viro-immunological deterioration caused by the interruption in antiretroviral therapy was not followed by an increase in KS clinical manifestations, but HHV-8 cytoviraemia appeared again after the reintroduction of HAART and remained detectable for 5 months. The disappearance of HHV-8 cytoviraemia coincided with the control of HIV plasma viraemia and an increase in the CD4 cell count. HHV-8 DNA in peripheral mononuclear cells and antilytic antibody titre were sensitive markers of HHV-8 infection activity. In this case, the control of HHV-8 infection seemed rather to be related to immune reconstitution than to the direct activity of antiretoviral drugs on HHV-8. Because of the possibility of HHV-8 cytoviraemia rebound, the structured interruption of HAART in HHV-8-positive patients must be carefully evaluated. Saverio Giuseppe Parisia Romualdo Mazzia Loredana Sarmatib Giada Caroloa Ilaria Uccellab Alessia Riandab Emanuele Nicastric Ercola Conciaa Massimo Andreonib