Quantification of HTLV-1 reverse transcriptase activity in ATL patients treated with zidovudine and interferon-a

The human T-lymphotropic virus type 1 (HTLV-1) retrovirus1 is the etiological agent of adult T-cell leukemia/lymphoma (ATL), HTLV-1-associated myelopathy/tropical spastic paraparesis, and a number of inflammatory diseases.2 ATL is an aggressive malignancy occurring mostly in adults 30 to 50 years after HTLV-1 infection. ATL cells are characterized by low virus expression in vivo. The prognosis is very poor, ranging from 6 to 24 months median survival. Chemotherapy has little long-term efficacy in ATL. Allogeneic stem cell transplantation can result in long-term disease control but few patients can be successfully transplanted.3 Antiretrovirals with activity against HIV-1, such as zidovudine (39-azido-29,39-dideoxythymidine [AZT]) and tenofovir, and new phosphonated compounds, efficiently block HTLV-1 transmission in vitro,4-7 whereas HTLV-1 was resistant to lamivudine.Two preliminary phase 2 studies using the combination of AZT and interferon-a (IFN-a) reported an unexpectedly high response rate, particularly in previously untreated acute ATL patients.9-11 The efficacy of this combination was confirmed, with minor differences, in various clinical trials and in a worldwide meta-analysis.12-16 These results changed the clinical management of ATL.16-19 However, there is yet no direct proof of an antiviral mechanism of action of the drug combination, due to the absence of virological markers that strictly correlate with disease status. In this study, we investigated HTLV-1 reverse transcriptase (RT) activity and other virological parameters, in samples from short-term cultures of peripheral blood mononuclear cells (PBMCs) collected from ATL patients before and after therapy.