Antiretroviral Therapy in HTLV-1 Infection: An Updated Overview

Abstract

The human T cell leukemic/lymphotropic virus type 1 (HTLV-1), discovered several years ago, is the causative agent for a rapid progressive haematological malignancy, adult T cell leukemia (ATL), for debilitating neurological diseases and for a number of inflammatory based diseases. Although the heterogeneous features of the diseases caused by HTLV-1, a common topic concerning related therapeutic treatments relies on the use of antiretrovirals. This review will compare the different approaches and opinions in this matter, giving a concise overview of preclinical as well as clinical studies covering all the aspects of antiretrovirals in HTLV-1 infection. Studies will be grouped on the basis of the class of antiretroviral, putting together both pre-clinical and clinical results and generally following a chronological order. Analysis of the existing literature highlights that a number of preclinical studies clearly demonstrate that different classes of antiretrovirals, already utilized as anti-HIV agents, are actually capable to efficiently contrast HTLV-1 infection. Nevertheless, the results of most of the clinical studies are generally discouraging on the same point. In conclusion, the design of new antiretrovirals more specifically focused on HTLV-1 targets, and/or the establishment of early treatments with antiretrovirals could hopefully change the perspectives of diseases caused by HTLV-1.

Keywords: ATL; HAM/TSP; HTLV-1; antiretrovirals.

Figure 1

Schematic representation of HTLV-1 transmission and possible mechanisms of antiviral therapy. (a) Process by which nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs) interrupt the horizontal cell-to-cell transmission of HTLV-1 from an infected cell to an uninfected cell. (b) Processes by which NRTIs, INSTIs and ritonavir could interfere with the vertical transmission of HTLV-1 and consequent insurgence of diseases: this could occur by interrupting the transmission of the virus from infected clones to uninfected cells and by limiting clonal expansion through induction of apoptosis, in combination or not with other compounds. * Note that, among the other NRTIs, AZT has been proved to effectively interrupt the maintaining route of ATL in combination with IFNa, at least transiently.