title: Susceptibility of primary HTLV-1 isolates from patients with HTLV-1-associated myelopathy to reverse transcriptase inhibitors.
abstract: Since human T-lymphotropic virus type 1 (HTLV-1)-associated diseases are associated with a high HTLV-1 load, reducing this load may treat or prevent disease. However, despite in vitro evidence that certain nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs) are active against HTLV-1, in vivo results have been disappointing. We therefore assayed the sensitivity of HTLV-1 primary isolates to a panel of RT inhibitors. HTLV-1 primary isolates were obtained, pre- and post- NRTI treatment, from patients with HTLV-1-associated myelopathy. Sensitivity to azidothymidine (AZT), lamivudine (3TC), tenofovir (TDF) and three phosphonated carbocyclic 2'-oxa-3'aza nucleosides (PCOANs) was assessed in a RT inhibitor assay. With the exception of 3TC, HTLV RT from primary isolates was less sensitive to all tested inhibitors than HTLV-1 RT from MT-2 cells. HTLV-1 RT from primary isolates and from chronically infected, transformed MT-2 cells was insensitive to 3TC. Sensitivity of primary isolates to RT inhibitors was not reduced following up to 12 months of patient treatment with AZT plus 3TC. The sensitivity of HTLV-1 primary isolates to NRTIs differs from that of cell lines and may vary among patients. Failure of NRTIs to reduce HTLV-1 viral load in vivo was not due to the development of phenotypic NRTI resistance. AZT and the three PCOANs assayed all consistently inhibited primary isolate HTLV-1 RT.
authors: Department of Neuroscience, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Beatrice
authors: B
authors: Macchi
authors: Emanuela
authors: E
authors: Balestrieri
authors: Arianna
authors: A
authors: Ascolani
authors: Silva
authors: S
authors: Hilburn
authors: Fabiola
authors: F
authors: Martin
authors: Antonio
authors: A
authors: Mastino
authors: Graham P
authors: GP
authors: Taylor
mesh_terms: D000328:Adult; D002460:Cell Line; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000821:virology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D018894:Reverse Transcriptase Inhibitors