Susceptibility of human T cell leukemia virus type 1 to reverse-transcriptase inhibitors: evidence for resistance to lamivudine.
Nucleoside reverse-transcriptase (RT) inhibitors (NRTIs), including lamivudine (3TC) and zidovudine (Zdv), are being evaluated for the treatment of human T cell lymphotropic virus type 1 (HTLV-1)-associated disease. However, information on the susceptibility of HTLV-1 to these drugs is limited. The activity of 5 NRTIs on HTLV-1 RT was evaluated. IC(50) values for Zdv, zalcitabine (ddC), didanosine (ddI), 3TC, and stavudine (d4T) were determined, using an enzymatic assay, for 5 HTLV-1 isolates and for reference wild-type and NRTI-resistant human immunodeficiency virus type 1 (HIV-1). Both HTLV-1 and wild-type HIV-1 were equally susceptible to Zdv, ddC, ddI, and d4T. In contrast, high-level resistance to 3TC was found in all HTLV-1 isolates. The findings support the clinical use of Zdv, ddC, ddI, and d4T but not of 3TC for the antiretroviral treatment of HTLV-1-associated disease.
García-Lerma
J G
JG
HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA. jng5@cdc.gov
Nidtha
S
S
Heneine
W
W
D000595:Amino Acid Sequence; D006800:Deltaretrovirus Infections / Q000821:virology; D004352:Drug Resistance, Microbial; D015658:HIV Infections / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000379:methods; D008969:Molecular Sequence Data; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase