title: Mutation patterns of the reverse transcriptase genes in HIV-1 infected patients receiving combinations of nucleoside and non nucleoside inhibitors.
abstract: A genotyping assay was used to define human immunodeficiency virus type 1 (HIV-1) reverse transcriptase codons in plasma samples from 80 HIV-1 patients extensively treated with two nucleoside reverse transcriptase (zidovudine and lamivudine) and one non nucleoside reverse transcriptase (nevirapine) inhibitor. The frequencies of T215S/Y/F, M41L, D67N, L210W K70R, K219Q mutations, detectable in plasma samples, conferring resistance to zidovudine were 61.2, 56.2, 36.2, 31.5, 27.5 and 17.5%, respectively. Mutations (M184V or M184I) conferring resistance to lamivudine were detected in an extremely high percentage of patients (61%). Among mutations correlated to high (K103N, V106A, Y181C/I, Y188C/H/L, G190A/C/E/Q/S/T) or moderate (V108I, V118I) levels of nevirapine resistance, the predominant amino acid change was a substitution at 103 codon, present in 24 of 80 samples tested. Finally Q151M, the marker mutation able to confer resistance to all nucleoside analogues, was detected in seven patients with a viral load of between 1 x 10(4) and 9 x 10(4) HIV-1 RNA copies/ml. The relationship between the genotype and the viral load showed that the incidence of some specific mutations [M41L, T215Y (correlated to zidovudine resistance) and K103N (correlated to all NNRTIs drugs)] significantly (P=0.001) increased with higher viral load. Our results, albeit limited to a small cohort, showed a high frequency of mutations correlated to drugs in use, suggesting a need for therapeutic change in the near future and demonstrating that the development of genotyping tests helps to guide the therapeutic management of HIV-1 infected people. Our data highlight the dangers of selecting antiretroviral therapy without previous antiretroviral drug testing. Although the cost of these assays is a concern, prescribing inefficacious drugs could create serious problems for HIV-1 patients.
authors.affiliation: Section of Microbiology, Department of Clinical and Experimental Medicine, University of Bologna, St. Orsola Hospital, Via Massarenti 9, 40138 Bologna, Italy. remc@med.unibo.it
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Re
authors.forename: I
authors.initials: I
authors.lastname: Bon
authors.forename: P
authors.initials: P
authors.lastname: Monari
authors.forename: M
authors.initials: M
authors.lastname: Borderi
authors.forename: D
authors.initials: D
authors.lastname: Gibellini
authors.forename: P
authors.initials: P
authors.lastname: Schiavone
authors.forename: F
authors.initials: F
authors.lastname: Vitone
authors.forename: F
authors.initials: F
authors.lastname: Chiodo
authors.forename: M
authors.initials: M
authors.lastname: La Placa
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005838:Genotype; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000235:genetics; D006801:Humans; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase