Previous Article | Next Article ![]()
Journal of Clinical Microbiology, November 2000, p. 3919-3925, Vol. 38, No. 11
Laboratoire Retrovirus, IRD,
Montpellier,1 CHU, Caremeau, 30029 Nimes
cedex 4,5 and CHU, Gui de Chauliac,
34295 Montpellier Cedex 5,6 France;
Projet PRESICA, BP 906, Yaounde,
Cameroon2; CHU, Le Dantec, BP 7325, Dakar, Senegal3; and Innogenetics, 9052 Zwijnaarde, Belgium4
Received 24 February 2000/Returned for modification 11 May
2000/Accepted 17 July 2000
Most human immunodeficiency virus (HIV) drug susceptibility studies
have involved subtype B strains. Little information on the impact of
viral diversity on natural susceptibility to antiretroviral drugs has
been reported. However, the prevalence of non-subtype-B (non-B) HIV
type 1 (HIV-1) strains continues to increase in industrialized countries, and antiretroviral treatments have recently become available
in certain developing countries where non-B subtypes predominate. We
sequenced the protease and reverse transcriptase (RT) genes of 142 HIV-1 isolates from antiretroviral-naive patients: 4 belonged to group
O and 138 belonged to group M (9 subtype A, 13 subtype B, 2 subtype C,
5 subtype D, 2 subtype F1, 9 subtype F2, 4 subtype G, 5 subtype J, 2 subtype K, 3 subtype CRF01-AE, 67 subtype CRF02-AG, and 17 unclassified
isolates). No major mutations associated with resistance to nucleoside
reverse transcriptase inhibitors (NRTIs) or protease inhibitors were
detected. Major mutations linked to resistance to non-NRTI agents were
detected in all group O isolates (A98G and Y181C) and in one subtype J virus (V108I). In contrast, many accessory mutations were found, especially in the protease gene. Only 5.6% of the 142 strains, all
belonging to subtype B or D, had no mutations in the protease gene.
Sixty percent had one mutation, 22.5% had two mutations, 9.8% had
three mutations, and 2.1% (all group O strains) had four mutations. In
order of decreasing frequency, the following mutations were identified
in the protease gene: M36I (86.6%), L10I/V (26%), L63P (12.6%),
K20M/R (11.2%), V77I (5.6%), A71V (2.8%), L33F (0.7%), and M46I
(0.7%). R211K, an accessory mutation associated with NRTI resistance,
was also observed in 43.6% of the samples. Phenotypic and clinical
studies are now required to determine whether multidrug-resistant viruses emerge more rapidly during antiretroviral therapy when minor
resistance-conferring mutations are present before treatment initiation.
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Genetic Diversity of Protease and Reverse
Transcriptase Sequences in Non-Subtype-B Human Immunodeficiency Virus
Type 1 Strains: Evidence of Many Minor Drug Resistance Mutations in
Treatment-Naive Patients
*
Corresponding author. Mailing address: Laboratoire
Retrovirus, IRD, 911 Avenue Agropolis, BP 5045, 34032 Montpellier Cedex 1, France. Phone: 33-4 67 41 62 97. Fax: 33-4 67 61 94 50. E-mail: martine.peeters{at}mpl.ird.fr.
This article has been cited by other articles:
| Antimicrob. Agents Chemother. | Clin. Microbiol. Rev. |
|---|---|
| Clin. Vaccine Immunol. | ALL ASM JOURNALS |
|---|