Protease sequences from HIV-1 group M subtypes A-H reveal distinct amino acid mutation patterns associated with protease resistance in protease inhibitor-naive individuals worldwide

Citation
D. Pieniazek et al., Protease sequences from HIV-1 group M subtypes A-H reveal distinct amino acid mutation patterns associated with protease resistance in protease inhibitor-naive individuals worldwide, AIDS, 14(11), 2000, pp. 1489-1495
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
AIDS
ISSN journal
0269-9370 → ACNP
Volume
14
Issue
11
Year of publication
2000
Pages
1489 - 1495
Database
ISI
SICI code
0269-9370(20000728)14:11<1489:PSFHGM>2.0.ZU;2-N
Abstract
Background: Although numerous mutations that confer resistance to protease inhibitors (PRI) have been mapped for HIV-1 subtype B, little is known abou t such substitutions for the non-B viruses, which globally cause the most i nfections. Objectives: To determine the prevalence of PRI-associated mutations in PRI- naive individuals worldwide. Design: Using the polymerase chain reaction, protease sequences were amplif ied from 301 individuals infected with HIV-1 subtypes A (79), 8 (95), B' (1 9), C (12), D (26), A/E (23), F (26), A/G (11), and H (3) and unclassifiabl e HIV-1 (7). Amplified DNA was directly sequenced and translated to amino a cids to analyze PRI-associated major and accessory mutations. Results: Of the 301 sequences, 85% contained at least one codon change givi ng substitution at 10, 20, 30, 36, 46, 63, 71, 77, or 82 associated with PR I resistance; the frequency of these substitutions was higher among non-B ( 91%) than B (75%) viruses (P < 0.0005). Of these, 25% carried dual and trip le substitutions. Two major drug resistance-conferring mutations, either 20 M or 30N, were identified in only three specimens, whereas drug. resistance accessory mutations were found in 252 isolates. These mutations gave disti nct prevalence patterns for subtype B, 63P (62%) > 771 (19%) > 101/V/R (6%) = 361 (6%) = 71T/V (6%) > 20R (2%), and non-B strains, 361 (83%) > 63P (17 %) > 10/V/R (13%) > 20R(10%) > 771 (2%), which differed statistically at po sitions 20, 36, 63, 71, and 77. Conclusions: The high prevalence of PRI-associated substitutions represent natural polymorphisms occurring in PRI-naive patients infected with HIV-1 s trains of subtypes A-H. The significance of distinct mutation patterns iden tified for subtype B and non-B strains warrants further clinical evaluation . A global HIV-1 protease database is fundamental for the investigation of novel PRI. (C) 2000 Lippincott Williams & Wilkins.