AEGiS-14IAC: Polymorphism of protease in protease inhibitor (PI)-naïve patients.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Polymorphism of protease in protease inhibitor (PI)-naïve patients.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. B10204)

Cho Y, Ahn S, Kang M, Sung H
University of Ulsan College of Medicine, SEOUL, Republic of Korea

BACKGROUND: There is no report on natural polymorphism of protease (PRO) from PI-naïve patients in Korea although we have reported on the frequency of resistance mutation to reverse transcriptase inhibitors (J Clin. Microbiolol, in press) and natural polymorphism (AIDS Res & Hum Retroviruses. 16:1549-, 2001). The distribution of subtype was 79%, 10%, 7%, and 3% for subtype B, "untyped", recombinant, and D, respectively. The information on natural polymorphism of HIV-1 PRO in a certain region is needed to determine whether resistance mutation developed after introduction of PI regimen.

METHODS: We determined 44 PRO sequences from 40 PI naïve persons diagnosed before 1994. A nested polymerase chain reaction and direct sequencing methods were used to define PRO in DNA from peripheral blood mononuclear cell samples.

RESULTS: Although all the patients had resistance mutation (T20, A9, P8, S3, M2) at codon 63, we could not find intrapersonal variation at 63. The second most common mutation was at codon 37 (S35, D2, A1, and C1). The frequency of resistance mutation was as follows; I93L, V77I, I15V, A71T, L10I, M36I, and L90M were 14 (35%), 13(30%), 11(28%), 6(14%), 4(9%), 2(5%), and 1(2%), respectively. The number of persons with resistance mutations of 6, 5, 4, 3, 2, and 1 were 1, 5, 11, 14, 5 and 2, respectively. Irrespective of resistance, the frequency of I72T/V and T12P/I/K/A/S were 12 (30%) and 7(18%), respectively. One patient showed a gross deletion (257 bp) from codon 91 to reverse transcriptase.

CONCLUSIONS: Polymorphism has been observed in25 of the 99 amino acids. Use of primary resistance testing to guide initial PI therapy shoud be considered in Korea.

Keywords: AEGIS, Protease Inhibitors, HIV-1, HIV Protease, Endopeptidases, Reverse Transcriptase Inhibitors, Polymorphism (Genetics), HIV-1 Reverse Transcriptase, HIV Protease Inhibitors, Mutation, Variation (Genetics), Codon, RNA-Directed DNA Polymerase, Korea, Human, genetics

020707
B10204