Phylogenetic Analysis of Reverse Transcriptase in Antiretroviral Drug-Naive Korean HIV Type 1 Patients

Abstract

To study whether genotypic antiretroviral resistance testing (GART) is needed to guide initial antiretroviral therapy in Korea, we determined partial pol sequences in peripheral blood mononuclear cells (PBMCs) obtained from 29 antiretroviral drug-naive HIV-1 patients. Phylogenetic analysis revealed four subtypes: B (23 patients), D (1 patient), recombinant strain (2 patients), and "untyped" (3 patients). Eighteen (78.3%) of the 23 subtype B isolates formed a distinct monophyletic cluster. The average genetic distances of 23 subtype B compared with reference strain HXB2 were 2.7% (range, 1.5-4.6%). Only one patient harbored variant virus containing a V179D mutation causing resistance to efavirenz. These data derived from therapy-naive patients suggest that potential use of primary resistance testing to guide initial antiretroviral therapy should be considered in Korea. This is the first report on the molecular nature of HIV-1 RT in Korea.

Frequency of Mutations Conferring Resistance to Nucleoside Reverse Transcriptase Inhibitors in Human Immunodeficiency Virus Type 1-Infected Patients in Korea

“…Although T69N/S/D/A mutations were not detected in 29 therapy-naive patients in Korea (24), these mutations were detected in 8 patients in the present study. Therefore, our data support the notion that T69D/N/S/A may be associated not only with ddI and ddC but also with ZDV, as reported recently by Winters and Merigan (26).…”

“…Twenty-eight patients were treated with KRG for Ͼ6 months, and 4 patients (15,24,26, and 34) were treated for KRG for Ͻ6 months. The daily dose of KRG was 5.4 g. Patients were told to take six capsules (300 mg per capsule) orally three times daily (1,3,6 …”

Beneficial Effects of a Combination of Korean Red Ginseng and Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus Type 1-Infected Patients

“…3 and Table 2). Since therapy-naïve patients in Korea displayed very low rates of resistance mutations (2.3% on the protease inhibitor (PI) gene and 3.4% on the RT inhibitor gene) (29,30), we assumed that patients with no history of previous monotherapy harbored wild-type genotypes. However, one patient with baseline resistance mutations in the combination group did not display resistance mutations 3 years after HAART therapy.…”

“…Denatured DNA samples (10 l) were amplified by nested PCR. Details are described in earlier reports (29)(30)(31). The outer and inner primer pairs employed were HXB2/half RT and PO1/RIT137, The amplified products were purified and sequenced directly using the primers PO1 and RIT137 or 527.…”

Timing and evolution of the most recent common ancestor of the Korean clade HIV subtype B based on Nef and Vif sequences

“…Furthermore, majority of the HIV-1 subtype B isolated from Koreans seem to be clustered together, forming a "Korean clade" where foreign isolates are completely excluded (Kang et al, 1998). The presence of the Korean clade has been supported by further studies based on molecular phylogenetic analyses of pol (Sung et al, 2001), nef (Kang et al, 1998;Lee et al, 2003), env (Kim et al, 1999a(Kim et al, , 1999b, and vif (Park et al, 2006) genes. The Korean clade, a subcluster of HIV-1 subtype B, accounted for more than 60% of all HIV isolated from Koreans and exhibited unique nucleotide and amino acid sequences that distinguished the Korean clade from others (Park et al, 2006(Park et al, , 2008 HIV-1 is classified into three major groups, M, N, and O, and group M is further divided into several subtypes whose regional distribution is well known.…”