Characterization of HIV‐1 subtypes and drug resistance mutations among individuals infected with HIV in Georgia

Abstract

In order to describe HIV-1 subtypes and drug resistance mutations in Georgia, blood samples from 153 patients infected with HIV-1 collected from 2006 to 2008 were genotyped. Of these, 126 samples were from newly diagnosed, antiretroviral (ARV)-naïve patients and 27 from ARV-treated patients. Partial pol region sequences were used to identify drug resistance mutations and to conduct phylogenetic analysis for subtype determination. The results indicated that 138 (90.2%) patients harbored subtype A viruses, 11 (7.2%) carried subtype B virus, two subtype G (1.3%), one (0.6%) subtype F and one (0.6%) 03_AB recombinant. All subtype A strains clustered with the Former Soviet Union A (A FSU) subtype. Among patients with no prior exposure to ARVs, mutations associated with resistance were detected in five patients: three (2.4%) patients had reverse transcriptase (RT) inhibitor mutations and two other patients had the protease (PI) inhibitor associated mutation M46I. PI mutation V77I was found in 42 of subtype A isolates. Of 27 ARV-treated patients, 22 (81.5%) harbored at least one nucleoside reverse transcriptase inhibitors (NRTI), a non-NRTI (NNRTI) and/or a PI mutation. The most common NRTI resistance mutation was M184V/I (74.1%). Frequency of thymidine analog mutations was relatively low (25.9%). With regard to NNRTI mutations, G190S/A was the most frequent mutation, which might be a preferred mutations for subtype A. Georgia's HIV epidemic continues to be dominated by Subtype A FSU. The prevalence of transmitted drug resistance is low, but has the potential to increase with increasing use of ARVs.

A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses

“…The most common NNRTI-resistance mutations in 725 samples from 647 NNRTI-experienced patients with subtype A viruses were K103N (19%), G190A (13%), Y181C (11%), K101E (4.4%), G190S (3.9%), and Y188L (1.7%) (Supplemental Figure 1, http://links.lww.com/QAD/A586). Of 25 patients with G190S, 16 (35%) were from two studies of 46 patients from FSU countries [17,18] compared with 9 (1.5%) of 601 patients from the remaining studies ( P < 0.001). G190S was not identified in more than 3000 antiretroviral-naive patients with subtype A viruses including more than 700 patients in FSU countries.…”

HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia

“…The A62V RT alone is rare in subtype B, TN-samples as it reduces the replication capacity of these variants to 50% compared to the wild type (wt) virus [37]. In A6 samples, A62V RT is an endemic polymorphism with similarly high prevalence among TN and TE patients [9,38,39]. These prevalence trends strongly suggest that this mutation probably does not lead to a sharp reduction of replication capacity in the context of sub-subtype A6, though no experimental data to confirm this hypothesis are available yet.…”

“…In non-A6 isolates, K103N RT or Y181C RT are preferentially detected after efavirenz exposure [40][41][42][43] while G190S RT is rarely observed, probably due to high costs in replication capacity (in the subtype B context, 20% compared to the wt) [41]. Conversely, G190S development in A6 isolates is significantly higher (up to 30% to 60%) after EFV and/or nevirapine (NVP)-exposure and is favoured over the K103N and Y181C resistance pathways [10,38,39,[42][43][44]. These subtype differences may be partially attributable to the nucleotide exchanges required to achieve the amino acid substitution: While one transition and one transversion (GGA to TCA or AGY) are required in non-A6 isolates, only one transition is required (GGC to AGC) in the A6 genetic background [42].…”

The Prevalence of Hiv Recombinant Forms in Russia and Countries of the Cis: Systematic Review and Metaanalysis

“…Закавказскую подгруппу стран СНГ (табл.) составили два исследования [23,32]. Обобщенная распространенность рекомбинантных форм ВИЧ составила 1,6% (95% ДИ 1,3-4,4) и характеризовалась умеренной гетерогенностью (I 2 = 49,2%, p = 0,160; рис.…”