Emerging transmitted drug resistance in treatment-naïve human immunodeficiency virus-1 CRF06_cpx-infected patients in Estonia

Abstract

Human immunodeficiency virus (HIV)-1 transmitted drug resistance in the drug-naïve population is of growing relevance in Estonia, where the number of antiretroviral (ARV) treatment-experienced subjects has been exponentially increasing during the last 10 y. The aim of this study was to estimate the rate of transmitted drug resistance among newly diagnosed subjects in Estonia in 2008. Genotypic resistance testing for viral genomic RNA was conducted for 201 subjects tested HIV-positive between 1 April and 30 November 2008. Of 145 genotyped viral strains in newly diagnosed patients, 123 were CRF06_cpx, 2 were subtype A1 and 3 were subtype B; in 17 cases viral sequences revealed recombinant structures similar to CRF06_cpx, subtype A1 and CRF02_AG. Resistance mutations were found in 8 (5.5%) virus strains, and 3 strains were resistant to at least 2 ARV classes. A total of 2.8% of sequences harboured mutations indicating nucleoside/nucleotide reverse transcriptase inhibitor resistance (M41L, M184V, M184I, T215C and T215D), 2.1% non-nucleoside reverse transcriptase inhibitor resistance (K103N, P225H) and 2.8% protease inhibitor resistance (M46I, L90M). These data suggest the need to extend genotypic HIV-1 drug resistance testing to newly diagnosed HIV-positive subjects to prevent potential ARV treatment failure.

Transmitted Drug Resistance Is Still Low in Newly Diagnosed Human Immunodeficiency Virus Type 1 CRF06_cpx-Infected Patients in Estonia in 2010

“…9 All diagnostic and resistance testing methods in the previous and in the present study were similar. The failure rate of the resistance testing was 28% in 2008.…”

“…9 The reanalysis of sequences revealed that the TDR level was 5.5% (95% CI 1.8; 9.24). The available demographic, clinical, TDR mutation, and interpretation of data of TDR mutation-possessing subjects are presented in Table 3.…”

“…Viral RNA extraction, reverse transcription, and amplification were carried out as previously described. 9 Briefly, HIV-1 genomic RNA was extracted from 100-140 ll of serum. The reverse transcription and nested polymerase chain reaction (PCR) were performed according to a modified protocol originally developed by Dr. Jan Albert (Karolinska Institutet, Stockholm, Sweden) using the RT-PCR primer JA272degen (5¢-GGATAAATMTGACTTGCCCART-3¢), first-round PCR primers JA272degen and JA269degen (5¢-AGGAAGGMCA CARATGAARGA-3¢), followed by second-round PCR primers JA270 (5¢-GCTTCCCTCARATCACTCTT-3¢) and JA271 (5¢-CCACTAAYTTCTGTATRTCATTGAC-3¢).…”

Estonia at the Threshold of the Fourth Decade of the AIDS Era in Europe

“…53,54 Recent pol region analysis showed that the subtype structure of the Estonian HIV epidemic remained unchanged up to 2008. [56][57][58] Drug resistance mutations of HIV were investigated in Estonian treatment naive populations in 2005-2006 and 2008. [56][57][58] These studies indicated that CRF06_cpx and its recombinant forms with subtypes A1 possess several naturally occurring polymorphisms in the protease region (K14R, M36I, H69K, and L89M), also characteristic to other non-B subtype epidemics.…”

“…58 Yet a rapid increase to a 5.5% prevalence of these mutations was detected in samples collected from newly diagnosed HIV patients in 2008--in eight samples drug resistance mutations to the three most widely used antiretroviral drug classes (PI, NNRTI, and NRTI) were detected and three strains possessed mutations determining resistance to at least two antiretroviral classes. 58 These results are slightly above the threshold considered critical for implementation of pretreatment drug resistance testing according to the ''Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents.'' 59 A third integrase region genotyping study has detected several drug resistance-associated polymorphisms (V72I, L74I, V201I, and T206S), but no primary drug resistance mutations against integrase inhibitors.…”