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Prevalence of drug resistance mutations in HAART patients infected with HIV‐1 CRF06_cpx in Estonia
Author(s) -
Avi Radko,
Pauskar Merit,
Karki Tõnis,
Kallas Eveli,
Jõgeda EneLy,
Margus Tõnu,
Huik Kristi,
Lutsar Irja
Publication year - 2016
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.24361
Subject(s) - virology , efavirenz , zidovudine , abacavir , resistance mutation , lamivudine , didanosine , reverse transcriptase inhibitor , population , reverse transcriptase , drug resistance , biology , nucleoside reverse transcriptase inhibitor , medicine , viral load , virus , antiretroviral therapy , viral disease , genetics , polymerase chain reaction , hepatitis b virus , environmental health , gene
HIV‐1 drug resistance mutations (DRMs) and substitutions were assessed after the failure of the first line non‐nucleoside reverse transcriptase inhibitors (NNRTIs) + 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) treatment regimens (efavirenz [EFV] + lamivudine[3TC] + zidovudine [ZDV] vs. EFV + 3TC + ddI) among the HIV‐1 CRF06_cpx infected subjects in Estonia. HIV‐1 genomic RNA was sequenced; DRMs and amino acid substitutions were compared in 44 treatment naïve and 45 first‐line NNRTI + 2 NRTI treatment failed patients consisting of EFV + 3TC + ZDV ( n = 17) and EFV + 3TC + didanosine[ddI] ( n = 21) therapy failed sub‐populations. At least one DRM was found in 78% of treatment experienced patients. The most common NRTI mutations were M184V (80%), L74V (31%), L74I (17%), K219E (9%), and M184I (9%), NNRTI mutations were K103N (83%), P225H (14%), L100I (11%), and Y188L (11%), reflecting generally the similar pattern of DRMs to that seen in treatment failed subtype B viruses. Sub‐population analysis revealed that EFV + 3TC + ddI failed patients had more DRMs compared to EFV + 3TC + ZDV failed patients, especially the ddI DRM L74IV and several additional NNRTI DRMs. Additionally, CRF06_cpx specific mutation E179V and substitutions R32K, K122E, and V200AE were also detected in treatment experienced population. After the failure of the first‐line EFV + 3TC + ddI therapy HIV‐1 CRF06_cpx viruses develop additional NRTI and NNRTI mutations compared to EFV + 3TC + ZDV regimen. Therefore the usage of EFV + 3TC + ddI in this subtype decreases the options for next regimens containing abacavir, and NNRTI class agents. J. Med. Virol. 88:???–???, 2016 . © 2015 Wiley Periodicals, Inc.