Prevalence of drug resistance mutations in HAART patients infected with HIV‐1 CRF06_cpx in Estonia

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Abstract
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.
Funding Information
  • European Regional Development Fund; Estonian Science Foundation (8004, 8415, 8856)
  • Basic Financing and the Target Financing of Estonian Ministry of Education and Research (SF0180004s12, SF0182726s06)

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