Prevalence of drug resistance mutations in HAART patients infected with HIV-1 CRF06_cpx in Estonia.
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.
Department of Microbiology, Faculty of Medicine, University of Tartu, Tartu, Estonia.
Radko
R
Avi
Department of Microbiology, Faculty of Medicine, University of Tartu, Tartu, Estonia.
Merit
M
Pauskar
Department of Microbiology, Faculty of Medicine, University of Tartu, Tartu, Estonia.
Tõnis
T
Karki
Department of Microbiology, Faculty of Medicine, University of Tartu, Tartu, Estonia.
Eveli
E
Kallas
Department of Microbiology, Faculty of Medicine, University of Tartu, Tartu, Estonia.
Ene-Ly
EL
Jõgeda
Department of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Tõnu
T
Margus
Department of Microbiology, Faculty of Medicine, University of Tartu, Tartu, Estonia.
Kristi
K
Huik
Department of Microbiology, Faculty of Medicine, University of Tartu, Tartu, Estonia.
Irja
I
Lutsar
D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000627:therapeutic use; D003521:Cyclopropanes; D016049:Didanosine / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D004957:Estonia / Q000453:epidemiology; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use; D000099227:Abacavir
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D016049:Didanosine; D015224:Dideoxynucleosides; D019259:Lamivudine; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D000099227:Abacavir; C098320:efavirenz
CRF06_cpx; drug resistance; injecting drug use; monophyletic; subtype specific pathways