Abstract
BackgroundMulti-nucleos(t)ide resistance (MNR) mutations including Q151M, K65R mutations, and insertion at codon 69 of HIV-1 reverse transcriptase coding region may confer resistance to all molecules of nucleos(t)ide reverse transcriptase inhibitors (NRTI). The presence of these mutations is an emerging problem compromising non-nucleoside reverse transcriptase inhibitors and protease inhibitors-based therapies. Furthermore, factors associated with selection of these mutations are still not well defined. The current study aimed to evaluate the frequency and to characterize factors associated with the occurrence of multi-nucleos(t)ide resistance mutations among HIV-1 infected patients failing recommended first-line antiretroviral regimens in Cambodia.Methodology/Principal FindingThis is a retrospective analysis of HIV-1 drug resistance genotyping of 520 HIV-1 infected patients in virological failure (viral load > 250 copies/mL) while on first-line antiretroviral therapy in Cambodia with at least one reverse transcriptase inhibitor resistance associated mutation. Among these 520 patients, a total of 66 subjects (66/520, 12.7%) presented ≥1 MNR mutation, including Q151M, K65R, and Insert69 for 59 (11.3%), 29 (5.6%), and 2 (0.4%) patients, respectively. In multivariate analysis, both Q151M (p = 0.039) and K65R (p = 0.029) mutations were independently associated with current stavudine- compared to zidovudine-use.ConclusionSuch selection of mutations by stavudine drastically limits the choice of antiretroviral molecules available for second-line therapy in resource-limited settings. This finding supports the World Health Organization’s recommendation for stavudine phase-out.
Highlights
Q151M, K65R substitutions, and insertions at codon 69 (Insert69) in the reverse transcriptase encoding region of HIV-1 genome confer resistance to a large range of nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and are called multinucleos(t)ide resistance (MNR) mutations
Our study aimed to evaluate the frequency and to identify factors associated with the occurrence of Multi-nucleos(t)ide resistance (MNR) mutations among HIV-1 CRF01_AE infected patients failing recommended first-line Highly Active Antiretroviral Therapy (HAART) in Cambodia
520 subjects infected with HIV-1 CRF01_AE strains and presenting at least one RTI resistance associated mutation (RAM) were included in this analysis
Summary
Q151M, K65R substitutions, and insertions at codon 69 (Insert69) in the reverse transcriptase encoding region of HIV-1 genome confer resistance to a large range of nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and are called multinucleos(t)ide resistance (MNR) mutations. K65R confers resistance to stavudine (d4T) and TDF and possibly to lamivudine/emtricitabine (3TC/FTC), didanosine (ddI) and abacavir (ABC) [2,3,4,5], while Insert confers resistance to all NRTIs available today [6,7,8] These mutations dramatically compromise subsequent antiretroviral (ARV) regimens. D4T/ddI dual therapy has been associated with the occurrence of Q151M and K65R [9,10,11], as well as young age, low CD4+ T-cell count, high HIV RNA viral load (VL) and experience of more than two ARV regimens before resistance genotyping testing [12,13] These studies mostly enrolled patients under dual therapies. Our study aimed to evaluate the frequency and to identify factors associated with the occurrence of MNR mutations among HIV-1 CRF01_AE infected patients failing recommended first-line HAART in Cambodia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
