Ition to AGA, explaining why arginine is present at a higherItion to AGA, explaining why

Ition to AGA, explaining why arginine is present at a higher
Ition to AGA, explaining why arginine is present at a higher frequency in non-B subtypes [34]. Many of the secondary resistance mutations listed in Tables 1, 2, 3, 4 and 9 occur at positions that are considered polymorphic, i.e. dependent on subtype and geographical distribution; this complicates the nature of the selection of these polymorphic changes as a function of INSTI exposure. Any description of transmitted INSTI drug resistance (for a review of the effect of subtype diversity and polymorphisms on HIV-1 INSTI resistance see [37]) must also be thereby complicated. A more accurate portrait of patterns of second-generation INSTI resistance mutations in non-B subtypes, which is increasingly EPZ004777 custom synthesis important as access to these medications increases in developing countries, will require that selection studies be conducted more frequently with non-B primary isolates [90]. The Q148 pathway remains the dominant route to INSTI resistance, regardless of the individual compound used. All second-generation INSTIs show lower activity against PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27663262 HIV as secondary mutations of this pathway accumulate, and the results of INSTI-experienced patients on DTG therapy suggest that once present, the sequential selection of further mutations in this pathway will result in greatly diminished susceptibilities to this compound (Table 9; see also [86]). Even though the Q148 substitutions may not be selected by either DTG or BIC in vivo, they remain important for the future of these compounds. Predictions of which pathways will be important for resistance to second-generation INSTIs, unlike first-generation INSTIs, may not easily follow from in vitro studies. If resistance to these compounds turns out to be due to random genetic changes that are not easily identified, genotyping of patient-derived viruses may not be able to predict treatment outcome when these compounds are employed [37, 86]. Perhaps, the high genetic barrier to resistance of DTG will force HIV to evolve along different mutational pathways in vitro versus in vivo, depending on subtype and baseline polymorphisms.Authors’ contributions KA performed the literature review, prepared the tables, and wrote the first draft of the manuscript, all under the guidance of TM. BB, TM and MAW reviewed and edited the manuscript. All authors read and approved the final manuscript.Anstett et al. Retrovirology (2017) 14:Page 14 ofAuthor details 1 Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montreal, QC, Canada. 2 McGill AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote-Ste-Catherine Road, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/26437915 Montreal, QC, Canada. Acknowledgements This review is dedicated to the memory of Dr. Mark Wainberg, our friend and mentor, whose dedication to the cause of those affected by HIV will continue to inspire us and elicit our admiration. Competing interests The authors declare that they have no competing interests. Availability of data and materials Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. Funding MAW was supported by grants from the Canadian Institutes of Health Research (CIHR). KA is the recipient of a doctoral studentship from CIHR.15.16. 17.18. 19.20.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Received: 15 May 2017 Accepted: 30 May 2017 21. 22.References 1. World Health Organisation t. HIV/AIDS.