@article{discovery1443549, number = {1}, title = {HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir}, year = {2015}, volume = {70}, pages = {243--248}, journal = {Journal of Antimicrobial Chemotherapy}, publisher = {Oxford University Press}, note = {{\copyright} The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.}, abstract = {Objective: PI susceptibility results from a complex interplay between Protease and Gag proteins, with Gag showing wide variation across HIV-1-subtypes. We explored the impact of pre-treatment susceptibility on the outcome to lopinavir/ritonavir (LPV/r) monotherapy. Methods: Treatment na{\"i}ve individuals who experienced LPV/r monotherapy failure from the MONARK study were matched (by subtype, viral load and baseline CD4 count) to those who achieved virological response ('successes'). Successes were defined by viral load {\ensuremath{<}}400 copies/mL after week 24 and {\ensuremath{<}}50 copies/mL from week 48 to 96. Full-length Gag-protease was amplified from patient samples for in vitro phenotypic susceptibility testing, with susceptibility expressed as fold change (FC) relative to a subtype B reference strain. Results: Baseline LPV susceptibility was lower in viral failures compared to viral successes, but the differences were not statistically significant (median LPV susceptibility: 4.4 vs 8.5 respectively, p=0.17. Amongst CRF02\_AG/G patients, there was a significant difference in LPV susceptibility between the two groups (median LPV susceptibility: 7.1 vs 10.4 respectively, p=0.047), while in subtype B the difference was not significant (2.7 vs 3.4, p=0.13). Subtype CRF02\_AG /G viruses had a median LPV FC of 8.7, compared to 3.1 for subtype B (p=0.001). Conclusions: We report an association between reduced PI susceptibility (using full-length Gag-protease sequences) at baseline and subsequent virological failure on LPV/r monotherapy in ARV-na{\"i}ve patients harbouring subtype CRF02\_AG/G viruses. We speculate that this may be important in the context of suboptimal adherence in determining viral failure.}, author = {Sutherland, KA and Ghosn, J and Gregson, J and Mbisa, JL and Chaix, ML and Cohen Codar, I and Delfraissy, JF and Delaugerre, C and Gupta, RK}, url = {http://dx.doi.org/10.1093/jac/dku365}, issn = {1460-2091}, keywords = {HIV, antiretroviral therapy, resistance, protease inhibitor, gag} }