Sutherland, KA; Ghosn, J; Gregson, J; Mbisa, JL; Chaix, ML; Cohen Codar, I; Delfraissy, JF; ... Gupta, RK; + view all Sutherland, KA; Ghosn, J; Gregson, J; Mbisa, JL; Chaix, ML; Cohen Codar, I; Delfraissy, JF; Delaugerre, C; Gupta, RK; - view fewer (2015) HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir. Journal of Antimicrobial Chemotherapy , 70 (1) pp. 243-248. 10.1093/jac/dku365.

PDF J._Antimicrob._Chemother.-2015-Sutherland-243-8.pdf Download (245kB)

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 naïve 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 <400 copies/mL after week 24 and <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-naïve patients harbouring subtype CRF02_AG/G viruses. We speculate that this may be important in the context of suboptimal adherence in determining viral failure.

Download activity - last month

Export as JSONXMLCSV

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as JSONXMLCSV

Archive Staff Only

View Item