Title: Structural modifications induced by specific HIV-1 protease-compensatory mutations have an impact on the virological response to a first-line lopinavir/ritonavir-containing regimen
Authors: Alteri, Claudia ×
Artese, Anna
Beheydt, Gertjan
Santoro, Maria Mercedes
Costa, Giosuè
Parrotta, Lucia
Bertoli, Ada
Gori, Caterina
Orchi, Nicoletta
Girardi, Enrico
Antinori, Andrea
Alcaro, Stefano
d'Arminio Monforte, Antonella
Theys, Kristof
Vandamme, Anne-Mieke
Ceccherini-Silberstein, Francesca
Svicher, Valentina
Perno, Carlo Federico #
Issue Date: Oct-2013
Publisher: Oxford University Press
Series Title: The Journal of Antimicrobial Chemotherapy vol:68 issue:10 pages:2205-2209
Abstract: OBJECTIVES: This study evaluates the impact of specific HIV-1 protease-compensatory mutations (wild-type amino acids in non-B subtypes) on virological response to a first-line lopinavir/ritonavir-containing regimen in an HIV-1 subtype B-infected population. PATIENTS AND METHODS: The prevalence of protease-compensatory mutations from 1997 to 2011 was calculated in 3063 drug-naive HIV-1 B-infected patients. The role of these mutations on virological outcome is estimated in a subgroup of 201 patients starting their first lopinavir/ritonavir-containing regimen by covariation and docking analyses. RESULTS: The number of HIV-1 B-infected patients with at least one protease-compensatory mutation increased over time (from 86.4% prior to 2001 to 92.6% after 2009, P = 0.02). Analysing 201 patients starting first-line lopinavir/ritonavir, the median time to virological failure was shorter in patients with at least one protease-compensatory mutation than in patients with no protease-compensatory mutations. By covariation and docking analyses, specific mutations were found to affect lopinavir affinity for HIV-1 protease and to impact virological failure. Specifically, the L10V + I13V + L63P + I93L cluster, related to fast virological failure, correlated with a decreased drug affinity for the enzyme in comparison with wild-type (ΔGmut = -30.0 kcal/mol versus ΔGwt = -42.3 kcal/mol). CONCLUSIONS: Our study shows an increased prevalence of specific protease-compensatory mutations in an HIV-1 B-infected population and confirms that their copresence can affect the virological outcome in patients starting a lopinavir/ritonavir-containing regimen.
ISSN: 0305-7453
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Clinical and Epidemiological Virology (Rega Institute)
× corresponding author
# (joint) last author

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