Prevalence of primary resistance mutations to integrase inhibitors in treatment-naïve and -experienced patients infected with B and non-B HIV-1 variants.
BACKGROUND
Raltegravir (RAL) constitutes the first available integrase strand transfer inhibitor (INSTI) available in clinical practice. Three independent pathways have been described to confer resistance to RAL. Secondary mutations with little effect on INSTI susceptibility and additional substitutions with an uncertain role have also been described especially in HIV-1 non-B variants.


METHODS
We evaluated the prevalence of primary, secondary, and additional resistance mutations to INSTIs in patients naïve to RAL or elvitegravir (EGV) carrying different HIV-1 variants.


RESULTS
A total of 83 patients infected by B HIV-1 subtype (64%) or non-B HIV-1 variants (36%) were evaluated. No primary mutations to RAL or EGV were found in the inte-grase sequences analyzed. Secondary mutations were detected in only 5 patients. Additional mutations were found in both in B and non-B variants. According to the geno2pheno algorithm, some of the secondary mutations detected (L74V, E138K, G163RS, and V151I) have been associated with a reduced estimated susceptibility to RAL and only the E138K mutation has been associated with a decreased estimated susceptibility to EGV. No virological failure was observed after RAL was administrated in 17 patients carrying 1 or more additional substitutions in the absence of primary or secondary mutations.


CONCLUSIONS
No primary resistance mutations to INSTI were found in treatment-naïve or -experienced patients infected with B or non-B HIV-1 variants. The vast majority had some polymorphic and non-polymorphic substitutions; however response to RAL was excellent in patients who harbored one or more of these mutations. We could not identify any clinical factors associated with the presence of any of these mutations.
Infectious Diseases Department, Hospital Universitario Ramón y Cajal and IRYCIS, Madrid, Spain. cgutierrezm.hrc@salud.madrid.org
Carolina
C
Gutiérrez
Beatriz
B
Hernández-Novoa
María Jesús
MJ
Pérez-Elías
Ana María
AM
Moreno
Africa
A
Holguín
Fernando
F
Dronda
José Luis
JL
Casado
Santiago
S
Moreno
D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype; D015995:Prevalence; D011760:Pyrrolidinones / Q000494:pharmacology / Q000627:therapeutic use; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D013030:Spain; D019562:Viral Load
D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D015363:Quinolones; D000068898:Raltegravir Potassium; C509700:elvitegravir; D019427:HIV Integrase