Integrase strand-transfer inhibitor polymorphic and accessory resistance substitutions in patients with acute/recent HIV infection.
The most recent guidelines suggest using integrase strand-transfer inhibitors (InSTIs) as the preferred antiretroviral regimens for naive HIV-infected individuals. However, resistance to InSTIs is not monitored in many centres at baseline. This study aimed to evaluate the prevalence of InSTI resistance substitutions in newly diagnosed patients with acute/recent HIV infection.



Genotypic drug resistance tests were performed in all consecutive patients prospectively enrolled with a documented infection of <6 months, from 12 May 2015 to 12 May 2016. Sequences were obtained by high-throughput sequencing.



Five out of 36 consecutive patients (13.89%, 95% CI = 4.67-29.5) with acute/recent HIV infection were detected to have strains carrying InSTI polymorphisms or substitutions conferring low-level resistance to raltegravir and elvitegravir. Four patients had the 157Q polymorphism and one patient had the Q95K substitution. All cases were MSM patients infected with subtype B strains. Viral loads ranged from 2.92 to 6.95 log10copies/mL. In all cases, the mutational viral load was high. Three patients initiated dolutegravir-based regimens and became undetectable at first viral load control. There were no major viral or epidemiological differences when compared with patients without InSTI substitutions.



Although signature InSTI substitutions (such as Y143R/C, N155H or Q148K/R/H) were not detected, polymorphisms and substitutions conferring low-level resistance to raltegravir and elvitegravir were frequently found in a baseline genotypic test. All cases were infected with subtype B, the most frequent in Europe. In the context of primary HIV infection, virological response should be carefully monitored to evaluate the impact of these InSTI polymorphisms and substitutions.
Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain jambrosioni@intramed.net.
J
J
Ambrosioni
Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
D
D
Nicolás
Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
C
C
Manzardo
Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
F
F
Agüero
Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
J L
JL
Blanco
Laboratory of Virology, Microbiology Service, Hospital Clinic-ISGLOBAL, University of Barcelona, Barcelona, Spain.
M M
MM
Mosquera
Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
J
J
Peñafiel
Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
J M
JM
Gatell
Laboratory of Virology, Microbiology Service, Hospital Clinic-ISGLOBAL, University of Barcelona, Barcelona, Spain.
M A
MA
Marcos
Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
J M
JM
Miró
D000328:Adult; D019943:Amino Acid Substitution; D024882:Drug Resistance, Viral; D005060:Europe; D005260:Female; D060005:Genotyping Techniques; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D059645:Mutation Rate; D020125:Mutation, Missense; D011446:Prospective Studies; D017422:Sequence Analysis, DNA
D019428:HIV Integrase Inhibitors; D019427:HIV Integrase