HIV integrase variability and genetic barrier in antiretroviral naïve and experienced patients

Antonio Piralla,Stefania Paolucci,Roberto Gulminetti,Giuditta Comolli,Fausto Baldanti

doi:10.1186/1743-422x-8-149

Antonio Piralla, Stefania Paolucci + Show 3 more

Open Access

https://doi.org/10.1186/1743-422x-8-149

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Abstract

BackgroundHIV-1 integrase (IN) variability in treatment naïve patients with different HIV-1 subtypes is a major issue. In fact, the effect of previous exposure to antiretrovirals other than IN inhibitors (INI) on IN variability has not been satisfactorily defined. In addition, the genetic barrier for specific INI resistance mutations remains to be calculated.MethodsIN variability was analyzed and compared with reverse transcriptase (RT) and protease (PR) variability in 41 treatment naïve and 54 RT inhibitor (RTI) and protease inhibitor (PRI) experienced patients from subjects infected with subtype B and non-B strains. In addition, four HIV-2 strains were analyzed in parallel. Frequency and distribution of IN mutations were compared between HAART-naïve and RTI/PI-experienced patients; the genetic barrier for 27 amino acid positions related to INI susceptibility was calculated as well.ResultsPrimary mutations associated with resistance to INI were not detected in patients not previously treated with this class of drug. However, some secondary mutations which have been shown to contribute to INI resistance were found. Only limited differences in codon usage distribution between patient groups were found. HIV-2 strains from INI naïve patients showed the presence of both primary and secondary resistance mutations.ConclusionExposure to antivirals other than INI does not seem to significantly influence the emergence of mutations implicated in INI resistance. HIV-2 strain might have reduced susceptibility to INI.

Highlights

HIV-1 integrase (IN) variability in treatment naïve patients with different HIV-1 subtypes is a major issue
It has been observed that failure of highly active antiretroviral therapy (HAART) including RAL might be related to the emergence of drug-resistant virus variants [10,11,12,13,14,15], and amino acid changes associated with resistance to integrase inhibitors (INI) have been reported [16,17,18]
Study population Nucleotide and amino acid integrase variability was analyzed in 41 HAART-naïve patients, and 54 RT inhibitor (RTI)/ PI-experienced patients

Summary

Introduction

HIV-1 integrase (IN) variability in treatment naïve patients with different HIV-1 subtypes is a major issue. Nor do we fully understand the potential impact of naturally occurring ancillary mutations with respect to: i) promotion of RAL resistance associated mutations, ii) improvement of the activity of mutated IN and iii) HIV-1 replicative capacity. It is unclear whether drug pressure on the Pol gene by RT and PR inhibitors might influence the emergence of primary or ancillary RAL mutations. It is important to define the variability of the IN gene in treatment-naïve and HAART-experienced patients in different HIV-1 subtypes

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