Differences in the integrase and reverse transcriptase transmitted resistance patterns in Northern Poland

Abstract

Introduction: With the widespread introduction of the integrase (In) inhibitors into clinical practice, transmission of drug resistance to this class of antiretroviral medications may expand. The aim of this study was to analyze the recent patterns of In resistance in treatment naive individuals in Northern Poland and its association with transmitted protease (PR) and reverse transcriptase (RT) mutations.

Methods: Study included 172 PR, RT and InI sequences from antiretroviral treatment naive HIV-1 infected patients linked to care in Northern Poland from 2010 to 2015. Drug resistance was interpreted based on the WHO surveillance and IAS-USA mutation lists. For phylogeny maximum likelihood and Bayesian Monte Carlo Markov Chain analyses were used.

Results: Overall rate of transmitted drug resistance was 12.21%. Nucleoside reverse transcriptase inhibitor (NRTI) resistance associated substitutions were found in 11.05% of cases and non-nucleoside reverse transcriptase inhibitor resistance variants in 1.16%. In multivariate models transmitted resistance strongly associated with subtype D infections [66.67% compared to the 3.84% for subtype B (p=0.001)]. No transmission of major protease or integrase mutations were observed. Polymorphisms associated with resistance against integrase inhibitor, mostly E157Q, were found in 21.5% sequences and associated with female (31.91% vs. 15.2% for male, p=0.01), injection drug use (84.21% compared to 22.08% for heterosexual and 1.39% for men-who-have-sex-with-men transmissions, p<0.0001) as well as hepatitis C coinfection [63.64% for positive, versus 8.57% for HCV antibody negative, p<0.0001]. Clusters of nucleoside reverse transcriptase mutations in subtype D and integrase E157Q variants in subtype B were observed.

Conclusions: Transmitted drug resistance frequency was high in subtype D but limited to clustered NRTI mutations, being infrequent among subtype B infected cases. Despite lack of major integrase resistance in treatment naive patients, variants potentially affecting susceptibility to this class were common, which indicates the potential need for extended surveillance in the near future.

Keywords: Integrase mutations; Non-B subtypes; Transmission clusters; Transmitted drug resistance.