Decreasing prevalence of transmitted drug resistance among ART-naive HIV-1-infected patients in Iceland, 1996–2012

ABSTRACT

Introduction: Resistance to antiretroviral drugs can complicate the management of HIV-1 infection and impair control of its spread. The aim of the current study was to investigate the prevalence and transmission of HIV-1 drug resistance among 106 antiretroviral therapy (ART)-naïve patients diagnosed in Iceland (1996–2012).

Methods: HIV-1 polymerase sequences were analysed using the Calibrated Population Resistance tool. Domestic spread of transmitted drug resistance (TDR) was investigated through maximum likelihood and Bayesian approaches.

Results: Among ART-naïve patients, the prevalence of TDR to any of the following classes (NRTIs, NNRTIs and PIs) was 8.5% (95% CI: 4.5%- 15.4%): 6.6% to NRTIs, 0.9% to NNRTIs, and 1.9% to PIs. The most frequent NRTI mutation detected was T215C/D (n=7, 5.7%). The only NNRTI mutation detected was K103N (n=1, 0.9%). PI mutations detected were M46I (n=1, 0.9%) and L90M (n=1, 0.9%). Six patients harbouring T215C/D, were linked in a supported phylogenetic cluster. No significant association was found between TDR and demographic or risk groups. Trend analysis showed a decrease in the prevalence of TDR (1996–2012, p=0.003).

Conclusions: TDR prevalence in Iceland was at a moderate level and decreased during 1996-2012. Screening for TDR is recommended to limit its local spread and to optimize HIV-1 therapy.

A bbreviations: ART: Anti-retroviral therapy; ARV: antiretroviral; ATV/r: atazanavir/ritonavir; AZT: azidothymidine; BEAST: Bayesian evolutionary analysis by sampling trees; CI: confidence interval; CPR: calibrated population resistance; CRF: circulating recombinant form; d4T: stavudine; EFV: efavirenz; FET: Fishers’ exact test; FPV/r: fosamprenavir/ritonavir; HET: heterosexual; IDU: injection drug use; IDV/r: indinavir/ritonavir; LPV/r: lopinavir/ritonavir; MSM: men who have sex with men; M-W: Mann–Whitney U test; NFV: nelfinavir; NNRTIs: non-nucleoside reverse transcriptase inhibitors; NRTIs: nucleoside reverse transcriptase inhibitors; NVP: nevirapine; PIs: protease inhibitors; pol: polymerase gene; SDRM: surveillance drug resistance mutation; SQV/r: saquinavir/ritonavir; TDR: transmitted drug resistance

KEYWORDS:

• Phylogeny
• resistance
• trend
• transmission
• BEAST

Acknowledgements

We would like to thank Guðrún Baldvinsdóttir and Thora Björg Björnsdóttir at the Department of Virology, Landspitali University Hospital for sample collection. We also thank Eva Friman at MEMEG, Institution of Biology, Lund University for performing DNA sequencing.

Disclosure statement

No potential conflict of interest was reported by the authors.

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Additional information

Funding

The study was supported by funding from the Swedish Research Council, Sweden [350-2012-6628 for JE and 321-2012-3274 for PM]. MS was supported by a scholarship from the University of Jordan [ref. 1/2/5/A/259-2013]. The authors were also supported by the Faculty of Medicine, Lund University, Sweden, and by the University of Iceland Research Fund under no specific grants numbers.