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Multicenter Study
. 2014 Mar 17;9(3):e90710.
doi: 10.1371/journal.pone.0090710. eCollection 2014.

Clinically relevant transmitted drug resistance to first line antiretroviral drugs and implications for recommendations

Susana Monge  1 , Vicente Guillot  2 , Marta Alvarez  2 , Natalia Chueca  2 , Natalia Stella  3 , Alejandro Peña  2 , Rafael Delgado  4 , Juan Córdoba  5 , Antonio Aguilera  6 , Carmen Vidal  7 , Federico García  2 ; CoRIS
Collaborators, Affiliations
Multicenter Study

Clinically relevant transmitted drug resistance to first line antiretroviral drugs and implications for recommendations

Susana Monge et al. PLoS One. .

Abstract

Background: The aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted Drug Resistance (TDR) defined by the 2009 update of the WHO SDRM list.

Methods: We analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain) between 2007-2011. Using the Stanford algorithm "Low-level resistance", "Intermediate resistance" and "High-level resistance" categories were considered as "Resistant".

Results: 70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs [6.8% (95%Confidence Interval: 5.8-7.7)], and 221 harbored TDR using the WHO list [7.9% (6.9-9.0)]. Differences were due to a lower prevalence in clinically relevant resistance for NRTIs [2.3% (1.8-2.9) vs. 3.6% (2.9-4.3) by the WHO list] and PIs [0.8% (0.4-1.1) vs. 1.7% (1.2-2.2)], while it was higher for NNRTIs [4.6% (3.8-5.3) vs. 3.7% (3.0-4.7)]. While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02).

Conclusions: Prevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Prevalence of TDR (WHO SDRM estimates) by antiretroviral class between 2007 and 2011.
NRTI: nucleoside reverse transcriptase inhibitors; NNRTI: non-nucleoside reverse transcriptase inhibitors; PI: protease inhibitors. * p value for Chi-square test for trend.
Figure 2
Figure 2. Prevalence of clinically relevant resistance to first line drugs (Stanford HIVdb) by antiretroviral class between 2007 and 2011.
NRTI: nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine and tenofovir); NNRTI: non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine); PI: protease inhibitors (atazanavir, darunavir and lopinavir). * p value for Chi-square test for trend.
See this image and copyright information in PMC

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