PDR temporal trends.

<p>PDR was estimated by year of enrolment using the HIVdb tool from Sanger sequences. Individuals with drug resistance were defined as those with at least low-level resistance (Stanford penalty score ≥15) to any drug of the corresponding class. A. PDR temporal trends by drug class. B. PDR temporal trends for the most widely used antiretroviral regimens in Nicaragua. C-E PDR temporal trends by drug, divided by drug class; only drugs currently used in clinical practice in the Nicaraguan context are shown. *p<0.05; linear regression, slope different to 0; the color corresponds to the significant category.</p

HIV PDR and demographic variables in heterosexuals and MSM.

<p>HIV PDR and demographic variables in heterosexuals and MSM.</p

Demographic and clinical characteristics of the participants.

<p>Demographic and clinical characteristics of the participants.</p

PDR temporal trends.

<p>PDR was estimated by year of enrolment using the HIVdb tool from Sanger sequences. Individuals with drug resistance were defined as those with at least low-level resistance (Stanford penalty score ≥15) to any drug of the corresponding class. A. PDR temporal trends by drug class. B. PDR temporal trends for the most widely used antiretroviral regimens in Nicaragua. C-E PDR temporal trends by drug, divided by drug class; only drugs currently used in clinical practice in the Nicaraguan context are shown. *p<0.05; linear regression, slope different to 0; the color corresponds to the significant category.</p

HIV pre-treatment drug resistance in Nicaragua.

<p>HIV pre-treatment drug resistance in Nicaragua.</p

NNRTI PDR trends in Nicaragua.

<p>PDR was estimated by year of enrolment using the HIVdb tool from Sanger sequences. Individuals with drug resistance were defined as those with at least low-level resistance (Stanford penalty score ≥15) to any NNRTI. A. NNRTI PDR temporal trends; lines represent 95% confidence intervals. B. NNRTI PDR mutation frequency trends; only surveillance drug resistance mutations to NNRTI with frequency over 0.5% and E138A are included. C. PDR levels per year for efavirenz; drug resistance levels per year are classified according to the Stanford Score, as explained for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164156#pone.0164156.g003" target="_blank">Fig 3</a>. Significant trends are shown; linear regression, slope different to 0; the color corresponds to the significant category. The number of patients enrolled by year was 17, 88, 69, 61, and 48 for 2011, 2012, 2013, 2014, and 2015 respectively.</p

Surveillance drug resistance mutation frequency at different detection sensitivity thresholds.

<p>Drug resistance mutation frequency was determined at different thresholds using next generation sequencing as explained in Methods. Cumulative frequency for each mutation is shown. Only surveillance drug resistance mutations are shown, and are classified by drug class.</p

HIV pre-treatment drug resistance by year of enrolment.

<p>HIV pre-treatment drug resistance by year of enrolment.</p

Phylogenetic relations between HIV sequences with PDR.

<p>A Maximum Likelihood tree, built with the General Time Reversible + I + Γ model, without including drug resistance positions is shown. 1000 bootstrap repetitions were used to assess confidence. Viruses with PDR to PI (purple), NRTI (green), NNRTI (red) and more than one ARV class (blue) are colored. Reference sequences were obtained from Los Alamos HIV Database (bold). Five clusters of viral sequences with PDR with bootstrap values over 90% are amplified. Circle, females; empty triangle, heterosexual males; full triangle, self-identified men who have sex with men; square, unknown risk factor.</p

PDR levels per antiretroviral drug.

<p>PDR levels per drug were estimated using the Stanford HIVdb tool, from Sanger sequences, and classified according to the Stanford Score (SS) as high: SS≥60, intermediate: SS 30–59, or low: 15–29.</p