Demographic and clinical characteristics of the study population compared to National Governmental Report of Panamanian HIV cases (1984–2012).

<p>Data are No. (%). Abbreviations: HIV, human immunodeficiency virus; n.s. not significant differences; p<0.05, means significant differences.</p><p>p value of the two-sample proportion Z-test result.</p><p>^a As indicated by the total of accumulative AIDS and HIV carriers first time diagnosed between September 1984 to September 2012.</p><p>^b As indicated by the total of accumulative AIDS and HIV carriers first time diagnosed between 1984 to 2010.</p

Phylogenetic Neighbor-Joining tree of HIV <i>pol</i> gene sequences from Panamanian infected subjects sampled from 2007 to 2013.

<p>(A) Panamanian HIV (black circles) are clustered with highly support within the clade of subtype B (n = 648), subtype F1 (n = 1) and subtype C (n = 1) reference sequences. For clarification purposes, branches have been compressed by each subtype. Bootstrap values higher than 80 are shown at branches. (B) Clustering of subtype B sequences defined by colored range of diagnostic age.</p

Molecular Epidemiology of HIV-1 in Panama: Origin of Non-B Subtypes in Samples Collected from 2007 to 2013

<div><p>Phylogenetic studies have suggested that the HIV-1 epidemic in the Americas is mainly dominated by HIV subtype B. However, countries of South America and the Caribbean have recently reported changes in their circulating HIV-1 genetic profiles. The aim of this study was to characterize the molecular profile of the HIV-1 epidemic in Panama by the analysis of 655 polymerase gene (<i>pol</i>) sequences that were obtained from HIV-infected Panamanians diagnosed between 1987 and 2013. Blood samples were collected from recently infected, antiretroviral drug-naïve and treatment-experienced subjects since mid-2007 to 2013. Viral RNA from plasma was extracted and sequences of HIV protease and reverse transcriptase genes were obtained. Bootscanning and phylogenetic methods were used for HIV subtyping and to trace the putative origin of non-B subtype strains. Our results showed that HIV-1 infections in Panama are dominated by subtype B (98.9%). The remaining 1.1% is represented by a diverse collection of recombinant variants including: three URFs_BC, one CRF20_BG, and one CRF28/29_BF, in addition to one subtype F1 and one subtype C, none of which were previously reported in Panama. The non-B subtype variants detected in Panama were probably introduced from Brazil (subtype F1 and CRF28/29_BF), Cuba (CRF20_BG), Dominican Republic (URFs_BC) and India (subtype C). Panama is the geographical vertex that connects the North with South America and the Caribbean through trade and cultural relations, which may explain the observed introductions of non-B subtype HIV-1 variants from both the Caribbean and South America into this Central American country.</p></div

Geographic distribution of Panamanian subjects living with HIV participating in the study.

<p>Map of Panama indicating the number of infected subjects located in each of the nine provinces (Bocas del Toro, Chiriquí, Veraguas, Herrera, Los Santos, Coclé, Colón, Panamá and Darién) and native territories of Comarcas Ngöbe Buglé, Kuna Yala and Emberá Wouman. The pie chart that represents the proportion of subjects located at the different districts from eastern Panama which includes the provinces of Panama, Colón, Darién and Comarca Kuna Yala.</p

<i>pol</i> gene ML phylogenetic tree of non-B HIV-1 Panamanian sequences and 50 highly similar (nucleotide similarity > 94%) sequences from other countries selected with Blastn analyses.

<p>(A) BC recombinant. (B) BF1 recombinant. (C) BG recombinant. (D) subtype F1 (E) subtype C. Panamanian non-B sequences are shown in highlighted red color. The tree was rooted using reference subtype sequences. The numbers along branches correspond to aLRT values. Bar is in nucleotide substitutions per site. The pie chart shows the proportion of countries represented by the Blastn analysis. Countries correspond with defined colors which are specified in each pie chart.</p

Epidemiological information of Panamanian subjects with non-B subtypes and recombinant variants BG, BC and BF.

<p>Abbreviations: M, male; F, female; U, not known; HE, heterosexual; ASY, asymptomatic; AIDS, acquired inmunedeficiency syndrome; NA, naïve; EX, experienced; NRTI, nucleosidic reverse transcriptase inhibitor; NNRTI, non-nucleosidic reverse transcriptase inhibitor.</p

ML phylogenetic tree of HIV-1 subtype B <i>pol</i> (∼1000 pb) sequences circulating in Panama (<i>n</i> = 761) and other Central American countries (<i>n</i> = 694).

<p>The branches are colored according to the geographic origin of each sequence, as indicated at the legend (top left). Red shaded boxes highlight the position of the twelve Panamanian HIV-1 subtype B clades (B_PA-I to B_PA-XII). Gray shaded box highlights the position of the major Central American clade (B_CAM). The <i>a</i>LRT support values for each clade are indicated at bottom. The tree was rooted using HIV-1 subtype D reference sequences. The branch lengths are drawn to scale with the bar at the bottom indicating nucleotide substitutions per site.</p

Demographic history of HIV-1 Panamanian clades of large size (B_PA-I to B_PA-IV).

<p>Effective number of infections (<i>y</i>-axis; log₁₀ scale) through time (x-axis; calendar years) estimated using Bayesian skyline (A, C, E and G) and logistic (B, D and F) or exponential (H) growth coalescent models are shown for each of the four HIV-1 Panamanian clades. Median estimates of the effective number of infections (solid line) and 95% HPD intervals of the estimates (dashed lines) are shown in each graphic. The median growth rate (with the corresponding 95% credibility interval in parenthesis) of each clade estimated under logistic or exponential growth model is indicated in the upper left corner.</p

Epidemiological information of Panamanian subjects infected with major HIV-1 clades.

<p>Data are: number (%).</p>a<p>Unknown/NA: subjects decide not to answer about their mode of infection or information was not available.</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