scholarly journals Cuban history of CRF19 recombinant subtype of HIV-1

2021 ◽  
Vol 17 (8) ◽  
pp. e1009786
Author(s):  
Anna Zhukova ◽  
Jakub Voznica ◽  
Miraine Dávila Felipe ◽  
Thu-Hien To ◽  
Lissette Pérez ◽  
...  
Keyword(s):  
Large Data ◽  
Temporal Analysis ◽  
Rapid Progression ◽  
Resistance Mutations ◽  
Data Set ◽  
Early Introduction ◽  
Spatio Temporal ◽  
Sex With Men ◽  
Founder Event ◽  
Hiv 1

CRF19 is a recombinant form of HIV-1 subtypes D, A1 and G, which was first sampled in Cuba in 1999, but was already present there in 1980s. CRF19 was reported almost uniquely in Cuba, where it accounts for ∼25% of new HIV-positive patients and causes rapid progression to AIDS (∼3 years). We analyzed a large data set comprising ∼350 pol and env sequences sampled in Cuba over the last 15 years and ∼350 from Los Alamos database. This data set contained both CRF19 (∼315), and A1, D and G sequences. We performed and combined analyses for the three A1, G and D regions, using fast maximum likelihood approaches, including: (1) phylogeny reconstruction, (2) spatio-temporal analysis of the virus spread, and ancestral character reconstruction for (3) transmission mode and (4) drug resistance mutations (DRMs). We verified these results with a Bayesian approach. This allowed us to acquire new insights on the CRF19 origin and transmission patterns. We showed that CRF19 recombined between 1966 and 1977, most likely in Cuban community stationed in Congo region. We further investigated CRF19 spread on the Cuban province level, and discovered that the epidemic started in 1970s, most probably in Villa Clara, that it was at first carried by heterosexual transmissions, and then quickly spread in the 1980s within the “men having sex with men” (MSM) community, with multiple transmissions back to heterosexuals. The analysis of the transmission patterns of common DRMs found very few resistance transmission clusters. Our results show a very early introduction of CRF19 in Cuba, which could explain its local epidemiological success. Ignited by a major founder event, the epidemic then followed a similar pattern as other subtypes and CRFs in Cuba. The reason for the short time to AIDS remains to be understood and requires specific surveillance, in Cuba and elsewhere.

scholarly journals Cuban history of CRF19 recombinant subtype of HIV-1

2021 ◽  
Author(s):  
Anna Zhukova ◽  
Jakub Voznica ◽  
Miraine Dávila Felipe ◽  
Thu-Hien To ◽  
Lissette Pérez ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Temporal Analysis ◽  
Recombinant Form ◽  
Rapid Progression ◽  
Resistance Mutations ◽  
Data Set ◽  
Early Introduction ◽  
The World ◽  
Sex With Men ◽  
Hiv 1

AbstractCRF19 is a recombinant form of HIV-1 subtypes D, A1 and G, which was first sampled in Cuba in 1999, but was already present there in 1980s. CRF19 was reported almost uniquely in Cuba, where it accounts for ~25% of new HIV-positive patients and causes rapid progression to AIDS (~ 3 years).We analyzed a large data set comprising ~ 350 pol and env sequences sampled in Cuba over the last 15 years and ~ 350 from Los Alamos database. This data set contained both CRF19 (~ 315), and A1, D and G sequences. We performed and combined analyses for the three A1, G and D regions, using fast maximum likelihood approaches, including: (1) phylogeny reconstruction, (2) spatio-temporal analysis of the virus spread, and ancestral character reconstruction for (3) transmission mode and (4) drug resistance mutations (DRMs). This allowed us to acquire new insights on the CRF19 origin and transmission patterns. We showed that CRF19 recombined between 1966 and 1977, most likely in Cuban community stationed in Congo region. We further investigated CRF19 spread on the Cuban province level, and discovered that the epidemic started in 1970s, most probably in Villa Clara, that it was at first carried by heterosexual transmissions, and then quickly spread in the 1980s within the “men having sex with men” (MSM) community, with multiple transmissions back to heterosexuals. The analysis of the transmission patterns of common DRMs showed mostly acquired drug resistance rather than transmitted one.Our results show a very early introduction of CRF19 in Cuba, which could explain its local epidemiological success. Ignited by a major founder event, the epidemic then followed a similar pattern as other subtypes and CRFs in Cuba. The reason for the short time to AIDS remains to be understood and requires specific surveillance, in Cuba and elsewhere.Author summaryCRF19 is a recombinant form of HIV-1, which causes rapid progression to AIDS (~ 3 years versus 5 – 10 years for other subtypes and CRFs). CRF19 is reported almost uniquely in Cuba, where it is highly prevalent (~ 25%) among newly detected HIV-1 patients. In this study, we found that CRF19 most likely recombined around the 1970s in the Cuban community that was stationed in Democratic Republic of the Congo and Angola at that time. It was introduced very early into the Cuban province of Villa Clara, from where it had several introductions to La Habana in the 1980s and then further spread to other Cuban provinces. The CRF19 epidemic most probably started with heterosexual transmissions, followed in the 1980s by multiple introductions into “men having sex with men” (MSM) community, followed by multiple transmissions back to heterosexuals (often females). The early introduction of CRF19 into Cuba most likely explains its success, not observed in other parts of the world. However, importantly, its rapid progression to AIDS makes it crucial to survey CRF19 sub-epidemics not only in Cuba, but also in other parts of the world having regular exchanges with Cuba.

scholarly journals Standardized Comparison of the Relative Impacts of HIV-1 Reverse Transcriptase (RT) Mutations on Nucleoside RT Inhibitor Susceptibility

2012 ◽  
Vol 56 (5) ◽  
pp. 2305-2313 ◽  
Author(s):  
George L. Melikian ◽  
Soo-Yon Rhee ◽  
Jonathan Taylor ◽  
W. Jeffrey Fessel ◽  
David Kaufman ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
San Francisco ◽  
Resistance Mutation ◽  
Dynamic Susceptibility ◽  
Least Squares Regression ◽  
Resistance Mutations ◽  
Data Set ◽  
New Findings ◽  
The Impact ◽  
Hiv 1

ABSTRACTDetermining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs have highly variable dynamic susceptibility ranges, making it difficult to determine the relative effect of an RT mutation on susceptibility to different NRTIs. In this study, we analyzed 1,273 genotyped HIV-1 isolates for which phenotypic results were obtained using the PhenoSense assay (Monogram, South San Francisco, CA). We used a parsimonious feature selection algorithm, LASSO, to assess the possible contributions of 177 mutations that occurred in 10 or more isolates in our data set. We then used least-squares regression to quantify the impact of each LASSO-selected mutation on each NRTI. Our study provides a comprehensive view of the most common NRTI resistance mutations. Because our results were standardized, the study provides the first analysis that quantifies the relative phenotypic effects of NRTI resistance mutations on each of the NRTIs. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation.

scholarly journals Comparing mutational pathways to lopinavir resistance in HIV-1 subtypes B versus C

2020 ◽  
Author(s):  
Susana Posada-Céspedes ◽  
Gert Van Zyl ◽  
Hesam Montazeri ◽  
Jack Kuipers ◽  
Soo-Yon Rhee ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Genotype Data ◽  
Resistance Mutations ◽  
Subtype C ◽  
Cross Sectional ◽  
Data Set ◽  
Hiv Drug Resistance ◽  
Subtype B ◽  
Hiv 1 ◽  
Temporal Ordering

AbstractAlthough combination antiretoviral therapies seem to be effective at controlling HIV-1 infections regardless of the viral subtype, there is increasing evidence for subtype-specific drug resistance mutations. The order and rates at which resistance mutations accumulate in different subtypes also remain poorly understood. Here, we present a methodology for the comparison of mutational pathways in different HIV-1 subtypes, based on Hidden Conjunctive Bayesian Networks (H-CBN), a probabilistic model for inferring mutational pathways from cross-sectional genotype data. We introduce a Monte Carlo sampling scheme for learning H-CBN models on a large number of resistance mutations and develop a statistical test to assess differences in the inferred mutational pathways between two groups. We apply this method to the temporal progression of mutations conferring resistance to the protease inhibitor lopinavir in a large cross-sectional data set of South African individuals living with HIV-1 subtype C, as well as a genotype data set of subtype B infections derived from the Stanford HIV Drug Resistance Database and the Swiss HIV Cohort Study. We find strong support for different initial mutational events in the protease, namely at residue 46 in subtype B and at residue 82 in subtype C. Our results also show that mutations can accumulate along various alternative paths within subtypes, as opposed to a unique total temporal ordering. Furthermore, the maximum likelihood mutational networks for subtypes B and C share only 7 edges (Jaccard distance 0.802) and imply many different evolutionary pathways. Beyond HIV drug resistance, the statistical methodology is applicable more generally for the comparison of inferred mutational pathways between any two groups.Author summaryThere is a disparity in the distribution of infections by HIV-1 subtype in the world. Subtype B is predominant in America, Western Europe and Australia, and most therapeutic strategies are based on research and clinical studies on this subtype. However, non-B subtypes represent the majority of global HIV-1 infections; e.g., subtype C alone accounts for nearly half of all HIV-1 infections. We present a statistical framework enabling the comparison of patterns of accumulating mutations in different HIV-1 subtypes. Specifically, we study lopinavir resistance pathways in HIV-1 subtypes B versus C, but the methodology can be generally applied to compare the temporal ordering of genetic events in different subgroups.

GIS-based Spatio-Temporal and Geostatistical Analysis of Groundwater Parameters of Lahore Region Pakistan and their Source Characterization

2021 ◽  
Author(s):  
Sadia Ismail ◽  
M Farooq Ahmed
Keyword(s):  
Water Quality ◽  
Groundwater Quality ◽  
Water Quality Index ◽  
Physicochemical Parameters ◽  
Quality Index ◽  
Large Data ◽  
Quality Parameters ◽  
Source Characterization ◽  
Data Set ◽  
Spatio Temporal

Abstract Assessment of groundwater quality is critical, especially in the areas where it is continuously deteriorating due to unplanned industrial growth. This study utilizes GIS-based spatio-temporal and geostatistics tools to characterize the groundwater quality parameters of Lahore region. For this purpose, a large data set of the groundwater quality parameters (for a period of 2005–2016) was obtained from the deep unconfined aquifers. GIS-based water quality index (WQI) and entropy water quality index (EWQI) models were prepared using 15 water quality parameters pH (power of hydrogen), TDS (Total dissolve solids), EC (Electrical conductivity), TH (Total hardness), Ca2+ (Calcium), Mg2+ (Magnesium), Na+ (Sodium), K+ (Potassium), Cl− (Chloride), As (Arsenic), F (Fluoride), Fe (Iron), HCO3− (Bicarbonate), NO3− (Nitrate), and SO42− (Sulfate). The data analysis exhibits that 12% of the groundwater samples fell within the category of poor quality that helped to identify the permanent epicenters of deteriorating water quality index in the study area. As per the entropy theory, Fe, NO3−, K, F, SO42− and As, are the major physicochemical parameters those influence groundwater quality. The spatio-temporal analysis of the large data set revealed an extreme behavior in pH values along the Hudiara drain, and overall high arsenic concentration levels in most of the study area. The geochemical analysis shows that the groundwater chemistry is strongly influence by subsurface soil water interaction. The research highlights the significance of using GIS-based spatio-temporal and geostatistical tools to analyze the large data sets of physicochemical parameters at regional level for the detailed source characterization studies.

scholarly journals Epidemiological and Molecular Characteristics of HIV-1 Infection in a Sample of Men Who Have Sex With Men in Brazil: Phylogeography of Major Subtype B and F1 Transmission Clusters

2020 ◽  
Vol 11 ◽  
Author(s):  
Ágabo Macêdo da Costa e Silva ◽  
Mônica Nogueira da Guarda Reis ◽  
Thaís Augusto Marinho ◽  
Nara Rúbia de Freitas ◽  
Sheila Araújo Teles ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
The State ◽  
Enzyme Linked Immunosorbent Assay ◽  
Molecular Characteristics ◽  
Resistance Mutations ◽  
Subtype B ◽  
Sex With Men ◽  
Hiv 1

This study describes human immunodeficiency virus 1 (HIV-1) prevalence, associated factors, viral genetic diversity, transmitted drug resistance (TDR), and acquired drug resistance mutations (DRM) among a population of 522 men who have sex with men (MSM) recruited by the respondent-driven sampling (RDS) method, in Goiânia city, the capital of the State of Goiás, Central-Western Brazil. All serum samples were tested using a four-generation enzyme-linked immunosorbent assay (ELISA), and reactive samples were confirmed by immunoblotting. Plasma RNA or proviral DNA was extracted, and partial polymerase (pol) gene including the protease/reverse transcriptase (PR/RT) region was amplified and sequenced. HIV-1 subtypes were identified by phylogenetic inference and by bootscan analysis. The time and location of the ancestral strains that originated the transmission clusters were estimated by a Bayesian phylogeographic approach. TDR and DRM were identified using the Stanford databases. Overall, HIV-1 prevalence was 17.6% (95% CI: 12.6–23.5). Self-declared black skin color, receptive anal intercourse, sex with drug user partner, and history of sexually transmitted infections were factors associated with HIV-1 infection. Of 105 HIV-1-positive samples, 78 (74.3%) were sequenced and subtyped as B (65.4%), F1 (20.5%), C (3.8%), and BF1 (10.3%). Most HIV-1 subtype B sequences (67%; 34 out of 51) branched within 12 monophyletic clusters of variable sizes, which probably arose in the State of Goiás between the 1980s and 2010s. Most subtype F1 sequences (n = 14, 88%) branched in a single monophyletic cluster that probably arose in Goiás around the late 1990s. Among 78 samples sequenced, three were from patients under antiretroviral therapy (ART); two presented DRM. Among 75 ART-naïve patients, TDR was identified in 13 (17.3%; CI 95%: 9.6–27.8). Resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTI) predominated (14.7%), followed by nucleoside reverse transcriptase inhibitor (NRTI) mutations (5.3%) and protease inhibitor (PI) mutations (1.3%). This study shows a high prevalence of HIV-1 associated with sexual risk behaviors, high rate of TDR, and high genetic diversity driven by the local expansion of different subtype B and F1 strains. These findings can contribute to the understanding about the dissemination and epidemiological and molecular characteristics of HIV-1 among the population of MSM living away from the epicenter of epidemics in Brazil.

scholarly journals Comparing mutational pathways to lopinavir resistance in HIV-1 subtypes B versus C

2021 ◽  
Vol 17 (9) ◽  
pp. e1008363
Author(s):  
Susana Posada-Céspedes ◽  
Gert Van Zyl ◽  
Hesam Montazeri ◽  
Jack Kuipers ◽  
Soo-Yon Rhee ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Strong Support ◽  
Monte Carlo Sampling ◽  
Resistance Mutations ◽  
Subtype C ◽  
Cross Sectional ◽  
Data Set ◽  
Hiv Drug Resistance ◽  
Subtype B ◽  
Hiv 1

Although combination antiretroviral therapies seem to be effective at controlling HIV-1 infections regardless of the viral subtype, there is increasing evidence for subtype-specific drug resistance mutations. The order and rates at which resistance mutations accumulate in different subtypes also remain poorly understood. Most of this knowledge is derived from studies of subtype B genotypes, despite not being the most abundant subtype worldwide. Here, we present a methodology for the comparison of mutational networks in different HIV-1 subtypes, based on Hidden Conjunctive Bayesian Networks (H-CBN), a probabilistic model for inferring mutational networks from cross-sectional genotype data. We introduce a Monte Carlo sampling scheme for learning H-CBN models for a larger number of resistance mutations and develop a statistical test to assess differences in the inferred mutational networks between two groups. We apply this method to infer the temporal progression of mutations conferring resistance to the protease inhibitor lopinavir in a large cross-sectional cohort of HIV-1 subtype C genotypes from South Africa, as well as to a data set of subtype B genotypes obtained from the Stanford HIV Drug Resistance Database and the Swiss HIV Cohort Study. We find strong support for different initial mutational events in the protease, namely at residue 46 in subtype B and at residue 82 in subtype C. The inferred mutational networks for subtype B versus C are significantly different sharing only five constraints on the order of accumulating mutations with mutation at residue 54 as the parental event. The results also suggest that mutations can accumulate along various alternative paths within subtypes, as opposed to a unique total temporal ordering. Beyond HIV drug resistance, the statistical methodology is applicable more generally for the comparison of inferred mutational networks between any two groups.

scholarly journals Why Does It Always Rain on Me? A Spatio-Temporal Analysis of Precipitation in Austria

2016 ◽  
Vol 41 (1) ◽  
Author(s):  
Nikolaus Umlauf ◽  
Georg Mayr ◽  
Jakob Messner ◽  
Achim Zeileis
Keyword(s):  
Temporal Structure ◽  
Temporal Analysis ◽  
Weekend Effect ◽  
Quality Data ◽  
Data Set ◽  
Data Driven Approach ◽  
Spatio Temporal ◽  
Ordered Response ◽  
Additive Regression ◽  
Spatially Varying

It is popular belief that the weather is “bad” more frequently on weekends than on other days of the week and this is often perceived to be associated with an increased chance of rain. In fact, the meteorological literature does report some evidence for such human-induced weekly cycles although these findings are not undisputed. To contribute to this discussion, a modern data-driven approach using structured additive regression modelsis applied to a newly available high-quality data set for Austria. The analysis investigates how an ordered response of rain intensities is influenced by a (potential) weekend effect while adjusting for spatio-temporal structure using spatially varying effects of overall level and seasonality patterns. The underlying data are taken from the HOMSTART project which provides daily precipitation quantities over a period of more than 60 years and a dense netof more than 50 meteorological stations all across Austria.

Short Communication: Discordance in Drug Resistance Mutations Between Blood Plasma and Semen or Rectal Secretions Among Newly Diagnosed HIV-1-Infected Thai Men Who Have Sex with Men

2018 ◽  
Vol 34 (7) ◽  
pp. 626-628
Author(s):  
Akarin Hiransuthikul ◽  
Rapeeporn Wongkanya ◽  
Sunee Sirivichayakul ◽  
Deondara Trachunthong ◽  
Thanthip Sungsing ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Blood Plasma ◽  
Short Communication ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Sex With Men ◽  
Hiv 1

Stratigraphy of architectural elements in a buried volcanic system and implications for hydrocarbon exploration

2017 ◽  
Vol 5 (3) ◽  
pp. SK141-SK159 ◽  
Author(s):  
Alan Patrick Bischoff ◽  
Andrew Nicol ◽  
Mac Beggs
Keyword(s):  
Temporal Distribution ◽  
Large Data ◽  
Sedimentary Basins ◽  
Building Blocks ◽  
Hydrocarbon Exploration ◽  
Coarse Grained ◽  
Data Set ◽  
Volcanic System ◽  
Architectural Elements ◽  
Spatio Temporal

The interaction between magmatism and sedimentation creates a range of petroleum plays at different stratigraphic levels due to the emplacement and burial of volcanoes. This study characterizes the spatio-temporal distribution of the fundamental building blocks (i.e., architectural elements) of a buried volcano and enclosing sedimentary strata to provide insights for hydrocarbon exploration in volcanic systems. We use a large data set of wells and seismic reflection surveys from the offshore Taranaki Basin, New Zealand, compared with outcropping volcanic systems worldwide to demonstrate the local impacts of magmatism on the evolution of the host sedimentary basin and petroleum system. We discover the architecture of Kora volcano, a Miocene andesitic polygenetic stratovolcano that is currently buried by more than 1000 m of sedimentary strata and hosts a subcommercial discovery within volcanogenic deposits. The 22 individual architectural elements have been characterized within three main stratigraphic sequences of the Kora volcanic system. These sequences are referred to as premagmatic (predate magmatism), synmagmatic (defined by the occurrence of intrusive, eruptive, and sedimentary architectural elements), and postmagmatic (degradation and burial of the volcanic structures after magmatism ceased). Potential petroleum plays were identified based on the distribution of the architectural elements and on the geologic circumstances resulting from the interaction between magmatism and sedimentation. At the endogenous level, emplacement of magma forms structural traps, such as drag folds and strata jacked up above intrusions. At the exogenous level, syneruptive, intereruptive, and postmagmatic processes mainly form stratigraphic and paleogeomorphic traps, such as interbedded volcano-sedimentary deposits, and upturned pinchout of volcanogenic and nonvolcanogenic coarse-grained deposits onto the volcanic edifice. Potential reservoirs are located at systematic vertical and lateral distances from eruptive centers. We have determined that identifying the architectural elements of buried volcanoes is necessary for building predictive models and for derisking hydrocarbon exploration in sedimentary basins affected by magmatism.

scholarly journals A8 Epidemiological study of transmission clusters in a local HIV-1 cohort

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Carmen M González Domenech ◽  
Isabel Viciana-Ramos ◽  
Gabriel Sena-Corrales ◽  
Laura Mora Navas ◽  
Guillermo Ojeda ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Demographic Data ◽  
Phylogenetic Reconstruction ◽  
Likelihood Method ◽  
Resistance Mutations ◽  
Primary Resistance ◽  
Number Of Patients ◽  
Sex With Men ◽  
K103n Mutation ◽  
Hiv 1

Abstract Integration of molecular, clinical, and demographic data represents a powerful tool to understand the dynamics of local HIV-1 transmission chains (TCs). The aim of our study was the phylogenetic analysis of the TCs within a HIV-1 cohort and the description of the relevant patient data within a TC. We performed a phylogenetic analysis of 757 sequences from newly HIV-1 diagnosed patients in Málaga (Southern Spain) during the period 2004–15. We used partial pol gene sequences in a preliminary phylogenetic reconstruction using the Neighbour Joining method (MEGA v6.06 program). After eliminating branches with bootstrap values <80 per cent, we constructed a new phylogeny by Maximum likelihood method (FastTree program). We considered as TC any cluster with bootstrap values ≥ 90 per cent. Patient sequences within and outside TCs were compared. Resistance mutations in the protease (PR) and reverse transcriptase (RT) sequences were analyzed using the Stanford algorithm. Four hundred and fifty-one out of 757 patients (59.6%) were grouped into fifty-three TCs, seventeen of them with five or more subjects. The largest number of patients associated within a TC was ninety. Patients younger than 40 years [odds ratio (OR) 1.75, 95% confidence interval (95% CI) 1.2–2.4, P = 0.002], men who have sex with men (MSM) (OR 2.14, 95% CI 1.3–3.2, P < 0.0001), non-Spanish (OR 1.48, 95% CI 1.0–2.1, P = 0.038), with a non-B subtype HIV-1 (OR 3.12, 95% CI 2.0–4.8, P < 0.0001), and presenting primary resistance mutations (OR 14.1, 95% CI 3.1–62.6, P = 0.001) were more likely to be associated within a cluster. Ninety-four out of 118 patients (79.6%) with transmission resistance mutations were included in some TC. The most frequent mutations associated with clusters were T69D/N, L210W, and K219E/Q, for NRTIs, K103N, and G190A/S for NNRTIs, and the I54L/M and L90M mutations for PIs. The prevalence for resistance to NNRTIs in TCs was 13.7 per cent. There were two TCs of rarer non-B subtypes: CRF19_cpx, with twenty-one individuals, sixteen of them (76.2%) with mutation G190A; and CRF51_01B with thirty-nine patients, twenty of them with the K103N mutation. Approximately 60 per cent of newly HIV-1 diagnosed patients were included in a TC. Younger patients, MSM, non-Spanish, with non-B subtype HIV-1 and primary resistance mutations were more likely to belong to a cluster. NNRTI mutations were the most frequent ones among patients in TCs. We observed two TCs represented by infrequent non-B subtypes in our area—CRF19_cpx and CRF51_01B—both of which were associated to the transmission of primary resistance.

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