The changing HIV-1 genetic characteristics and transmitted drug resistance among recently infected population in Yunnan, China

AbstractMultiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (15.8%), CRF07_BC (14.4%), subtype C (2.7%), CRF55_01B (0.7%), subtype B (0.3%) and CRF64_BC (0.3%). CRF08_BC and CRF01_AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08_BC, URFs, CRF01_AE and CRF07_BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01_AE, CRF07_BC and CRF08_BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially during 1991–1999 and 1994–1999, respectively. The EPS for CRF08_BC underwent two exponential growth phases in 1994–1998 and 2001–2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.

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Increase in HIV-1-transmitted drug resistance among ART-naïve youths at the China-Myanmar border during 2009 ~ 2017

BMC Infectious Diseases ◽

10.1186/s12879-021-05794-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yibo Ding ◽

Min Chen ◽

Jibao Wang ◽

Yuecheng Yang ◽

Yi Feng ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Cd4 Count ◽

Transmitted Drug Resistance ◽

Subtype C ◽

Reverse Transcriptase Inhibitors ◽

Recombination Hotspots ◽

Subtype B ◽

Sex With Men ◽

Hiv 1

Abstract Background HIV-transmitted drug resistance (TDR) is found in antiretroviral therapy (ART)-naïve populations infected with HIV-1 with TDR mutations and is important for guiding future first- and second-line ART regimens. We investigated TDR and its effect on CD4 count in ART-naïve youths from the China-Myanmar border near the Golden Triangle to better understand TDR and effectively guide ART. Methods From 2009 to 2017, 10,832 HIV-1 infected individuals were newly reported along the Dehong border of China, 573 ART-naïve youths (16 ~ 25 y) were enrolled. CD4 counts were obtained from whole blood samples. HIV pol gene sequences were amplified from RNA extracted from plasma. The Stanford REGA program and jpHMM recombination prediction tool were used to determine genotypes. TDR mutations (TDRMs) were analyzed using the Stanford Calibrated Population Resistance tool. Results The most common infection route was heterosexuals (70.51%), followed by people who inject drugs (PWID, 19.20%) and men who have sex with men (MSM) (8.90%). The distribution of HIV genotypes mainly included the unique recombinant form (URF) (44.08%), 38.68% were CRFs, 13.24% were subtype C and 4.04% were subtype B. The prevalence of TDR increased significantly from 2009 to 2017 (3.48 to 9.48%) in ART-naïve youths (4.00 to 13.16% in Burmese subjects, 3.33 to 5.93% in Chinese subjects), and the resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 3.49, 2.62, and 0.52%, respectively. Most (94.40%, n = 34) of HIV-1-infected patients with TDRM had mutation that conferred resistance to a single drug class. The most common mutations Y181I/C and K103N, were found in 7 and 9 youths, respectively. The mean CD4 count was significantly lower among individuals with TDRMs (373/mm3 vs. 496/mm3, p = 0.013). Conclusions The increase in the prevalence of HIV-1 TDR increase and a low CD4 count of patients with TDRMs in the China-Myanmar border suggests the need for considering drug resistance before initiating ART in HIV recombination hotspots.

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Epidemiology and Transmitted HIV-1 Drug Resistance among Treatment-Naïve Individuals in Israel, 2010–2018

Viruses ◽

10.3390/v14010071 ◽

2021 ◽

Vol 14 (1) ◽

pp. 71

Author(s):

Tali Wagner ◽

Neta S. Zuckerman ◽

Tami Halperin ◽

Daniel Chemtob ◽

Itzchak Levy ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Sub Saharan Africa ◽

Resistance Testing ◽

Transmitted Drug Resistance ◽

Resistance Mutations ◽

Subtype C ◽

Reverse Transcriptase Inhibitors ◽

Subtype B ◽

Hiv 1

Despite the low prevalence of HIV-1 in Israel, continuous waves of immigration may have impacted the local epidemic. We characterized all people diagnosed with HIV-1 in Israel in 2010–2018. The demographics and clinical data of all individuals (n = 3639) newly diagnosed with HIV-1 were retrieved. Subtypes, transmitted drug-resistance mutations (TDRM), and phylogenetic relations, were determined in >50% of them. In 39.1%, HIV-1 transmission was through heterosexual contact; 34.3% were men who have sex with men (MSM); and 10.4% were people who inject drugs. Many (>65%) were immigrants. Israeli-born individuals were mostly (78.3%) MSM, whereas only 9% of those born in Sub-Saharan Africa (SSA), Eastern Europe and Central Asia (EEU/CA), were MSM. The proportion of individuals from SSA decreased through the years 2010–2018 (21.1% in 2010–2012; 16.8% in 2016–2018) whereas those from EEU/CA increased significantly (21% in 2010–2012; 27.8% in 2016–2018, p < 0.001). TDRM were identified in 12.1%; 3.7, 3.3 and 6.6% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively, with the overall proportion remaining stable in the studied years. None had integrase TDRM. Subtype B was present in 43.9%, subtype A in 25.2% (A6 in 22.8 and A1 in 2.4%) and subtype C in 17.1% of individuals. Most MSM had subtype B. Subtype C carriers formed small clusters (with one unexpected MSM cluster), A1 formed a cluster mainly of locally-born patients with NNRTI mutations, and A6 formed a looser cluster of individuals mainly from EEU. Israelis, <50 years old, carrying A1, had the highest risk for having TDRM. In conclusion, an increase in immigrants from EEU/CA and a decrease in those from SSA characterized the HIV-1 epidemic in 2010–2018. Baseline resistance testing should still be recommended to identify TDRM, and improve surveillance and care.

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Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil

International Journal of Molecular Sciences ◽

10.3390/ijms22105304 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5304

Author(s):

Ana Santos-Pereira ◽

Vera Triunfante ◽

Pedro M. M. Araújo ◽

Joana Martins ◽

Helena Soares ◽

...

Keyword(s):

Drug Resistance ◽

People Living With Hiv ◽

Resistance Mutations ◽

Subtype C ◽

Viral Loads ◽

Drug Resistance Mutations ◽

Subtype B ◽

Low Prevalence ◽

Living With Hiv ◽

Hiv 1

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

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Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018

BMC Infectious Diseases ◽

10.1186/s12879-021-06312-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhen Wang ◽

Bin Zhao ◽

Minghui An ◽

Wei Song ◽

Xue Dong ◽

...

Keyword(s):

Drug Resistance ◽

Hiv Infection ◽

Northeast China ◽

Transmitted Drug Resistance ◽

Newly Diagnosed ◽

Resistance Mutations ◽

Shenyang City ◽

Subtype B ◽

Recent Hiv Infection ◽

Hiv 1

Abstract Background To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. Methods Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. Results A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). Conclusions The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.

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Diversity of HIV-1 subtypes and transmitted drug-resistance mutations among minority HIV-1 variants in a Turkish cohort

Current HIV Research ◽

10.2174/1570162x19666211119111740 ◽

2021 ◽

Vol 19 ◽

Author(s):

Rabia Can Sarinoglu ◽

Uluhan Sili ◽

Ufuk Hasdemir ◽

Burak Aksu ◽

Guner Soyletir ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Transcriptase Inhibitor ◽

Transmitted Drug Resistance ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Subtype B ◽

Treatment Naïve ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1

Background: The World Health Organization (WHO) recommends the surveillance of transmitted drug resistance mutations (TDRMs) to ensure the effectiveness and sustainability of HIV treatment programs. Objective: Our aim was to determine the TDRMs and evaluate the distribution of HIV-1 subtypes using and compared next-generation sequencing (NGS) and Sanger-based sequencing (SBS) in a cohort of 44 antiretroviral treatment-naïve patients. Methods: All samples that were referred to the microbiology laboratory for HIV drug resistance analysis between December 2016 and February 2018 were included in the study. After exclusions, 44 treatment-naive adult patients with a viral load of >1000 copies/mL were analyzed. DNA sequencing for reverse transcriptase and protease regions was performed using both DeepChek ABL single round kit and Sanger-based ViroSeq HIV-1 Genotyping System. The mutations and HIV-1 subtypes were analyzed using the Stanford HIVdb version 8.6.1 Genotypic Resistance software, and TDRMs were assessed using the WHO surveillance drug-resistance mutation database. HIV-1 subtypes were confirmed by constructing a maximum-likelihood phylogenetic tree using Los Alamos IQ-Tree software. Results: NGS identified nucleos(t)ide reverse transcriptase inhibitor (NRTI)-TDRMs in 9.1% of the patients, non-nucleos(t)ide reverse transcriptase inhibitor (NNRTI)-TDRMs in 6.8% of the patients, and protease inhibitor (PI)-TDRMs in 18.2% of the patients at a detection threshold of ≥1%. Using SBS, 2.3% and 6.8% of the patients were found to have NRTI- and NNRTI-TDRMs, respectively, but no major PI mutations were detected. M41L, L74I, K65R, M184V, and M184I related to NRTI, K103N to NNRTI, and N83D, M46I, I84V, V82A, L24I, L90M, I54V to the PI sites were identified using NGS. Most mutations were found in low-abundance (frequency range: 1.0% - 4.7%) HIV-1 variants, except M41L and K103N. The subtypes of the isolates were found as follows; 61.4% subtype B, 18.2% subtype B/CRF02_AG recombinant, 13.6% subtype A, 4.5% CRF43_02G, and 2.3% CRF02_AG. All TDRMs, except K65R, were detected in HIV-1 subtype B isolates.. Conclusion: The high diversity of protease site TDRMs in the minority HIV-1 variants and prevalence of CRFs were remarkable in this study. All minority HIV-1 variants were missed by conventional sequencing. TDRM prevalence among minority variants appears to be decreasing over time at our center.

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Transmitted drug resistance mutations and subtype diversity among HIV-1 sero-positive voluntary blood donors in Accra, Ghana

10.21203/rs.3.rs-21810/v1 ◽

2020 ◽

Author(s):

Billal Musah Obeng ◽

Evelyn Yayra Bonney ◽

Lucy Asamoah-Akuoko ◽

Nicholas Israel Nii-Trebi ◽

Gifty Mawuli ◽

...

Keyword(s):

Drug Resistance ◽

Blood Donors ◽

Transmitted Drug Resistance ◽

Nucleotide Sequencing ◽

Plasma Samples ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Subtype B ◽

Major Drug ◽

Hiv 1

Abstract Background: Detection of HIV-1 transmitted drug resistance (TDR) and subtype diversity (SD) are public health strategies to assess current HIV-1 regimen and ensure effective therapeutic outcomes of ART among HIV-1 patients. Globally, limited data exist on TDR and SD among blood donors. In this study, drug resistance mutations and subtype diversity among HIV-1 sero-positive blood donors in Accra, Ghana was characterized.Methods: Purposive sampling method was used to collect 81 HIV sero-positive blood samples from the Southern Area Blood Center and confirmed by serology as HIV-1 and/or HIV-2. Viral RNA was only extracted from plasma samples confirmed as HIV-1 positive. Complementary DNA (cDNA) was synthesized using the RNA as a template and subsequently amplified by nested PCR with specific primers. The expected products were verified, purified and sequenced. Neighbor-joining tree with the Kimura’s 2-parameter distances was generated with the RT sequences using Molecular Evolutionary Genetic Analysis version 6.0 (MEGA 6.0).Results: Out of the 81 plasma samples, 60 (74%) were confirmed as HIV-1 sero-positive by INNO-LIA HIVI/II Score kit with no HIV-2 and dual HIV-1/2 infections. The remaining samples, 21 (26%) were confirmed as HIV sero-negative. Of the 60 confirmed positive samples, (32) 53% and (28) 50% were successfully amplified in the RT and PR genes respectively. Nucleotide sequencing of amplified samples revealed the presence of major drug resistance mutations in two (2) samples; E138A in one sample and another with K65R. HIV-1 Subtypes including subtypes A, B, CRF02_AG and CRF09_cpx were found. Conclusion: This study found major drug resistance mutations, E138A and K65R in the RT gene that confer high level resistance to most NNRTIs and NRTI respectively. CRF02_AG was most predominant, the recorded percentage of subtype B and the evolutionary relationship inferred by phylogenetic analysis suggest possible subtype importation. The data obtained would inform the selection of drugs for ART initiation to maximize therapeutic options in drug-naïve HIV-1 patients in Ghana.

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

10.1101/2020.09.25.312942 ◽

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.

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HIV-1 subtype variability and transmitted drug resistance in a culturally diverse population in Western Sydney, New South Wales, Australia

Sexual Health ◽

10.1071/sh20013 ◽

2020 ◽

Vol 17 (4) ◽

pp. 377

Author(s):

Daniel Richardson ◽

Hubert Chan ◽

Rohan Bopage ◽

David A. Lewis ◽

Shailendra Sawleshwarkar ◽

...

Keyword(s):

Drug Resistance ◽

Culturally Diverse ◽

Hiv Transmission ◽

Transmitted Drug Resistance ◽

Diverse Population ◽

Subtype B ◽

Sexually Transmissible Infections ◽

Treatment Naïve ◽

Relative Prevalence ◽

Hiv 1

Abstract Background Transmitted human immunodeficiency virus type 1 (HIV-1) drug resistance (TDR) is an important contributor to antiretroviral treatment failure, and is associated with HIV-1 transmission among men who have sex with men (MSM), non-MSM clusters and individuals diagnosed with concurrent sexually transmissible infections (STI). Western Sydney has a culturally diverse population, with a high proportion of non-Australian-born individuals. This study describes the prevalence of TDR and non-B HIV-1 subtypes in a clinic-based population. Methods: A clinic database was examined for all newly diagnosed treatment-naïve HIV-1 patients and information on their HIV-1 resistance and subtype, demographics including country of birth and diagnosis of a bacterial sexually transmissible infection was collected. Results: Data were available from 74/79 individuals (62 cis-male, 16 cis-female and 1 transgender woman). Of the 74 genotypes, the prevalence of non-B subtypes and TDR was 43/74 (58%; 95%CI = 46.9–69.3) and 14/74 (19%; 95%CI = 10.0 to 27.8). It was also found that 30/79 (38%) had a concurrent bacterial STI. TDR was associated with subtype B infection (OR 3.53; 95%CI = 1.41–8.82; P = 0.007) and being born in Australia (OR 12.0; 95%CI = 2.45–58.86; P = 0.002). Conclusion: The relative prevalence of non-B HIV-1 subtypes and TDR is higher in Western Sydney than in the rest of Australia. TDR is associated with subtype B HIV-1 and being Australian born, suggesting ongoing local transmission. This highlights the diversity of the HIV epidemic locally and the need for interventions to prevent ongoing HIV transmission.

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Molecular Genetics and the Incidence of Transmitted Drug Resistance Among Pre-Treatment HIV-1 Infected Patients in the Eastern Cape, South Africa

Current HIV Research ◽

10.2174/1570162x17666191004093433 ◽

2019 ◽

Vol 17 (5) ◽

pp. 335-342

Author(s):

Tennison Onoriode Digban ◽

Benson Chucks Iweriebor ◽

Larry Chikwelu Obi ◽

Uchechuwku Nwodo ◽

Anthony Ifeanyi Okoh

Keyword(s):

South Africa ◽

Drug Resistance ◽

Transmitted Drug Resistance ◽

Eastern Cape ◽

Resistance Mutations ◽

Subtype C ◽

Drug Resistance Mutations ◽

Combined Antiretroviral Therapy ◽

Pre Treatment ◽

Hiv 1

Background: Transmitted drug resistance (TDR) remains a significant threat to Human immunodeficiency virus (HIV) infected patients that are not exposed to antiretroviral treatment. Although, combined antiretroviral therapy (cART) has reduced deaths among infected individuals, emergence of drug resistance is gradually on rise. Objective: To determine the drug resistance mutations and subtypes of HIV-1 among pre-treatment patients in the Eastern Cape of South Africa. Methods: Viral RNA was extracted from blood samples of 70 pre-treatment HIV-1 patients while partial pol gene fragment amplification was achieved with specific primers by RT-PCR followed by nested PCR and positive amplicons were sequenced utilizing ABI Prism 316 genetic sequencer. Drug resistance mutations (DRMs) analysis was performed by submitting the generated sequences to Stanford HIV drug resistance database. Results: Viral DNA was successful for 66 (94.3%) samples of which 52 edited sequences were obtained from the protease and 44 reverse transcriptase sequences were also fully edited. Four major protease inhibitor (PI) related mutations (I54V, V82A/L, L76V and L90M) were observed in seven patients while several other minor and accessory PIs were also identified. A total of 11(25.0%) patients had NRTIs related mutations while NNRTIs were observed among 14(31.8%) patients. K103N/S, V106M and M184V were the most common mutations identified among the viral sequences. Phylogenetic analysis of the partial pol gene indicated all sequences clustered with subtype C. Conclusions: This study indicates that HIV-1 subtype C still predominates and responsible for driving the epidemic in the Eastern Cape of South Africa with slow rise in the occurrence of transmitted drug resistance.

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Identification of a New HIV-1 BC Intersubtype Circulating Recombinant Form (CRF108_BC) in Spain

Viruses ◽

10.3390/v13010093 ◽

2021 ◽

Vol 13 (1) ◽

pp. 93

Author(s):

Javier E. Cañada ◽

Elena Delgado ◽

Horacio Gil ◽

Mónica Sánchez ◽

Sonia Benito ◽

...

Keyword(s):

Phylogenetic Analyses ◽

Basque Country ◽

Recent Common Ancestor ◽

Subtype C ◽

Northern Spain ◽

Most Recent Common Ancestor ◽

Phylogenetic Cluster ◽

Subtype B ◽

Definition Of ◽

Hiv 1

The extraordinary genetic variability of human immunodeficiency virus type 1 (HIV-1) group M has led to the identification of 10 subtypes, 102 circulating recombinant forms (CRFs) and numerous unique recombinant forms. Among CRFs, 11 derived from subtypes B and C have been identified in China, Brazil, and Italy. Here we identify a new HIV-1 CRF_BC in Northern Spain. Originally, a phylogenetic cluster of 15 viruses of subtype C in protease-reverse transcriptase was identified in an HIV-1 molecular surveillance study in Spain, most of them from individuals from the Basque Country and heterosexually transmitted. Analyses of near full-length genome sequences from six viruses from three cities revealed that they were BC recombinant with coincident mosaic structures different from known CRFs. This allowed the definition of a new HIV-1 CRF designated CRF108_BC, whose genome is predominantly of subtype C, with four short subtype B fragments. Phylogenetic analyses with database sequences supported a Brazilian ancestry of the parental subtype C strain. Coalescent Bayesian analyses estimated the most recent common ancestor of CRF108_BC in the city of Vitoria, Basque Country, around 2000. CRF108_BC is the first CRF_BC identified in Spain and the second in Europe, after CRF60_BC, both phylogenetically related to Brazilian subtype C strains.

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