National molecular surveillance of recently acquired HIV infections in Germany, 2013 to 2014

To enable an up-to-date molecular analysis of human immunodeficiency virus (HIV) genotypes circulating in Germany we have established a surveillance system based on recently acquired HIV infections. New HIV infections are reported to the Robert Koch Institute as a statutory duty for anonymous notification. In 2013 and 2014, a dried serum spot (DSS) sample was received from 6,371 newly diagnosed HIV-cases; their analysis suggested that 1,797 samples originated from a recent infection. Of these, 809 were successfully genotyped in the pol region to identify transmitted drug resistance (TDR) mutations and to determine the HIV-1 subtype. Total TDR was 10.8%, comprising 4.3% with mono-resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 2.6% to non-NRTIs, 3.0% to protease inhibitors and 0.6% and 0.2%, respectively, with dual- and triple-class resistances. HIV-1 subtype B was most prevalent with 77.0%. Non-B infections were identified more often in men and women with heterosexual transmission compared with intravenous drug users or men who have sex with men (79% and 76%, 33%, 12%; all p < 0.05). Non-B subtypes were also more frequently found in patients originating from countries other than Germany (46% vs 14%; p < 0.05) and in patients infected outside of Germany (63% vs 14%; p < 0.05).

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HIV-1 subtype in Scotland: the establishment of a national surveillance system

Epidemiology and Infection ◽

10.1017/s095026880400233x ◽

2004 ◽

Vol 132 (4) ◽

pp. 693-698 ◽

Cited By ~ 10

Author(s):

D. L. YIRRELL ◽

L. SHAW ◽

S. M. BURNS ◽

S. O. CAMERON ◽

M. QUIGG ◽

...

Keyword(s):

United Kingdom ◽

Drug Users ◽

Demographic Data ◽

Risk Groups ◽

Heterosexual Contact ◽

The United Kingdom ◽

Subtype B ◽

Route Of Transmission ◽

Sex With Men ◽

Hiv 1

Historically, subtype B viruses in men who have sex with men (MSM) and injecting drug users (IDU) dominated the HIV epidemic in the United Kingdom, whereas non-B heterosexual infections dominate globally. Heterosexual contact is now the most common route of transmission in the United Kingdom. Here we monitor HIV subtype in Scotland, and link it to origin of infection. HIV-1 sequence was generated from new diagnoses and the subtype thus obtained linked with demographic data. Virus was subtyped from 80% (137/171) of all new diagnoses in Scotland. Of 58 individuals infected by heterosexual contact, 74% (43) harboured non-B viruses, contrasting with 7% (5/68) of those infected by IDU or MSM. Eighty-four per cent of non-Bs (46/55) were probably acquired outside the United Kingdom, but nine individuals probably acquired their non-B infection in the United Kingdom. Non-B subtypes of HIV-1 predominate in recently diagnosed, heterosexually acquired infections in Scotland and are present in all risk groups, even those with no exposure outside the United Kingdom.

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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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Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China

Frontiers in Microbiology ◽

10.3389/fmicb.2021.797771 ◽

2022 ◽

Vol 12 ◽

Author(s):

Bin Zhao ◽

Wei Song ◽

Mingming Kang ◽

Xue Dong ◽

Xin Li ◽

...

Keyword(s):

Network Analysis ◽

Molecular Network ◽

Transmitted Drug Resistance ◽

Newly Diagnosed ◽

Subtype B ◽

Sex With Men ◽

Treat All ◽

Few Data ◽

Drug Resistant Strains ◽

Hiv 1

Since the implementation of the “treat all” policy in China in 2016, there have been few data on the prevalence of transmitted drug resistance (TDR) in China. In this study, we describe TDR in patients newly diagnosed with human immunodeficiency virus (HIV) infection between 2016 and 2019 in Shenyang city, China. Demographic information and plasma samples from all newly reported HIV-infected individuals in Shenyang from 2016 to 2019 were collected. The HIV pol gene was amplified and sequenced for subtyping and TDR. The spread of TDR was analyzed by inferring an HIV molecular network based on pairwise genetic distance. In total, 2,882 sequences including CRF01_AE (2019/2,882, 70.0%), CRF07_BC (526/2,882, 18.3%), subtype B (132/2,882, 4.6%), and other subtypes (205/2,882, 7.1%) were obtained. The overall prevalence of TDR was 9.1% [95% confidence interval (CI): 8.1–10.2%]; the prevalence of TDR in each subtype in descending order was CRF07_BC [14.6% (95% CI: 11.7–18.0%)], subtype B [9.1% (95% CI: 4.8–15.3%)], CRF01_AE [7.9% (95% CI: 6.7–9.1%)], and other sequences [7.3% (95% CI: 4.2–11.8%)]. TDR mutations detected in more than 10 cases were Q58E (n = 51), M46ILV (n = 46), K103N (n = 26), E138AGKQ (n = 25), K103R/V179D (n = 20), and A98G (n = 12). Molecular network analysis revealed three CRF07_BC clusters with TDR [two with Q58E (29/29) and one with K103N (10/19)]; and five CRF01_AE clusters with TDR [two with M46L (6/6), one with A98G (4/4), one with E138A (3/3), and one with K103R/V179D (3/3)]. In the TDR clusters, 96.4% (53/55) of individuals were men who have sex with men (MSM). These results indicate that TDR is moderately prevalent in Shenyang (5–15%) and that TDR strains are mainly transmitted among MSM, providing precise targets for interventions in China.

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HIV subtypes in Scotland, 2000–2006

Epidemiology and Infection ◽

10.1017/s0950268807009545 ◽

2007 ◽

Vol 136 (8) ◽

pp. 1069-1075 ◽

Cited By ~ 4

Author(s):

D. L. YIRRELL ◽

L. SHAW ◽

E. CAMPBELL ◽

S. M. BURNS ◽

S. O. CAMERON ◽

...

Keyword(s):

Drug Users ◽

Geographical Origin ◽

Demographic Data ◽

Risk Groups ◽

Intravenous Drug Users ◽

Subtype B ◽

The Social ◽

Sex With Men ◽

Hiv 1 ◽

Hiv Subtypes

SUMMARYThe purpose of this study was to document the dynamics of HIV-1 subtypes in Scotland over a 6-year period. Viral RNA from all-new diagnoses was amplified by nested PCR and sequenced in the gag and/or env regions. Subtype was assigned by phylogenetic analysis, and aligned with demographic data including likely route and geographical origin of infection. We present data on 80% of all new diagnoses in Scotland between April 2000 and April 2006. Within the background of an expanding epidemic, subtype B predominates in men who have sex with men and intravenous drug users but there is a small but consistent number of UK-acquired infections in these risk groups caused by non-B subtypes. In heterosexuals, non-B subtypes acquired abroad, especially Africa, are still the largest group but again UK-acquired numbers are rising. The social and clinical significance of the spread of non-B subtypes in different ethnic and risk groups remains to be established.

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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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Evaluation of HIV Transmission Clusters among Natives and Foreigners Living in Italy

Viruses ◽

10.3390/v12080791 ◽

2020 ◽

Vol 12 (8) ◽

pp. 791 ◽

Cited By ~ 2

Author(s):

Lavinia Fabeni ◽

Maria Mercedes Santoro ◽

Patrizia Lorenzini ◽

Stefano Rusconi ◽

Nicola Gianotti ◽

...

Keyword(s):

Hiv Transmission ◽

Phylogenetic Analyses ◽

Hiv Infections ◽

Public Health Response ◽

Health Response ◽

Drug Naïve ◽

Recent Diagnosis ◽

Sex With Men ◽

Italian Origin ◽

Hiv 1

We aimed at evaluating the characteristics of HIV-1 molecular transmission clusters (MTCs) among natives and migrants living in Italy, diagnosed between 1998 and 2018. Phylogenetic analyses were performed on HIV-1 polymerase (pol) sequences to characterise subtypes and identify MTCs, divided into small (SMTCs, 2–3 sequences), medium (MMTCs, 4–9 sequences) and large (LMTCs, ≥10 sequences). Among 3499 drug-naïve individuals enrolled in the Italian Cohort Naive Antiretroviral (ICONA) cohort (2804 natives; 695 migrants), 726 (20.8%; 644 natives, 82 migrants) were involved in 228 MTCs (6 LMTCs, 36 MMTCs, 186 SMTCs). Migrants contributed 14.4% to SMTCs, 7.6% to MMTCs and 7.1% to LMTCs, respectively. HIV-1 non-B subtypes were found in 51 MTCs; noteworthy was that non-B infections involved in MTCs were more commonly found in natives (n = 47) than in migrants (n = 4). Factors such as Italian origin, being men who have sex with men (MSM), younger age, more recent diagnosis and a higher CD4 count were significantly associated with MTCs. Our findings show that HIV-1 clustering transmission among newly diagnosed individuals living in Italy is prevalently driven by natives, mainly MSM, with a more recent diagnosis and frequently infected with HIV-1 non-B subtypes. These results can contribute to monitoring of the HIV epidemic and guiding the public health response to prevent new HIV infections.

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Amino Acid Deletions in p6Gag Domain of HIV-1 CRF07_BC Ameliorate Galectin-3 Mediated Enhancement in Viral Budding

International Journal of Molecular Sciences ◽

10.3390/ijms21082910 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2910 ◽

Cited By ~ 1

Author(s):

Wen-Hung Wang ◽

Chun-Sheng Yeh ◽

Chih-Yen Lin ◽

Ruei-Yu Yuan ◽

Aspiro Nayim Urbina ◽

...

Keyword(s):

Amino Acid ◽

Drug Users ◽

Potential Effect ◽

Promoting Effect ◽

Viral Budding ◽

Subtype B ◽

Infectious Clones ◽

Galectin 3 ◽

Hiv 1

HIV-1 CRF07_BC is a recombinant virus with amino acid (a.a.) deletions in p6Gag, which are overlapped with the Alix-binding domain. Galectin-3 (Gal3), a β-galactose binding lectin, has been reported to interact with Alix and regulate HIV-1 subtype B budding. This study aims to evaluate the role of Gal3 in HIV-1 CRF07_BC infection and the potential effect of a.a. deletions on Gal3-mediated regulation. A total of 38 HIV-1+ injecting drug users (IDUs) were enrolled in the study. Viral characterization and correlation of Gal3 were validated. CRF07_BC containing 7 a.a. deletions and wild-type in the p6Gag (CRF07_BC-7d and -wt) were isolated and infectious clones were generated. Viral growth kinetic and budding assays using Jurkat-CCR5/Jurkat-CCR5-Gal3 cells infected with CRF07_BC were performed. Results indicate that 69.4% (25/38) of the recruited patients were identified as CRF07_BC, and CRF07_BC-7d was predominant. Slow disease progression and significantly higher plasma Gal3 were noted in CRF07_BC patients (p < 0.01). Results revealed that CRF07_BC infection resulted in Gal3 expression, which was induced by Tat. Growth dynamic and budding assays indicated that Gal3 expression in Jurkat-CCR5 cells significantly enhanced CRF07_BC-wt replication and budding (p < 0.05), while the promoting effect was ameliorated in CRF07_BC-7d. Co-immunoprecipitation found that deletions in the p6Gag reduced Gal-3-mediated enhancement of the Alix–Gag interaction.

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Reconstructing the Dissemination Dynamics of the Major HIV-1 Subtype B Non-Pandemic Lineage Circulating in Brazil

Viruses ◽

10.3390/v11100909 ◽

2019 ◽

Vol 11 (10) ◽

pp. 909

Author(s):

Ighor Arantes ◽

Myuki Alfaia Esashika Crispim ◽

Mônica Nogueira da Guarda Reis ◽

Mariane Martins Araújo Stefani ◽

Gonzalo Bello

Keyword(s):

Hiv Infections ◽

Spreading Rate ◽

South American ◽

Caribbean Islands ◽

Subtype B ◽

Demographic Dynamics ◽

Immunodeficiency Virus ◽

Northern Brazil ◽

Hiv 1

Non-pandemic variants of the Human Immunodeficiency Virus Type 1 (HIV-1) subtype B accounts for a significant fraction of HIV infections in several Caribbean islands, Northeastern South American countries and the Northern Brazilian states of Roraima and Amazonas. In this paper, we used a comprehensive dataset of HIV-1 subtype B pol sequences sampled in Amazonas and Roraima between 2007 and 2017 to reconstruct the phylogeographic and demographic dynamics of the major HIV-1 subtype B non-pandemic Brazilian lineage, designated as BCAR-BR-I. Our analyses revealed that its origin could be traced to one of many viral introductions from French Guiana and Guyana into Northern Brazil, which probably occurred in the state of Amazonas around the late 1970s. The BCAR-BR-I clade was rapidly disseminated from Amazonas to Roraima, and the epidemic grew exponentially in these Northern Brazilian states during the 1980s and 1990s, coinciding with a period of economic and fast population growth in the region. The spreading rate of the BCAR-BR-I clade, however, seems to have slowed down since the early 2000s, despite the continued expansion of the HIV-1 epidemic in this region in the last decade.

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