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Viruses
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HIV Molecular Epidemiology for Prevention 2020
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HIV Molecular Epidemiology for Prevention 2020

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 46666

Special Issue Editors

Mr. William M. M. Switzer

E-Mail Website
Guest Editor
Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
Interests: emerging retroviruses; zoonotic retrovirus infections; molecular epidemiology of retrovirus infections; retrovirus evolution; retrovirus diagnostics; phylodynamics; transmission networks; bioinformatics; HIV prevention
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Dimitrios Paraskevis

E-Mail Website
Guest Editor
Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
Interests: epidemiology; molecular epidemiology; public health; virology; AIDS/HIV; STIs; hepatitis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The molecular epidemiology of infectious diseases is being transformed by the increasing availability of pathogen nucleotide sequence data from advances in sequencing technologies and their global availability. Molecular sequences combined with epidemiologic data are critical for understanding pathogen emergence, transmission histories, identifying reservoirs and new infections, preventing onward transmission, monitoring disease progression, and linking infected persons to treatment and care. In 2017, WHO estimates about 36.9 million people were living with HIV globally. Of those, almost 940,000 died from AIDS-related illnesses and approximately 75% were unaware of their HIV status. For HIV, drug resistance monitoring is the standard of care for new diagnoses, and testing is routinely available at commercial laboratories or frequently done for research studies. More recently, these HIV polymerase sequences are being used to identify persons with genetically similar strains, characterize transmission clusters and dynamics, and recognize clusters with rapid and active transmission, all of which permit focused public health interventions of limited resources to those persons and places with the highest risk of new infections. In the US, rapidly detecting and responding to clusters and outbreaks is a key pillar of the President’s 2019 intitiative “Ending the HIV Epidemic” in the next decade. This goal is consistent with the WHO target of ending the HIV/AIDS epidemic by 2030. Transmission clusters can be identified using network and phylogenetic analyses of molecular sequences, or combinations of both, and bioinformatics methods are used or being developed to determine timing of infection, time–space clusters, the prediction of cluster growth and spread, and the modeling of transmission dynamics and targeted prevention strategies.

This Special Issue aims to provide new insights and advances in the molecular epidemiology of HIV infection, including how molecular epidemiology is being used for surveillance, understanding transmission dynamics (patterns, order, and probability), the spread of HIV locally and globally, phylodynamics, outbreak and cluster detection, transmission networks, the use of partial and whole genomes, ultradeep sequencing for molecular epidemiology, transmitted drug resistance, and the modeling of transmission clusters and targeted prevention strategies. We cordially invite you to contribute original papers and review articles on these and related topics to highlight recent advances in molecular epidemiologic methods used to study HIV transmission and prevention.

Dr. William M. M. Switzer
Dr. Dimitrios Paraskevis
Guest Editors

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Keywords

  • human immunodeficiency virus (HIV)
  • molecular epidemiology
  • transmission dynamics
  • transmission networks and clusters
  • cluster detection
  • phylogenetic analysis
  • phylodynamics
  • drug resistance testing
  • sequence analysis
  • subtypes
  • quasispecies
  • public health response
  • risk factors
  • persons who inject drugs
  • interventions
  • pre- and post-exposure prophylaxis
  • modeling
  • prevention and care
  • partner services
  • contact tracing
  • disease surveillance
  • co-infections
  • data integration and visualization
  • bioinformatics

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15 pages, 1401 KiB  
Article
Dating the Origin and Estimating the Transmission Rates of the Major HIV-1 Clusters in Greece: Evidence about the Earliest Subtype A1 Epidemic in Europe
by Stefanos Limnaios, Evangelia Georgia Kostaki, Georgios Adamis, Myrto Astriti, Maria Chini, Nikos Mangafas, Marios Lazanas, Stavros Patrinos, Simeon Metallidis, Olga Tsachouridou, Vasileios Papastamopoulos, Eleni Kakalou, Dimitrios Chatzidimitriou, Anastasia Antoniadou, Antonios Papadopoulos, Mina Psichogiou, Dimitrios Basoulis, Maria Gova, Dimitrios Pilalas, Dimitra Paraskeva, Georgios Chrysos, Vasileios Paparizos, Sofia Kourkounti, Helen Sambatakou, Vasileios Bolanos, Nikolaos V. Sipsas, Malvina Lada, Emmanouil Barbounakis, Evrikleia Kantzilaki, Periklis Panagopoulos, Efstratios Maltezos, Stelios Drimis, Vana Sypsa, Pagona Lagiou, Gkikas Magiorkinis, Angelos Hatzakis, Lemonia Skoura and Dimitrios Paraskevisadd Show full author list remove Hide full author list
Viruses 2022, 14(1), 101; https://doi.org/10.3390/v14010101 - 6 Jan 2022
Cited by 3 | Viewed by 2162
Abstract
Our aim was to estimate the date of the origin and the transmission rates of the major local clusters of subtypes A1 and B in Greece. Phylodynamic analyses were conducted in 14 subtype A1 and 31 subtype B clusters. The earliest dates of [...] Read more.
Our aim was to estimate the date of the origin and the transmission rates of the major local clusters of subtypes A1 and B in Greece. Phylodynamic analyses were conducted in 14 subtype A1 and 31 subtype B clusters. The earliest dates of origin for subtypes A1 and B were in 1982.6 and in 1985.5, respectively. The transmission rate for the subtype A1 clusters ranged between 7.54 and 39.61 infections/100 person years (IQR: 9.39, 15.88), and for subtype B clusters between 4.42 and 36.44 infections/100 person years (IQR: 7.38, 15.04). Statistical analysis revealed that the average difference in the transmission rate between the PWID and the MSM clusters was 6.73 (95% CI: 0.86 to 12.60; p = 0.026). Our study provides evidence that the date of introduction of subtype A1 in Greece was the earliest in Europe. Transmission rates were significantly higher for PWID than MSM clusters due to the conditions that gave rise to an extensive PWID HIV-1 outbreak ten years ago in Athens, Greece. Transmission rate can be considered as a valuable measure for public health since it provides a proxy of the rate of epidemic growth within a cluster and, therefore, it can be useful for targeted HIV prevention programs. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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15 pages, 2047 KiB  
Article
Large Evolutionary Rate Heterogeneity among and within HIV-1 Subtypes and CRFs
by Arshan Nasir, Mira Dimitrijevic, Ethan Romero-Severson and Thomas Leitner
Viruses 2021, 13(9), 1689; https://doi.org/10.3390/v13091689 - 26 Aug 2021
Cited by 10 | Viewed by 2775
Abstract
HIV-1 is a fast-evolving, genetically diverse virus presently classified into several groups and subtypes. The virus evolves rapidly because of an error-prone polymerase, high rates of recombination, and selection in response to the host immune system and clinical management of the infection. The [...] Read more.
HIV-1 is a fast-evolving, genetically diverse virus presently classified into several groups and subtypes. The virus evolves rapidly because of an error-prone polymerase, high rates of recombination, and selection in response to the host immune system and clinical management of the infection. The rate of evolution is also influenced by the rate of virus spread in a population and nature of the outbreak, among other factors. HIV-1 evolution is thus driven by a range of complex genetic, social, and epidemiological factors that complicates disease management and prevention. Here, we quantify the evolutionary (substitution) rate heterogeneity among major HIV-1 subtypes and recombinants by analyzing the largest collection of HIV-1 genetic data spanning the widest possible geographical (100 countries) and temporal (1981–2019) spread. We show that HIV-1 substitution rates vary substantially, sometimes by several folds, both across the virus genome and between major subtypes and recombinants, but also within a subtype. Across subtypes, rates ranged 3.5-fold from 1.34 × 10−3 to 4.72 × 10−3 in env and 2.3-fold from 0.95 × 10−3 to 2.18 × 10−3 substitutions site−1 year−1 in pol. Within the subtype, 3-fold rate variation was observed in env in different human populations. It is possible that HIV-1 lineages in different parts of the world are operating under different selection pressures leading to substantial rate heterogeneity within and between subtypes. We further highlight how such rate heterogeneity can complicate HIV-1 phylodynamic studies, specifically, inferences on epidemiological linkage of transmission clusters based on genetic distance or phylogenetic data, and can mislead estimates about the timing of HIV-1 lineages. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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11 pages, 792 KiB  
Article
Identification, Genetic Characterization and Validation of Highly Diverse HIV-1 Viruses for Reference Panel Development
by Jiangqin Zhao, Hanxia Huang, Sherwin Lee, Viswanath Ragupathy, Santanu Biswas, Christelle Mbondji-wonje, Xue Wang, Alex Jiang and Indira Hewlett
Viruses 2021, 13(7), 1417; https://doi.org/10.3390/v13071417 - 20 Jul 2021
Cited by 2 | Viewed by 2553
Abstract
The continued diversification of HIV poses potentially significant challenges to HIV diagnostics and therapeutics. The dynamic evolution of emerging variants is highlighted in countries such as Cameroon in West Central Africa, where all known subtypes and circulating recombinant forms (CRFs) have been shown [...] Read more.
The continued diversification of HIV poses potentially significant challenges to HIV diagnostics and therapeutics. The dynamic evolution of emerging variants is highlighted in countries such as Cameroon in West Central Africa, where all known subtypes and circulating recombinant forms (CRFs) have been shown to be prevalent. We obtained several hundred HIV-positive plasma and viruses from this region for characterization and identification of highly divergent HIV strains. A total of 163 viral strains were cultured to high titers and high volumes using donor peripheral blood mononuclear cells (PBMCs). Initially, 101 viruses representing 59 strains were well characterized and categorized. Results showed that the viral load (VL) range was 0.36–398.9 × 107 copies/mL, p24 values was 0.2–1134 ng/mL. Phylogenetic analysis of thirty-six near full-length HIV-1 genomic sequences demonstrated that most recombinants were highly diverse CRF02 containing unique recombinant forms (URFs). There were seven viral isolates identified as pure subtype/sub-subtypes (F2, A1, G, and D), six as CRFs (CRF06, CRF18, and CRF22), and ten as URFs. These extensively characterized reagents reflect the current dynamic and complex HIV epidemic in Cameroon and provide valuable insights into the potential phylogenetic evolutionary trend of global HIV molecular epidemiology in the future. These materials may be useful for development of HIV validation and reference panels to evaluate the performance of serologic antigen and nucleic acid assays for their ability to detect and quantitate highly divergent HIV strains. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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9 pages, 1549 KiB  
Article
Genetic Characterization of a New HIV-1 Sub-Subtype A in Cabo Verde, Denominated A8
by Rayana Katylin Mendes Da Silva, Isabel Inês Monteiro de Pina Araujo, Karine Venegas Maciera, Mariza Gonçalves Morgado and Monick Lindenmeyer Guimarães
Viruses 2021, 13(6), 1093; https://doi.org/10.3390/v13061093 - 8 Jun 2021
Cited by 11 | Viewed by 2478
Abstract
Previous molecular characterization of Human immunodeficiency virus (HIV-1) samples from Cabo Verde pointed out a vast HIV-1 pol diversity, with several subtypes and recombinant forms, being 5.2% classified as AU-pol. Thus, the aim of the present study was to improve the [...] Read more.
Previous molecular characterization of Human immunodeficiency virus (HIV-1) samples from Cabo Verde pointed out a vast HIV-1 pol diversity, with several subtypes and recombinant forms, being 5.2% classified as AU-pol. Thus, the aim of the present study was to improve the characterization of these AU sequences. The genomic DNA of seven HIV-1 AU pol-infected individuals were submitted to four overlapping nested-PCR fragments aiming to compose the full-length HIV-1 genome. The final classification was based on phylogenetic trees that were generated using the maximum likelihood and bootscan analysis. The genetic distances were calculated using Mega 7.0 software. Complete genome amplification was possible for two samples, and partial genomes were obtained for the other five. These two samples grouped together with a high support value, in a separate branch from the other sub-subtypes A and CRF26_A5U. No recombination was verified at bootscan, leading to the classification of a new sub-subtype A. The intragroup genetic distance from the new sub-subtype A at a complete genome was 5.2%, and the intergroup genetic varied from 8.1% to 19.0% in the analyzed fragments. Our study describes a new HIV-1 sub-subtype A and highlights the importance of continued molecular surveillance studies, mainly in countries with high HIV molecular diversity. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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15 pages, 11029 KiB  
Article
Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance
by Soo-Yon Rhee, Philip L. Tzou and Robert W. Shafer
Viruses 2021, 13(5), 879; https://doi.org/10.3390/v13050879 - 11 May 2021
Cited by 12 | Viewed by 2386
Abstract
In 2009, a list of nonpolymorphic HIV-1 drug resistance mutations (DRMs), called surveillance DRMs (SDRMs), was created to monitor transmitted drug resistance (TDR). Since 2009, TDR increased and antiretroviral therapy (ART) practices changed. We examined the changing prevalence of SDRMs and identified candidate [...] Read more.
In 2009, a list of nonpolymorphic HIV-1 drug resistance mutations (DRMs), called surveillance DRMs (SDRMs), was created to monitor transmitted drug resistance (TDR). Since 2009, TDR increased and antiretroviral therapy (ART) practices changed. We examined the changing prevalence of SDRMs and identified candidate SDRMs defined as nonpolymorphic DRMs present on ≥ 1 expert DRM list and in ≥0.1% of ART-experienced persons. Candidate DRMs were further characterized according to their association with antiretrovirals and changing prevalence. Among NRTI-SDRMs, tenofovir-associated mutations increased in prevalence while thymidine analog mutations decreased in prevalence. Among candidate NRTI-SDRMs, there were six tenofovir-associated mutations including three which increased in prevalence (K65N, T69deletion, K70G/N/Q/T). Among candidate NNRTI-SDRMs, six that increased in prevalence were associated with rilpivirine (E138K/Q, V179L, H221Y) or doravirine (F227C/L) resistance. With the notable exceptions of I47A and I50L, most PI-SDRMs decreased in prevalence. Three candidate PI-SDRMs were accessory darunavir-resistance mutations (L10F, T74P, L89V). Adding the candidate SDRMs listed above was estimated to increase NRTI, NNRTI, and PI TDR prevalence by 0.1%, 0.3%, and 0.3%, respectively. We describe trends in the prevalence of nonpolymorphic HIV-1 DRMs in ART-experienced persons. These data should be considered in decisions regarding SDRM list updates and TDR monitoring. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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8 pages, 692 KiB  
Article
Increasing Capacity to Detect Clusters of Rapid HIV Transmission in Varied Populations—United States
by Alexandra M. Oster, Nivedha Panneer, Sheryl B. Lyss, R. Paul McClung, Meg Watson, Neeraja Saduvala, M. Cheryl Bañez Ocfemia, Laurie Linley, William M. Switzer, Joel O. Wertheim, Ellsworth Campbell, Angela L. Hernandez and Anne Marie France
Viruses 2021, 13(4), 577; https://doi.org/10.3390/v13040577 - 30 Mar 2021
Cited by 18 | Viewed by 2954
Abstract
Molecular cluster detection analyzes HIV sequences to identify rapid HIV transmission and inform public health responses. We describe changes in the capability to detect molecular clusters and in geographic variation in transmission dynamics. We examined the reporting completeness of HIV-1 polymerase sequences in [...] Read more.
Molecular cluster detection analyzes HIV sequences to identify rapid HIV transmission and inform public health responses. We describe changes in the capability to detect molecular clusters and in geographic variation in transmission dynamics. We examined the reporting completeness of HIV-1 polymerase sequences in quarterly National HIV Surveillance System datasets from December 2015 to December 2019. Priority clusters were identified quarterly. To understand populations recently affected by rapid transmission, we described the transmission risk and race/ethnicity of people in clusters first detected in 2018–2019. During December 2015 to December 2019, national sequence completeness increased from 26% to 45%. Of the 1212 people in the 136 clusters first detected in 2018–2019, 69% were men who have sex with men (MSM) and 11% were people who inject drugs (PWID). State-by-state analysis showed substantial variation in transmission risk and racial/ethnic groups in clusters of rapid transmission. HIV sequence reporting has increased nationwide. Molecular cluster analysis identifies rapid transmission in varied populations and identifies emerging patterns of rapid transmission in specific population groups, such as PWID, who, in 2015–2016, comprised only 1% of people in such molecular clusters. These data can guide efforts to focus, tailor, and scale up prevention and care services for these populations. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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12 pages, 2560 KiB  
Article
Early-Transmitted Variants and Their Evolution in a HIV-1 Positive Couple: NGS and Phylogenetic Analyses
by Alessia Lai, Vania Giacomet, Annalisa Bergna, Gian Vincenzo Zuccotti, Gianguglielmo Zehender, Mario Clerici, Daria Trabattoni and Claudio Fenizia
Viruses 2021, 13(3), 513; https://doi.org/10.3390/v13030513 - 19 Mar 2021
Cited by 1 | Viewed by 2390
Abstract
We had access to both components of a couple who became infected with human immunodeficiency virus (HIV)-1 through sexual behavior during the early initial phase of infection and before initiation of therapy. We analyzed blood samples obtained at the time of diagnosis and [...] Read more.
We had access to both components of a couple who became infected with human immunodeficiency virus (HIV)-1 through sexual behavior during the early initial phase of infection and before initiation of therapy. We analyzed blood samples obtained at the time of diagnosis and after six months of combined antiretroviral therapy. Next-generation sequencing (NGS) and phylogenetic analyses were used to investigate the transmission and evolution of HIV-1 quasispecies. Phylogenetic analyses were conducted using Bayesian inference methods. Both partners were infected with an HIV-1 B subtype. No evidence of viral recombination was observed. The lowest intrapersonal genetic distances were observed at baseline, before initiation of therapy, and in particular in the V1V2 fragment (distances ranging from 0.102 to 0.148). One HIV-1 single variant was concluded to be dominant in all of the HIV-1 regions analyzed, although some minor variants could be observed. The same tree structure was observed both at baseline and after six months of therapy. These are the first extended phylogenetic analyses performed on both members of a therapy-naïve couple within a few weeks of infection, and in which the effect of antiretroviral therapy on viral evolution was analyzed. Understanding which HIV-1 variants are most likely to be transmitted would allow a better understanding of viral evolution, possibly playing a role in vaccine design and prevention strategies. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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13 pages, 1515 KiB  
Article
Molecular Transmission Dynamics of Primary HIV Infections in Lazio Region, Years 2013–2020
by Lavinia Fabeni, Gabriella Rozera, Giulia Berno, Emanuela Giombini, Caterina Gori, Nicoletta Orchi, Gabriella De Carli, Silvia Pittalis, Vincenzo Puro, Carmela Pinnetti, Annalisa Mondi, Marta Camici, Maria Maddalena Plazzi, Andrea Antinori, Maria Rosaria Capobianchi and Isabella Abbate
Viruses 2021, 13(2), 176; https://doi.org/10.3390/v13020176 - 25 Jan 2021
Cited by 4 | Viewed by 2313
Abstract
Molecular investigation of primary HIV infections (PHI) is crucial to describe current dynamics of HIV transmission. Aim of the study was to investigate HIV transmission clusters (TC) in PHI referred during the years 2013–2020 to the National Institute for Infectious Diseases in Rome [...] Read more.
Molecular investigation of primary HIV infections (PHI) is crucial to describe current dynamics of HIV transmission. Aim of the study was to investigate HIV transmission clusters (TC) in PHI referred during the years 2013–2020 to the National Institute for Infectious Diseases in Rome (INMI), that is the Lazio regional AIDS reference centre, and factors possibly associated with inclusion in TC. These were identified by phylogenetic analysis, based on population sequencing of pol; a more in depth analysis was performed on TC of B subtype, using ultra-deep sequencing (UDS) of env. Of 270 patients diagnosed with PHI during the study period, 229 were enrolled (median follow-up 168 (IQR 96–232) weeks). Median age: 39 (IQR 32–48) years; 94.8% males, 86.5% Italians, 83.4% MSM, 56.8% carrying HIV-1 subtype B. Of them, 92.6% started early treatment within a median of 4 (IQR 2–7) days after diagnosis; median time to sustained suppression was 20 (IQR 8–32) weeks. Twenty TC (median size 3, range 2–9 individuals), including 68 patients, were identified. A diagnosis prior to 2015 was the unique factor associated with inclusion in a TC. Added value of UDS was the identification of shared quasispecies components in transmission pairs within TC. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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18 pages, 4022 KiB  
Article
Molecular Epidemiological Analysis of the Origin and Transmission Dynamics of the HIV-1 CRF01_AE Sub-Epidemic in Bulgaria
by Ivailo Alexiev, Ellsworth M. Campbell, Sergey Knyazev, Yi Pan, Lyubomira Grigorova, Reneta Dimitrova, Aleksandra Partsuneva, Anna Gancheva, Asya Kostadinova, Carole Seguin-Devaux, Ivaylo Elenkov, Nina Yancheva and William M. Switzer
Viruses 2021, 13(1), 116; https://doi.org/10.3390/v13010116 - 16 Jan 2021
Cited by 9 | Viewed by 3322
Abstract
HIV-1 subtype CRF01_AE is the second most predominant strain in Bulgaria, yet little is known about the molecular epidemiology of its origin and transmissibility. We used a phylodynamics approach to better understand this sub-epidemic by analyzing 270 HIV-1 polymerase (pol) sequences [...] Read more.
HIV-1 subtype CRF01_AE is the second most predominant strain in Bulgaria, yet little is known about the molecular epidemiology of its origin and transmissibility. We used a phylodynamics approach to better understand this sub-epidemic by analyzing 270 HIV-1 polymerase (pol) sequences collected from persons diagnosed with HIV/AIDS between 1995 and 2019. Using network analyses at a 1.5% genetic distance threshold (d), we found a large 154-member outbreak cluster composed mostly of persons who inject drugs (PWID) that were predominantly men. At d = 0.5%, which was used to identify more recent transmission, the large cluster dissociated into three clusters of 18, 12, and 7 members, respectively, five dyads, and 107 singletons. Phylogenetic analysis of the Bulgarian sequences with publicly available global sequences showed that CRF01_AE likely originated from multiple Asian countries, with Vietnam as the likely source of the outbreak cluster between 1988 and 1990. Our findings indicate that CRF01_AE was introduced into Bulgaria multiple times since 1988, and infections then rapidly spread among PWID locally with bridging to other risk groups and countries. CRF01_AE continues to spread in Bulgaria as evidenced by the more recent large clusters identified at d = 0.5%, highlighting the importance of public health prevention efforts in the PWID communities. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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13 pages, 2808 KiB  
Article
Identification of a New HIV-1 BC Intersubtype Circulating Recombinant Form (CRF108_BC) in Spain
by Javier E. Cañada, Elena Delgado, Horacio Gil, Mónica Sánchez, Sonia Benito, Elena García-Bodas, Carmen Gómez-González, Andrés Canut-Blasco, Joseba Portu-Zapirain, Ester Sáez de Adana, Mireia De la Peña, Sofía Ibarra, Gustavo Cilla, José Antonio Iribarren, Ana Martínez-Sapiña and Michael M. Thomson
Viruses 2021, 13(1), 93; https://doi.org/10.3390/v13010093 - 12 Jan 2021
Cited by 5 | Viewed by 2656
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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17 pages, 955 KiB  
Article
The Molecular Epidemiology and Transmission Dynamics of HIV Type 1 in a General Population Cohort in Uganda
by Deogratius Ssemwanga, Nicholas Bbosa, Rebecca N. Nsubuga, Alfred Ssekagiri, Anne Kapaata, Maria Nannyonjo, Faridah Nassolo, Alex Karabarinde, Joseph Mugisha, Janet Seeley, Gonzalo Yebra, Andrew Leigh Brown and Pontiano Kaleebu
Viruses 2020, 12(11), 1283; https://doi.org/10.3390/v12111283 - 10 Nov 2020
Cited by 4 | Viewed by 2966
Abstract
The General Population Cohort (GPC) in south-western Uganda has a low HIV-1 incidence rate (<1%). However, new infections continue to emerge. In this research, 3796 HIV-1 pol sequences (GPC: n = 1418, non-GPC sites: n = 1223, Central Uganda: n = 1010 and [...] Read more.
The General Population Cohort (GPC) in south-western Uganda has a low HIV-1 incidence rate (<1%). However, new infections continue to emerge. In this research, 3796 HIV-1 pol sequences (GPC: n = 1418, non-GPC sites: n = 1223, Central Uganda: n = 1010 and Eastern Uganda: n = 145) generated between 2003–2015 were analysed using phylogenetic methods with demographic data to understand HIV-1 transmission in this cohort and inform the epidemic response. HIV-1 subtype A1 was the most prevalent strain in the GPC area (GPC and non-GPC sites) (39.8%), central (45.9%) and eastern (52.4%) Uganda. However, in the GPC alone, subtype D was the predominant subtype (39.1%). Of the 524 transmission clusters identified by Cluster Picker, all large clusters (≥5 individuals, n = 8) involved individuals from the GPC. In a multivariate analysis, clustering was strongly associated with being female (adjusted Odds Ratio, aOR = 1.28; 95% CI, 1.06–1.54), being >25 years (aOR = 1.52; 95% CI, 1.16–2.0) and being a resident in the GPC (aOR = 6.90; 95% CI, 5.22–9.21). Phylogeographic analysis showed significant viral dissemination (Bayes Factor test, BF > 3) from the GPC without significant viral introductions (BF < 3) into the GPC. The findings suggest localized HIV-1 transmission in the GPC. Intensifying geographically focused combination interventions in the GPC would contribute towards controlling HIV-1 infections. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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15 pages, 5210 KiB  
Article
Increasing Prevalence of HIV-1 Transmitted Drug Resistance in Portugal: Implications for First Line Treatment Recommendations
by Marta Pingarilho, Victor Pimentel, Isabel Diogo, Sandra Fernandes, Mafalda Miranda, Andrea Pineda-Pena, Pieter Libin, Kristof Theys, M. Rosário O. Martins, Anne-Mieke Vandamme, Ricardo Camacho, Perpétua Gomes, Ana Abecasis and on behalf of the Portuguese HIV-1 Resistance Study Group
Viruses 2020, 12(11), 1238; https://doi.org/10.3390/v12111238 - 30 Oct 2020
Cited by 11 | Viewed by 3285
Abstract
Introduction: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR). Objective: To study the trends of [...] Read more.
Introduction: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR). Objective: To study the trends of TDR and ADR in patients followed up in Portuguese hospitals between 2001 and 2017. Methods: In total, 11,911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutation according to the WHO surveillance list. Genotypic resistance to ARV was evaluated with Stanford HIVdb v7.0. Patterns of TDR, ADR and the prevalence of mutations over time were analyzed using logistic regression. Results and Discussion: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (p < 0.001). This was due to a significant increase in both resistance to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs), from 5.6% to 6.7% (p = 0.002) and 2.9% to 8.9% (p < 0.001), respectively. TDR was associated with infection with subtype B, and with lower viral load levels (p < 0.05). The prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (p < 0.001), caused by decreasing drug resistance to all antiretroviral (ARV) classes (p < 0.001). Conclusions: While ADR has been decreasing since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgently necessary to develop public health programs to monitor the levels and patterns of TDR in newly diagnosed patients. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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16 pages, 1712 KiB  
Article
A Nationwide Study about the Dispersal Patterns of the Predominant HIV-1 Subtypes A1 and B in Greece: Inference of the Molecular Transmission Clusters
by Evangelia Georgia Kostaki, Maria Gova, Georgios Adamis, Georgios Xylomenos, Maria Chini, Nikos Mangafas, Marios Lazanas, Simeon Metallidis, Olga Tsachouridou, Vasileios Papastamopoulos, Dimitrios Chatzidimitriou, Eleni Kakalou, Anastasia Antoniadou, Antonios Papadopoulos, Mina Psichogiou, Dimitrios Basoulis, Dimitrios Pilalas, Ifigeneia Papageorgiou, Dimitra Paraskeva, Georgios Chrysos, Vasileios Paparizos, Sofia Kourkounti, Helen Sambatakou, Vasileios Bolanos, Nikolaos V. Sipsas, Malvina Lada, Emmanouil Barbounakis, Evrikleia Kantzilaki, Periklis Panagopoulos, Vasilis Petrakis, Stelios Drimis, Charalambos Gogos, Angelos Hatzakis, Apostolos Beloukas, Lemonia Skoura and Dimitrios Paraskevisadd Show full author list remove Hide full author list
Viruses 2020, 12(10), 1183; https://doi.org/10.3390/v12101183 - 19 Oct 2020
Cited by 6 | Viewed by 2963
Abstract
Our aim was to investigate the dispersal patterns and parameters associated with local molecular transmission clusters (MTCs) of subtypes A1 and B in Greece (predominant HIV-1 subtypes). The analysis focused on 1751 (28.4%) and 2575 (41.8%) sequences of subtype A1 and B, respectively. [...] Read more.
Our aim was to investigate the dispersal patterns and parameters associated with local molecular transmission clusters (MTCs) of subtypes A1 and B in Greece (predominant HIV-1 subtypes). The analysis focused on 1751 (28.4%) and 2575 (41.8%) sequences of subtype A1 and B, respectively. Identification of MTCs was based on phylogenetic analysis. The analyses identified 38 MTCs including 2–1518 subtype A1 sequences and 168 MTCs in the range of 2–218 subtype B sequences. The proportion of sequences within MTCs was 93.8% (1642/1751) and 77.0% (1982/2575) for subtype A1 and B, respectively. Transmissions within MTCs for subtype A1 were associated with risk group (Men having Sex with Men vs. heterosexuals, OR = 5.34, p < 0.001) and Greek origin (Greek vs. non-Greek origin, OR = 6.05, p < 0.001) and for subtype B, they were associated with Greek origin (Greek vs. non-Greek origin, OR = 1.57, p = 0.019), younger age (OR = 0.96, p < 0.001), and more recent sampling (time period: 2011–2015 vs. 1999–2005, OR = 3.83, p < 0.001). Our findings about the patterns of across and within country dispersal as well as the parameters associated with transmission within MTCs provide a framework for the application of the study of molecular clusters for HIV prevention. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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14 pages, 3091 KiB  
Article
Employing Molecular Phylodynamic Methods to Identify and Forecast HIV Transmission Clusters in Public Health Settings: A Qualitative Study
by Shannan N. Rich, Veronica L. Richards, Carla N. Mavian, William M. Switzer, Brittany Rife Magalis, Karalee Poschman, Shana Geary, Steven E. Broadway, Spencer B. Bennett, Jason Blanton, Thomas Leitner, J. Lucas Boatwright, Nichole E. Stetten, Robert L. Cook, Emma C. Spencer, Marco Salemi and Mattia Prosperi
Viruses 2020, 12(9), 921; https://doi.org/10.3390/v12090921 - 22 Aug 2020
Cited by 10 | Viewed by 3700
Abstract
Molecular HIV surveillance is a promising public health strategy for curbing the HIV epidemic. Clustering technologies used by health departments to date are limited in their ability to infer/forecast cluster growth trajectories. Resolution of the spatiotemporal dynamics of clusters, through phylodynamic and phylogeographic [...] Read more.
Molecular HIV surveillance is a promising public health strategy for curbing the HIV epidemic. Clustering technologies used by health departments to date are limited in their ability to infer/forecast cluster growth trajectories. Resolution of the spatiotemporal dynamics of clusters, through phylodynamic and phylogeographic modelling, is one potential strategy to develop a forecasting tool; however, the projected utility of this approach needs assessment. Prior to incorporating novel phylodynamic-based molecular surveillance tools, we sought to identify possible issues related to their feasibility, acceptability, interpretation, and utility. Qualitative data were collected via focus groups among field experts (n = 17, 52.9% female) using semi-structured, open-ended questions. Data were coded using an iterative process, first through the development of provisional themes and subthemes, followed by independent line-by-line coding by two coders. Most participants routinely used molecular methods for HIV surveillance. All agreed that linking molecular sequences to epidemiological data is important for improving HIV surveillance. We found that, in addition to methodological challenges, a variety of implementation barriers are expected in relation to the uptake of phylodynamic methods for HIV surveillance. The participants identified several opportunities to enhance current methods, as well as increase the usability and utility of promising works-in-progress. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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18 pages, 593 KiB  
Article
Evaluation of HIV Transmission Clusters among Natives and Foreigners Living in Italy
by Lavinia Fabeni, Maria Mercedes Santoro, Patrizia Lorenzini, Stefano Rusconi, Nicola Gianotti, Andrea Costantini, Loredana Sarmati, Andrea Antinori, Francesca Ceccherini-Silberstein, Antonella d’Arminio Monforte, Annalisa Saracino, Enrico Girardi and on behalf of the Icona Foundation Study Cohort
Viruses 2020, 12(8), 791; https://doi.org/10.3390/v12080791 - 23 Jul 2020
Cited by 9 | Viewed by 3192
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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15 pages, 2345 KiB  
Perspective
What Should Health Departments Do with HIV Sequence Data?
by Ethan Romero-Severson, Arshan Nasir and Thomas Leitner
Viruses 2020, 12(9), 1018; https://doi.org/10.3390/v12091018 - 12 Sep 2020
Cited by 9 | Viewed by 2678
Abstract
Many countries and US states have mandatory statues that require reporting of HIV clinical data including genetic sequencing results to the public health departments. Because genetic sequencing is a part of routine care for HIV infected persons, health departments have extensive sequence collections [...] Read more.
Many countries and US states have mandatory statues that require reporting of HIV clinical data including genetic sequencing results to the public health departments. Because genetic sequencing is a part of routine care for HIV infected persons, health departments have extensive sequence collections spanning years and even decades of the HIV epidemic. How should these data be used (or not) in public health practice? This is a complex, multi-faceted question that weighs personal risks against public health benefit. The answer is neither straightforward nor universal. However, to make that judgement—of how genetic sequence data should be used in describing and combating the HIV epidemic—we need a clear image of what a phylogenetically enhanced HIV surveillance system can do and what benefit it might provide. In this paper, we present a positive case for how up-to-date analysis of HIV sequence databases managed by health departments can provide unique and actionable information of how HIV is spreading in local communities. We discuss this question broadly, with examples from the US, as it is globally relevant for all health authorities that collect HIV genetic data. Full article
(This article belongs to the Special Issue HIV Molecular Epidemiology for Prevention 2020)
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