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BMC Med. 2019 Jan 8;17(1):4. doi: 10.1186/s12916-018-1241-1.

HIV-1 molecular transmission clusters in nine European countries and Canada: association with demographic and clinical factors.

Author information

1
Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 115 27, Athens, Greece. dparask@med.uoa.gr.
2
Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 115 27, Athens, Greece. beloukas@liverpool.ac.uk.
3
Institute of Infection and Global Health, University of Liverpool, Ronald Ross Building, 8 West Derby Street, Liverpool, L69 7BE, UK. beloukas@liverpool.ac.uk.
4
Department of Biomedical Sciences, School of Health Sciences, University of West Attica, Agiou Spiridonos Str (Campus 1), 12243, Athens, Greece. beloukas@liverpool.ac.uk.
5
Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 115 27, Athens, Greece.
6
Department of Internal Medicine, Puerta de Hierro Research Institute and University Hospital, Alle Manuel de Falla, 1, 28222, Madrid, Majadahonda, Spain.
7
Robert Koch Institute, Nordufer 20, 13353, Berlin, Germany.
8
Inserm, CESP U1018, Univ Paris-Sud, Department of Epidemiology and Population Health, APHP, Hôpital Bicêtre, 78 Rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France.
9
Department of Dermatology and Venerology, Innsbruck Medical University, Anichstraße 35, 6020, Innsbruck, Austria.
10
Department of Microbiology, Immunology and Infectious Diseases (MIID), University of Calgary, 269 Heritage Medical Research Building, 24 Ave NW, Calgary, Alberta, Canada.
11
Academic Medical Center, University of Amsterdam, Netherlands and Department of Infectious Diseases, Amsterdam Infection and Immunity Institute, Spui 21, 1012 WX, Amsterdam, Netherlands.
12
Department of Health Sciences, University of Milan, Via di Rudinì, 8, 20142, Milan, Italy.
13
Department of Microbiology, Oslo University Hospital, OUS HF Rikshospitalet, Postboks 4950 Nydalen, 0424, Oslo, Norway.
14
Institute of Clinical Medicine, University of Oslo, Sognsvannsveien 20, Rikshospitalet, 0372, Oslo, Norway.
15
University College London Institute for Global Health, Institute of Child Health, 3rd floor, 30 Guilford Street, London, WC1N 1EH, UK.

Abstract

BACKGROUND:

Knowledge of HIV-1 molecular transmission clusters (MTCs) is important, especially in large-scale datasets, for designing prevention programmes and public health intervention strategies. We used a large-scale HIV-1 sequence dataset from nine European HIV cohorts and one Canadian, to identify MTCs and investigate factors associated with the probability of belonging to MTCs.

METHODS:

To identify MTCs, we applied maximum likelihood inferences on partial pol sequences from 8955 HIV-positive individuals linked to demographic and clinical data. MTCs were defined using two different criteria: clusters with bootstrap support >75% (phylogenetic confidence criterion) and clusters consisting of sequences from a specific region at a proportion of >75% (geographic criterion) compared to the total number of sequences within the network. Multivariable logistic regression analysis was used to assess factors associated with MTC clustering.

RESULTS:

Although 3700 (41%) sequences belonged to MTCs, proportions differed substantially by country and subtype, ranging from 7% among UK subtype C sequences to 63% among German subtype B sequences. The probability of belonging to an MTC was independently less likely for women than men (OR = 0.66; P < 0.001), older individuals (OR = 0.79 per 10-year increase in age; P < 0.001) and people of non-white ethnicity (OR = 0.44; P < 0.001 and OR = 0.70; P = 0.002 for black and 'other' versus white, respectively). It was also more likely among men who have sex with men (MSM) than other risk groups (OR = 0.62; P < 0.001 and OR = 0.69; P = 0.002 for people who inject drugs, and sex between men and women, respectively), subtype B (ORs 0.36-0.70 for A, C, CRF01 and CRF02 versus B; all P < 0.05), having a well-estimated date of seroconversion (OR = 1.44; P < 0.001), a later calendar year of sampling (ORs 2.01-2.61 for all post-2002 periods versus pre-2002; all P < 0.01), and being naïve to antiretroviral therapy at sampling (OR = 1.19; P = 0.010).

CONCLUSIONS:

A high proportion (>40%) of individuals belonged to MTCs. Notably, the HIV epidemic dispersal appears to be driven by subtype B viruses spread within MSM networks. Expansion of regional epidemics seems mainly associated with recent MTCs, rather than the growth of older, established ones. This information is important for designing prevention and public health intervention strategies.

KEYWORDS:

Clusters; HIV; HIV epidemic; Molecular epidemiology; Phylogenies; Regional epidemics; Transmission networks

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