Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis

ATHENA observational cohort

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. Methods and Findings: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. Conclusions: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.

Original languageEnglish
Article numbere1001898
JournalPLoS Medicine
Volume12
Issue number11
DOIs
Publication statusPublished - 1 Nov 2015

Cite this

@article{75be2690f7d14177880081eca66f3721,
title = "Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis",
abstract = "Background: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. Methods and Findings: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52{\%}) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59{\%}) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35{\%}) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. Conclusions: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",
author = "{ATHENA observational cohort} and Daniela Bezemer and Anne Cori and Oliver Ratmann and {van Sighem}, Ard and Hermanides, {Hillegonda S.} and Dutilh, {Bas E.} and Luuk Gras and {Rodrigues Faria}, Nuno and {van den Hengel}, Rob and Duits, {Ashley J.} and Peter Reiss and {de Wolf}, Frank and Christophe Fraser and Prins, {J. M.} and Kuijpers, {T. W.} and Scherpbier, {H. J.} and {van der Meer}, {J. T.M.} and Wit, {F. W.M.N.} and Godfried, {M. H.} and P. Reiss and {van der Poll}, T. and Nellen, {F. J.B.} and Geerlings, {S. E.} and {van Vugt}, M. and D. Pajkrt and Bos, {J. C.} and Wiersinga, {W. J.} and {van der Valk}, M. and A. Goorhuis and Hovius, {J. W.} and {van Eden}, J. and A. Henderiks and {van Hes}, {A. M.H.} and M. Mutschelknauss and Nobel, {H. E.} and Pijnappel, {F. J.J.} and Westerman, {A. M.} and S. Jurriaans and Back, {N. K.T.} and Zaaijer, {H. L.} and {de Boer}, {M. G.J.} and Savelkoul, {P. H.M.} and Bierman, {W. F.W.} and {van Agtmael}, {M. A.} and M. Bomers and {de Vocht}, J. and Pettersson, {A. M.} and Vandenbroucke-Grauls, {C. M.J.E.} and Ang, {C. W.} and A. Jansen",
year = "2015",
month = "11",
day = "1",
doi = "10.1371/journal.pmed.1001898",
language = "English",
volume = "12",
journal = "PLoS Medicine",
issn = "1549-1277",
publisher = "Public Library of Science",
number = "11",

}

Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands : A Combined Mathematical Model and Phylogenetic Analysis. / ATHENA observational cohort.

In: PLoS Medicine, Vol. 12, No. 11, e1001898, 01.11.2015.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands

T2 - A Combined Mathematical Model and Phylogenetic Analysis

AU - ATHENA observational cohort

AU - Bezemer, Daniela

AU - Cori, Anne

AU - Ratmann, Oliver

AU - van Sighem, Ard

AU - Hermanides, Hillegonda S.

AU - Dutilh, Bas E.

AU - Gras, Luuk

AU - Rodrigues Faria, Nuno

AU - van den Hengel, Rob

AU - Duits, Ashley J.

AU - Reiss, Peter

AU - de Wolf, Frank

AU - Fraser, Christophe

AU - Prins, J. M.

AU - Kuijpers, T. W.

AU - Scherpbier, H. J.

AU - van der Meer, J. T.M.

AU - Wit, F. W.M.N.

AU - Godfried, M. H.

AU - Reiss, P.

AU - van der Poll, T.

AU - Nellen, F. J.B.

AU - Geerlings, S. E.

AU - van Vugt, M.

AU - Pajkrt, D.

AU - Bos, J. C.

AU - Wiersinga, W. J.

AU - van der Valk, M.

AU - Goorhuis, A.

AU - Hovius, J. W.

AU - van Eden, J.

AU - Henderiks, A.

AU - van Hes, A. M.H.

AU - Mutschelknauss, M.

AU - Nobel, H. E.

AU - Pijnappel, F. J.J.

AU - Westerman, A. M.

AU - Jurriaans, S.

AU - Back, N. K.T.

AU - Zaaijer, H. L.

AU - de Boer, M. G.J.

AU - Savelkoul, P. H.M.

AU - Bierman, W. F.W.

AU - van Agtmael, M. A.

AU - Bomers, M.

AU - de Vocht, J.

AU - Pettersson, A. M.

AU - Vandenbroucke-Grauls, C. M.J.E.

AU - Ang, C. W.

AU - Jansen, A.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Background: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. Methods and Findings: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. Conclusions: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.

AB - Background: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. Methods and Findings: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. Conclusions: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.

UR - http://www.scopus.com/inward/record.url?scp=85000349756&partnerID=8YFLogxK

U2 - 10.1371/journal.pmed.1001898

DO - 10.1371/journal.pmed.1001898

M3 - Article

VL - 12

JO - PLoS Medicine

JF - PLoS Medicine

SN - 1549-1277

IS - 11

M1 - e1001898

ER -