A highly virulent variant of HIV-1 circulating in the Netherlands

Netherlands ATHENA HIV Observational Cohort; BEEHIVE Collaboration; Netherlands ATHENA HIV Observational Cohort†

doi:https://doi.org/10.1126/science.abk1688

A highly virulent variant of HIV-1 circulating in the Netherlands

Netherlands ATHENA HIV Observational Cohort, BEEHIVE Collaboration, Netherlands ATHENA HIV Observational Cohort†

Research output: Contribution to journal › Article › Academic › peer-review

29 Citations (Scopus)

Abstract

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV - CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences - is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

Original language	English
Article number	A30
Pages (from-to)	540-545
Number of pages	6
Journal	Science
Volume	375
Issue number	6580
DOIs	https://doi.org/10.1126/science.abk1688
Publication status	Published - 4 Feb 2022

Keywords

Adult
Anti-HIV Agents/therapeutic use
CD4 Lymphocyte Count
Evolution, Molecular
Female
Genome, Viral
Genotype
HIV Infections/drug therapy
HIV-1/genetics
Humans
Male
Mutation
Netherlands
Phylogeny
Viral Load
Virulence

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https://doi.org/10.1126/science.abk1688

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@article{d4d6dfaedec949d39bae18a993f3d708,

title = "A highly virulent variant of HIV-1 circulating in the Netherlands",

abstract = "We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV - CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences - is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.",

keywords = "Adult, Anti-HIV Agents/therapeutic use, CD4 Lymphocyte Count, Evolution, Molecular, Female, Genome, Viral, Genotype, HIV Infections/drug therapy, HIV-1/genetics, Humans, Male, Mutation, Netherlands, Phylogeny, Viral Load, Virulence",

author = "Chris Wymant and Daniela Bezemer and Fran{\c c}ois Blanquart and Luca Ferretti and Astrid Gall and Matthew Hall and Tanya Golubchik and Margreet Bakker and Ong, {Swee Hoe} and Lele Zhao and David Bonsall and {de Cesare}, Mariateresa and George MacIntyre-Cockett and Lucie Abeler-D{\"o}rner and Jan Albert and Norbert Bannert and Jacques Fellay and Grabowski, {M. Kate} and Barbara Gunsenheimer-Bartmeyer and G{\"u}nthard, {Huldrych F.} and Pia Kivel{\"a} and Kouyos, {Roger D.} and Oliver Laeyendecker and Laurence Meyer and Kholoud Porter and Matti Ristola and {van Sighem}, Ard and Ben Berkhout and Paul Kellam and {Netherlands ATHENA HIV Observational Cohort} and Marion Cornelissen and {BEEHIVE Collaboration} and Peter Reiss and Christophe Fraser and {Netherlands ATHENA HIV Observational Cohort†} and {van der Valk}, M and Geerlings, {S E} and A Goorhuis and Hovius, {J W} and Nellen, {F J B} and {van der Poll}, T and Prins, {J M} and {van Vugt}, M and Wiersinga, {W J} and Zaaijer, {H L} and Schinkel, {C J} and Wolthers, {K C} and Peters, {E J G} and {van Agtmael}, {M A} and Autar, {R S} and M Bomers and Sigaloff, {K C E} and Laan, {L M} and Ang, {C W} and {van Houdt}, R and M Jonges and Kuijpers, {T W} and D Pajkrt and Scherpbier, {H J} and {de Boer}, C and {van den Berge}, M and B Wintermans and Brouwer, {A E} and {van Beek}, {J E A} and {de Groot}, J and Koopmans, {M P G} and {van Rossum}, {A M C} and E Visser and Schippers, {E F} and {de Boer}, {M G J} and {den Hollander}, {J G} and Brouwer, {A E} and Smit, {J V} and {van Vonderen}, {M G A} and W Kortmann and Jansen, {E R} and M Hoogewerf and W Rozemeijer and M Kok and {de Haan}, M and Stelma, {F F} and R Jansen and Verhagen, {D W M} and {van Wijk}, M and Bierman, {W F W} and A Boonstra and Arends, {J E} and {van Berkel}, M and {van Rooijen}, {C S A M} and Loeffen, {Y G T} and {van der Meer}, I and C Smit and {de Jong}, A and {de Groot}, L and M Bezemer and Visser, {K M} and Jean-Jacques Girard and G Singh",

note = "Funding Information: This study was funded by ERC Advanced Grant PBDR-339251 and a Li Ka Shing Foundation grant, both awarded to C.F. The ATHENA Cohort is managed by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment. Publisher Copyright: Copyright {\textcopyright} 2022 The Authors, some rights reserved.",

year = "2022",

month = feb,

day = "4",

doi = "https://doi.org/10.1126/science.abk1688",

language = "English",

volume = "375",

pages = "540--545",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6580",

}

TY - JOUR

T1 - A highly virulent variant of HIV-1 circulating in the Netherlands

AU - Wymant, Chris

AU - Bezemer, Daniela

AU - Blanquart, François

AU - Ferretti, Luca

AU - Gall, Astrid

AU - Hall, Matthew

AU - Golubchik, Tanya

AU - Bakker, Margreet

AU - Ong, Swee Hoe

AU - Zhao, Lele

AU - Bonsall, David

AU - de Cesare, Mariateresa

AU - MacIntyre-Cockett, George

AU - Abeler-Dörner, Lucie

AU - Albert, Jan

AU - Bannert, Norbert

AU - Fellay, Jacques

AU - Grabowski, M. Kate

AU - Gunsenheimer-Bartmeyer, Barbara

AU - Günthard, Huldrych F.

AU - Kivelä, Pia

AU - Kouyos, Roger D.

AU - Laeyendecker, Oliver

AU - Meyer, Laurence

AU - Porter, Kholoud

AU - Ristola, Matti

AU - van Sighem, Ard

AU - Berkhout, Ben

AU - Kellam, Paul

AU - Netherlands ATHENA HIV Observational Cohort

AU - Cornelissen, Marion

AU - BEEHIVE Collaboration

AU - Reiss, Peter

AU - Fraser, Christophe

AU - Netherlands ATHENA HIV Observational Cohort†

AU - van der Valk, M

AU - Geerlings, S E

AU - Goorhuis, A

AU - Hovius, J W

AU - Nellen, F J B

AU - van der Poll, T

AU - Prins, J M

AU - van Vugt, M

AU - Wiersinga, W J

AU - Zaaijer, H L

AU - Schinkel, C J

AU - Wolthers, K C

AU - Peters, E J G

AU - van Agtmael, M A

AU - Autar, R S

AU - Bomers, M

AU - Sigaloff, K C E

AU - Laan, L M

AU - Ang, C W

AU - van Houdt, R

AU - Jonges, M

AU - Kuijpers, T W

AU - Pajkrt, D

AU - Scherpbier, H J

AU - de Boer, C

AU - van den Berge, M

AU - Wintermans, B

AU - Brouwer, A E

AU - van Beek, J E A

AU - de Groot, J

AU - Koopmans, M P G

AU - van Rossum, A M C

AU - Visser, E

AU - Schippers, E F

AU - de Boer, M G J

AU - den Hollander, J G

AU - Brouwer, A E

AU - Smit, J V

AU - van Vonderen, M G A

AU - Kortmann, W

AU - Jansen, E R

AU - Hoogewerf, M

AU - Rozemeijer, W

AU - Kok, M

AU - de Haan, M

AU - Stelma, F F

AU - Jansen, R

AU - Verhagen, D W M

AU - van Wijk, M

AU - Bierman, W F W

AU - Boonstra, A

AU - Arends, J E

AU - van Berkel, M

AU - van Rooijen, C S A M

AU - Loeffen, Y G T

AU - van der Meer, I

AU - Smit, C

AU - de Jong, A

AU - de Groot, L

AU - Bezemer, M

AU - Visser, K M

AU - Girard, Jean-Jacques

AU - Singh, G

N1 - Funding Information: This study was funded by ERC Advanced Grant PBDR-339251 and a Li Ka Shing Foundation grant, both awarded to C.F. The ATHENA Cohort is managed by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment. Publisher Copyright: Copyright © 2022 The Authors, some rights reserved.

PY - 2022/2/4

Y1 - 2022/2/4

N2 - We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV - CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences - is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

AB - We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV - CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences - is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

KW - Adult

KW - Anti-HIV Agents/therapeutic use

KW - CD4 Lymphocyte Count

KW - Evolution, Molecular

KW - Female

KW - Genome, Viral

KW - Genotype

KW - HIV Infections/drug therapy

KW - HIV-1/genetics

KW - Humans

KW - Male

KW - Mutation

KW - Netherlands

KW - Phylogeny

KW - Viral Load

KW - Virulence

UR - http://www.scopus.com/inward/record.url?scp=85124019619&partnerID=8YFLogxK

U2 - https://doi.org/10.1126/science.abk1688

DO - https://doi.org/10.1126/science.abk1688

M3 - Article

C2 - 35113714

SN - 0036-8075

VL - 375

SP - 540

EP - 545

JO - Science

JF - Science

IS - 6580

M1 - A30

ER -

A highly virulent variant of HIV-1 circulating in the Netherlands

Abstract

Keywords

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