CD4 T cell decline following HIV seroconversion in individuals with and without CXCR4-tropic virus

on behalf of the CASCADE Collaboration in EuroCoord

doi:10.1093/jac/dkx247

CD4 T cell decline following HIV seroconversion in individuals with and without CXCR4-tropic virus

on behalf of the CASCADE Collaboration in EuroCoord

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

7 Citations (Scopus)

Abstract

Background: THe natural clinical and immunological courses following HIV seroconversion with CXCR4-tropic or dual-mixed (X4/DM) viruses are controversial. We compared spontaneous immunological outcome in patients harbouring an X4/DM virus at the time of seroconversion with those harbouring a CCR5-tropic (R5) virus. Methods: Data were included from patients participating in CASCADE, a large cohort collaboration of HIV seroconverters, with ≥ 2 years of follow-up since seroconversion. The HIV envelope gene was sequenced from frozen plasma samples collected at enrolment, and HIV tropismwas determined using Geno 2Pheno (false-positive rate 10%). The spontaneous CD4 T cell evolution was compared by modelling CD4 kinetics using linear mixed-effects models with random intercept and random slope. Results: A total of 1387 patients were eligible. Median time between seroconversion and enrolment was 1month (range 0-3). At enrolment, 202 of 1387 (15%) harboured an X4/DM-tropic virus. CD4 decrease slopes were not significantly different according to HIV-1 tropism during the first 30months after seroconversion. No marked change in these results was found after adjusting for age, year of seroconversion and baseline HIV viral load. Time to antiretroviral treatment initiation was not statistically different between patients harbouring an R5 (20.76months) and those harbouring an X4/DM-tropic virus (22.86months, logrank test P"0.32). Conclusions: In this large cohort collaboration, 15% of the patients harboured an X4/DM virus close to HIV seroconversion. Patients harbouring X4/DM-tropic viruses close to seroconversion did not have an increased risk of disease progression, estimated by the decline in CD4 T cell count or time to combined ART initiation.

Original language	English
Pages (from-to)	2862-2868
Number of pages	7
Journal	Journal of Antimicrobial Chemotherapy
Volume	72
Issue number	10
DOIs	https://doi.org/10.1093/jac/dkx247
Publication status	Published - 1 Oct 2017

Bibliographical note

Funding Information:
This study was funded by the CASCADE collaboration in EuroCOORD. CASCADE Steering Committee Julia Del Amo (Chair), Laurence Meyer (Vice Chair), Heiner C. Bucher, Geneviève Chêne, Osamah Hamouda, Deenan Pillay, Maria Prins, Magda Rosinska, Caroline Sabin and Giota Touloumi. CASCADE Co-Ordinating Centre Kholoud Porter (Project Leader), Ashley Olson, Andrea Cartier, Lorraine Fradette, Sarah Walker and Abdel Babiker. CASCADE Clinical Advisory Board Heiner C. Bucher, Andrea De Luca, Martin Fisher, Roberto Muga. CASCADE Collaborators Australia PHAEDRA cohort (Tony Kelleher, David Cooper, Pat Grey, Robert Finlayson, Mark Bloch) Sydney AIDS Prospective Study and Sydney Primary HIV Infection cohort (Tony Kelleher, Tim Ramacciotti, Linda Gelgor, David Cooper, Don Smith); Austria Austrian HIV Cohort Study (Robert Zangerle); Canada South Alberta clinic (John Gill); Estonia Tartu Ülikool (Irja Lutsar); France ANRS CO3 Aquitaine cohort (Geneviève Chêne, Francois Dabis, Rodolphe Thiebaut), ANRS CO4 French Hospital Database (Dominique Costagliola, Marguerite Guiguet), Lyon Primary Infection cohort (Philippe Vanhems), French ANRS CO6 PRIMO cohort (Marie-Laure Chaix, Jade Ghosn), ANRS CO2 SEROCO cohort (Laurence Meyer, Faroudy Boufassa); Germany German HIV-1 seroconverter cohort (Osamah Hamouda, Karolin Meixenberger, Norbert Bannert, Barbara Bartmeyer); Greece AMACS (Anastasia Antoniadou, Georgios Chrysos, Georgios L. Daikos); Greek Haemophilia cohort (Giota Touloumi, Nikos Pantazis, Olga Katsarou); Italy Italian Seroconversion Study (Giovanni Rezza, Maria Dorrucci), ICONA cohort (Antonella d'Arminio Monforte, Andrea De Luca); Netherlands Amsterdam Cohort Studies among homosexual men and drug users (Maria Prins, Ronald Geskus, Jannie van der Helm, Hanneke Schuitemaker); Norway Oslo and Ulleval Hospital cohorts (Mette Sannes, Oddbjorn Brubakk, Anne-Marte Bakken Kran); Poland National Institute of Hygiene (Magdalena Rosinska); Spain Badalona IDU hospital cohort (Roberto Muga, Jordi Tor), Barcelona IDU Cohort (Patricia Garcia de Olalla, Joan Cayla), CoRIS-scv (Julia del Amo, Santiago Moreno, Susana Monge); Madrid cohort (Julia Del Amo, Jorge del Romero), Valencia IDU cohort (Santiago Pérez-Hoyos); Sweden Swedish InfCare HIV Cohort, Sweden (Anders Sönnerborg); Switzerland Swiss HIV Cohort Study (Heiner C. Bucher, Huldrych Günthard, Alexandra Scherrer); Ukraine Perinatal Prevention of AIDS Initiative (Ruslan Malyuta); United Kingdom Public Health England (Gary Murphy), UK Register of HIV Seroconverters (Kholoud Porter, Anne Johnson, Andrew Phillips, Abdel Babiker), University College London (Deenan Pillay); African cohorts: Genital Shedding Study (US: Charles Morrison; Family Health International, Robert Salata, Case Western Reserve University, Uganda: Roy Mugerwa, Makerere University, Zimbabwe: Tsungai Chipato, University of Zimbabwe); International AIDS Vaccine Initiative (IAVI) Early Infections Cohort (Kenya, Rwanda, South Africa, Uganda, Zambia: Matt A. Price, IAVI, USA; Jill Gilmour, IAVI, UK; Anatoli Kamali, IAVI, Kenya; Etienne Karita, Projet San Francisco, Rwanda). EuroCoord Executive Board Fiona Burns, University College London, UK; Geneviève Ch^ene, University of Bordeaux, France; Dominique Costagliola (Scientific Coordinator), Institut National de la Santé et de la Recherche Médicale, France; Carlo Giaquinto, Fondazione PENTA, Italy; Jesper Grarup, Region Hovedstaden, Denmark; Ole Kirk, Region Hovedstaden, Denmark; Laurence Meyer, Institut National de la Santé et de la Recherche Médicale, France; Heather Bailey, University College London, UK; Alain Volny Anne, European AIDS Treatment Group, France; Alex Panteleev, St Petersburg City AIDS Centre, Russian Federation; Andrew Phillips, University College London, UK, Kholoud Porter, University College London, UK; Claire Thorne, University College London, UK. EuroCoord Council of Partners Jean-Pierre Aboulker, Institut National de la Santé et de la Recherche Médicale, France; Jan Albert, Karolinska Institute, Sweden; Silvia Asandi, Romanian Angel Appeal Foundation, Romania; Geneviève Chêne, University of Bordeaux, France; Dominique Costagliola (chair), INSERM, France; Antonella d'Arminio Monforte, ICoNA Foundation, Italy; Stéphane De Wit, St Pierre University Hospital, Belgium; Peter Reiss, Stichting HIV Monitoring, Netherlands; Julia Del Amo, Instituto de Salud Carlos III, Spain; José Gatell, Fundació Privada Clínic per a la Recerca Bíomèdica, Spain; Carlo Giaquinto, Fondazione PENTA, Italy; Osamah Hamouda, Robert Koch Institut, Germany; Igor Karpov, University of Minsk, Belarus; Bruno Ledergerber, University of Zurich, Switzerland; Jens Lundgren, Region Hovedstaden, Denmark; Ruslan Malyuta, Perinatal Prevention of AIDS Initiative, Ukraine; Claus Møller, Cadpeople A/S, Denmark; Kholoud Porter, University College London, United Kingdom; Maria Prins, Academic Medical Centre, Netherlands; Aza Rakhmanova, St Petersburg City AIDS Centre, Russian Federation; Jürgen Rockstroh, University of Bonn, Germany; Magda Rosinska, National Institute of Public Health, National Institute of Hygiene, Poland; Manjinder Sandhu, Genome Research Limited; Claire Thorne, University College London, UK; Giota Touloumi, National and Kapodistrian University of Athens, Greece; Alain Volny Anne, European AIDS Treatment Group, France. EuroCoord External Advisory Board David Cooper, University of New South Wales, Australia; Nikos Dedes, Positive Voice, Greece; Kevin Fenton, Public Health England, USA; David Pizzuti, Gilead Sciences, USA; Marco Vitoria, WHO, Switzerland. EuroCoord Secretariat Silvia Faggion, Fondazione PENTA, Italy; Lorraine Fradette, University College London, UK; Richard Frost, University College London, UK; Andrea Cartier, University College London, UK; Dorthe Raben, Region Hovedstaden, Denmark; Christine Schwimmer, University of Bordeaux, France; Martin Scott, UCL European Research & Innovation Office, UK.

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10.1093/jac/dkx247

Cite this

@article{b62697d265424c3db0308889f4372616,

title = "CD4 T cell decline following HIV seroconversion in individuals with and without CXCR4-tropic virus",

abstract = "Background: THe natural clinical and immunological courses following HIV seroconversion with CXCR4-tropic or dual-mixed (X4/DM) viruses are controversial. We compared spontaneous immunological outcome in patients harbouring an X4/DM virus at the time of seroconversion with those harbouring a CCR5-tropic (R5) virus. Methods: Data were included from patients participating in CASCADE, a large cohort collaboration of HIV seroconverters, with ≥ 2 years of follow-up since seroconversion. The HIV envelope gene was sequenced from frozen plasma samples collected at enrolment, and HIV tropismwas determined using Geno 2Pheno (false-positive rate 10\%). The spontaneous CD4 T cell evolution was compared by modelling CD4 kinetics using linear mixed-effects models with random intercept and random slope. Results: A total of 1387 patients were eligible. Median time between seroconversion and enrolment was 1month (range 0-3). At enrolment, 202 of 1387 (15\%) harboured an X4/DM-tropic virus. CD4 decrease slopes were not significantly different according to HIV-1 tropism during the first 30months after seroconversion. No marked change in these results was found after adjusting for age, year of seroconversion and baseline HIV viral load. Time to antiretroviral treatment initiation was not statistically different between patients harbouring an R5 (20.76months) and those harbouring an X4/DM-tropic virus (22.86months, logrank test P{"}0.32). Conclusions: In this large cohort collaboration, 15\% of the patients harboured an X4/DM virus close to HIV seroconversion. Patients harbouring X4/DM-tropic viruses close to seroconversion did not have an increased risk of disease progression, estimated by the decline in CD4 T cell count or time to combined ART initiation.",

author = "\{on behalf of the CASCADE Collaboration in EuroCoord\} and Jade Ghosn and Tatiana Bayan and Karolin Meixenberger and Laurent Tran and Pierre Frange and Monforte, \{Antonella d.Arminio\} and Robert Zangerle and \{de Mendoza\}, Carmen and Evguenia Krastinova and Kholoud Porter and Laurence Meyer and Chaix, \{Marie Laure\} and Fiona Burns and Genevi{\`e}ve Chene and Dominique Costagliola and Carlo Giaquinto and Jesper Grarup and Ole Kirk and Laurence Meyer and Heather Bailey and Anne, \{Alain Volny\} and Alex Panteleev and Andrew Phillips and Claire Thorne and Aboulker, \{Jean Pierre\} and Jan Albert and Silvia Asandi and Genevi{\`e}ve Cene and Dominique Costagliola and Monforte, \{Antonella d.Arminio\} and \{De Wit\}, St{\'e}phane and Peter Reiss and \{Del Amo\}, Julia and Jos{\'e} Gatell and Carlo Giaquinto and Osamah Hamouda and Igor Karpov and Bruno Ledergerber and Jens Lundgren and Ruslan Malyuta and Claus M{\o}ller and Maria Prins and Aza Rakhmanova and J{\"u}rgen Rockstroh and Magda Rosinska and Manjinder Sandhu and Claire Thorne and Giota Touloumi and Anne, \{Alain Volny\} and Kevin Fenton",

note = "Funding Information: This study was funded by the CASCADE collaboration in EuroCOORD. CASCADE Steering Committee Julia Del Amo (Chair), Laurence Meyer (Vice Chair), Heiner C. Bucher, Genevi{\`e}ve Ch{\^e}ne, Osamah Hamouda, Deenan Pillay, Maria Prins, Magda Rosinska, Caroline Sabin and Giota Touloumi. CASCADE Co-Ordinating Centre Kholoud Porter (Project Leader), Ashley Olson, Andrea Cartier, Lorraine Fradette, Sarah Walker and Abdel Babiker. CASCADE Clinical Advisory Board Heiner C. Bucher, Andrea De Luca, Martin Fisher, Roberto Muga. CASCADE Collaborators Australia PHAEDRA cohort (Tony Kelleher, David Cooper, Pat Grey, Robert Finlayson, Mark Bloch) Sydney AIDS Prospective Study and Sydney Primary HIV Infection cohort (Tony Kelleher, Tim Ramacciotti, Linda Gelgor, David Cooper, Don Smith); Austria Austrian HIV Cohort Study (Robert Zangerle); Canada South Alberta clinic (John Gill); Estonia Tartu {\"U}likool (Irja Lutsar); France ANRS CO3 Aquitaine cohort (Genevi{\`e}ve Ch{\^e}ne, Francois Dabis, Rodolphe Thiebaut), ANRS CO4 French Hospital Database (Dominique Costagliola, Marguerite Guiguet), Lyon Primary Infection cohort (Philippe Vanhems), French ANRS CO6 PRIMO cohort (Marie-Laure Chaix, Jade Ghosn), ANRS CO2 SEROCO cohort (Laurence Meyer, Faroudy Boufassa); Germany German HIV-1 seroconverter cohort (Osamah Hamouda, Karolin Meixenberger, Norbert Bannert, Barbara Bartmeyer); Greece AMACS (Anastasia Antoniadou, Georgios Chrysos, Georgios L. Daikos); Greek Haemophilia cohort (Giota Touloumi, Nikos Pantazis, Olga Katsarou); Italy Italian Seroconversion Study (Giovanni Rezza, Maria Dorrucci), ICONA cohort (Antonella d'Arminio Monforte, Andrea De Luca); Netherlands Amsterdam Cohort Studies among homosexual men and drug users (Maria Prins, Ronald Geskus, Jannie van der Helm, Hanneke Schuitemaker); Norway Oslo and Ulleval Hospital cohorts (Mette Sannes, Oddbjorn Brubakk, Anne-Marte Bakken Kran); Poland National Institute of Hygiene (Magdalena Rosinska); Spain Badalona IDU hospital cohort (Roberto Muga, Jordi Tor), Barcelona IDU Cohort (Patricia Garcia de Olalla, Joan Cayla), CoRIS-scv (Julia del Amo, Santiago Moreno, Susana Monge); Madrid cohort (Julia Del Amo, Jorge del Romero), Valencia IDU cohort (Santiago P{\'e}rez-Hoyos); Sweden Swedish InfCare HIV Cohort, Sweden (Anders S{\"o}nnerborg); Switzerland Swiss HIV Cohort Study (Heiner C. Bucher, Huldrych G{\"u}nthard, Alexandra Scherrer); Ukraine Perinatal Prevention of AIDS Initiative (Ruslan Malyuta); United Kingdom Public Health England (Gary Murphy), UK Register of HIV Seroconverters (Kholoud Porter, Anne Johnson, Andrew Phillips, Abdel Babiker), University College London (Deenan Pillay); African cohorts: Genital Shedding Study (US: Charles Morrison; Family Health International, Robert Salata, Case Western Reserve University, Uganda: Roy Mugerwa, Makerere University, Zimbabwe: Tsungai Chipato, University of Zimbabwe); International AIDS Vaccine Initiative (IAVI) Early Infections Cohort (Kenya, Rwanda, South Africa, Uganda, Zambia: Matt A. Price, IAVI, USA; Jill Gilmour, IAVI, UK; Anatoli Kamali, IAVI, Kenya; Etienne Karita, Projet San Francisco, Rwanda). EuroCoord Executive Board Fiona Burns, University College London, UK; Genevi{\`e}ve Ch\textasciicircum{}ene, University of Bordeaux, France; Dominique Costagliola (Scientific Coordinator), Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale, France; Carlo Giaquinto, Fondazione PENTA, Italy; Jesper Grarup, Region Hovedstaden, Denmark; Ole Kirk, Region Hovedstaden, Denmark; Laurence Meyer, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale, France; Heather Bailey, University College London, UK; Alain Volny Anne, European AIDS Treatment Group, France; Alex Panteleev, St Petersburg City AIDS Centre, Russian Federation; Andrew Phillips, University College London, UK, Kholoud Porter, University College London, UK; Claire Thorne, University College London, UK. EuroCoord Council of Partners Jean-Pierre Aboulker, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale, France; Jan Albert, Karolinska Institute, Sweden; Silvia Asandi, Romanian Angel Appeal Foundation, Romania; Genevi{\`e}ve Ch{\^e}ne, University of Bordeaux, France; Dominique Costagliola (chair), INSERM, France; Antonella d'Arminio Monforte, ICoNA Foundation, Italy; St{\'e}phane De Wit, St Pierre University Hospital, Belgium; Peter Reiss, Stichting HIV Monitoring, Netherlands; Julia Del Amo, Instituto de Salud Carlos III, Spain; Jos{\'e} Gatell, Fundaci{\'o} Privada Cl{\'i}nic per a la Recerca B{\'i}om{\`e}dica, Spain; Carlo Giaquinto, Fondazione PENTA, Italy; Osamah Hamouda, Robert Koch Institut, Germany; Igor Karpov, University of Minsk, Belarus; Bruno Ledergerber, University of Zurich, Switzerland; Jens Lundgren, Region Hovedstaden, Denmark; Ruslan Malyuta, Perinatal Prevention of AIDS Initiative, Ukraine; Claus M{\o}ller, Cadpeople A/S, Denmark; Kholoud Porter, University College London, United Kingdom; Maria Prins, Academic Medical Centre, Netherlands; Aza Rakhmanova, St Petersburg City AIDS Centre, Russian Federation; J{\"u}rgen Rockstroh, University of Bonn, Germany; Magda Rosinska, National Institute of Public Health, National Institute of Hygiene, Poland; Manjinder Sandhu, Genome Research Limited; Claire Thorne, University College London, UK; Giota Touloumi, National and Kapodistrian University of Athens, Greece; Alain Volny Anne, European AIDS Treatment Group, France. EuroCoord External Advisory Board David Cooper, University of New South Wales, Australia; Nikos Dedes, Positive Voice, Greece; Kevin Fenton, Public Health England, USA; David Pizzuti, Gilead Sciences, USA; Marco Vitoria, WHO, Switzerland. EuroCoord Secretariat Silvia Faggion, Fondazione PENTA, Italy; Lorraine Fradette, University College London, UK; Richard Frost, University College London, UK; Andrea Cartier, University College London, UK; Dorthe Raben, Region Hovedstaden, Denmark; Christine Schwimmer, University of Bordeaux, France; Martin Scott, UCL European Research \& Innovation Office, UK.",

year = "2017",

month = oct,

day = "1",

doi = "10.1093/jac/dkx247",

language = "English",

volume = "72",

pages = "2862--2868",

journal = "Journal of Antimicrobial Chemotherapy",

issn = "0305-7453",

publisher = "Oxford University Press",

number = "10",

}

TY - JOUR

T1 - CD4 T cell decline following HIV seroconversion in individuals with and without CXCR4-tropic virus

AU - on behalf of the CASCADE Collaboration in EuroCoord

AU - Ghosn, Jade

AU - Bayan, Tatiana

AU - Meixenberger, Karolin

AU - Tran, Laurent

AU - Frange, Pierre

AU - Monforte, Antonella d.Arminio

AU - Zangerle, Robert

AU - de Mendoza, Carmen

AU - Krastinova, Evguenia

AU - Porter, Kholoud

AU - Meyer, Laurence

AU - Chaix, Marie Laure

AU - Burns, Fiona

AU - Chene, Geneviève

AU - Costagliola, Dominique

AU - Giaquinto, Carlo

AU - Grarup, Jesper

AU - Kirk, Ole

AU - Meyer, Laurence

AU - Bailey, Heather

AU - Anne, Alain Volny

AU - Panteleev, Alex

AU - Phillips, Andrew

AU - Thorne, Claire

AU - Aboulker, Jean Pierre

AU - Albert, Jan

AU - Asandi, Silvia

AU - Cene, Geneviève

AU - Costagliola, Dominique

AU - Monforte, Antonella d.Arminio

AU - De Wit, Stéphane

AU - Reiss, Peter

AU - Del Amo, Julia

AU - Gatell, José

AU - Giaquinto, Carlo

AU - Hamouda, Osamah

AU - Karpov, Igor

AU - Ledergerber, Bruno

AU - Lundgren, Jens

AU - Malyuta, Ruslan

AU - Møller, Claus

AU - Prins, Maria

AU - Rakhmanova, Aza

AU - Rockstroh, Jürgen

AU - Rosinska, Magda

AU - Sandhu, Manjinder

AU - Thorne, Claire

AU - Touloumi, Giota

AU - Anne, Alain Volny

AU - Fenton, Kevin

N1 - Funding Information: This study was funded by the CASCADE collaboration in EuroCOORD. CASCADE Steering Committee Julia Del Amo (Chair), Laurence Meyer (Vice Chair), Heiner C. Bucher, Geneviève Chêne, Osamah Hamouda, Deenan Pillay, Maria Prins, Magda Rosinska, Caroline Sabin and Giota Touloumi. CASCADE Co-Ordinating Centre Kholoud Porter (Project Leader), Ashley Olson, Andrea Cartier, Lorraine Fradette, Sarah Walker and Abdel Babiker. CASCADE Clinical Advisory Board Heiner C. Bucher, Andrea De Luca, Martin Fisher, Roberto Muga. CASCADE Collaborators Australia PHAEDRA cohort (Tony Kelleher, David Cooper, Pat Grey, Robert Finlayson, Mark Bloch) Sydney AIDS Prospective Study and Sydney Primary HIV Infection cohort (Tony Kelleher, Tim Ramacciotti, Linda Gelgor, David Cooper, Don Smith); Austria Austrian HIV Cohort Study (Robert Zangerle); Canada South Alberta clinic (John Gill); Estonia Tartu Ülikool (Irja Lutsar); France ANRS CO3 Aquitaine cohort (Geneviève Chêne, Francois Dabis, Rodolphe Thiebaut), ANRS CO4 French Hospital Database (Dominique Costagliola, Marguerite Guiguet), Lyon Primary Infection cohort (Philippe Vanhems), French ANRS CO6 PRIMO cohort (Marie-Laure Chaix, Jade Ghosn), ANRS CO2 SEROCO cohort (Laurence Meyer, Faroudy Boufassa); Germany German HIV-1 seroconverter cohort (Osamah Hamouda, Karolin Meixenberger, Norbert Bannert, Barbara Bartmeyer); Greece AMACS (Anastasia Antoniadou, Georgios Chrysos, Georgios L. Daikos); Greek Haemophilia cohort (Giota Touloumi, Nikos Pantazis, Olga Katsarou); Italy Italian Seroconversion Study (Giovanni Rezza, Maria Dorrucci), ICONA cohort (Antonella d'Arminio Monforte, Andrea De Luca); Netherlands Amsterdam Cohort Studies among homosexual men and drug users (Maria Prins, Ronald Geskus, Jannie van der Helm, Hanneke Schuitemaker); Norway Oslo and Ulleval Hospital cohorts (Mette Sannes, Oddbjorn Brubakk, Anne-Marte Bakken Kran); Poland National Institute of Hygiene (Magdalena Rosinska); Spain Badalona IDU hospital cohort (Roberto Muga, Jordi Tor), Barcelona IDU Cohort (Patricia Garcia de Olalla, Joan Cayla), CoRIS-scv (Julia del Amo, Santiago Moreno, Susana Monge); Madrid cohort (Julia Del Amo, Jorge del Romero), Valencia IDU cohort (Santiago Pérez-Hoyos); Sweden Swedish InfCare HIV Cohort, Sweden (Anders Sönnerborg); Switzerland Swiss HIV Cohort Study (Heiner C. Bucher, Huldrych Günthard, Alexandra Scherrer); Ukraine Perinatal Prevention of AIDS Initiative (Ruslan Malyuta); United Kingdom Public Health England (Gary Murphy), UK Register of HIV Seroconverters (Kholoud Porter, Anne Johnson, Andrew Phillips, Abdel Babiker), University College London (Deenan Pillay); African cohorts: Genital Shedding Study (US: Charles Morrison; Family Health International, Robert Salata, Case Western Reserve University, Uganda: Roy Mugerwa, Makerere University, Zimbabwe: Tsungai Chipato, University of Zimbabwe); International AIDS Vaccine Initiative (IAVI) Early Infections Cohort (Kenya, Rwanda, South Africa, Uganda, Zambia: Matt A. Price, IAVI, USA; Jill Gilmour, IAVI, UK; Anatoli Kamali, IAVI, Kenya; Etienne Karita, Projet San Francisco, Rwanda). EuroCoord Executive Board Fiona Burns, University College London, UK; Geneviève Ch^ene, University of Bordeaux, France; Dominique Costagliola (Scientific Coordinator), Institut National de la Santé et de la Recherche Médicale, France; Carlo Giaquinto, Fondazione PENTA, Italy; Jesper Grarup, Region Hovedstaden, Denmark; Ole Kirk, Region Hovedstaden, Denmark; Laurence Meyer, Institut National de la Santé et de la Recherche Médicale, France; Heather Bailey, University College London, UK; Alain Volny Anne, European AIDS Treatment Group, France; Alex Panteleev, St Petersburg City AIDS Centre, Russian Federation; Andrew Phillips, University College London, UK, Kholoud Porter, University College London, UK; Claire Thorne, University College London, UK. EuroCoord Council of Partners Jean-Pierre Aboulker, Institut National de la Santé et de la Recherche Médicale, France; Jan Albert, Karolinska Institute, Sweden; Silvia Asandi, Romanian Angel Appeal Foundation, Romania; Geneviève Chêne, University of Bordeaux, France; Dominique Costagliola (chair), INSERM, France; Antonella d'Arminio Monforte, ICoNA Foundation, Italy; Stéphane De Wit, St Pierre University Hospital, Belgium; Peter Reiss, Stichting HIV Monitoring, Netherlands; Julia Del Amo, Instituto de Salud Carlos III, Spain; José Gatell, Fundació Privada Clínic per a la Recerca Bíomèdica, Spain; Carlo Giaquinto, Fondazione PENTA, Italy; Osamah Hamouda, Robert Koch Institut, Germany; Igor Karpov, University of Minsk, Belarus; Bruno Ledergerber, University of Zurich, Switzerland; Jens Lundgren, Region Hovedstaden, Denmark; Ruslan Malyuta, Perinatal Prevention of AIDS Initiative, Ukraine; Claus Møller, Cadpeople A/S, Denmark; Kholoud Porter, University College London, United Kingdom; Maria Prins, Academic Medical Centre, Netherlands; Aza Rakhmanova, St Petersburg City AIDS Centre, Russian Federation; Jürgen Rockstroh, University of Bonn, Germany; Magda Rosinska, National Institute of Public Health, National Institute of Hygiene, Poland; Manjinder Sandhu, Genome Research Limited; Claire Thorne, University College London, UK; Giota Touloumi, National and Kapodistrian University of Athens, Greece; Alain Volny Anne, European AIDS Treatment Group, France. EuroCoord External Advisory Board David Cooper, University of New South Wales, Australia; Nikos Dedes, Positive Voice, Greece; Kevin Fenton, Public Health England, USA; David Pizzuti, Gilead Sciences, USA; Marco Vitoria, WHO, Switzerland. EuroCoord Secretariat Silvia Faggion, Fondazione PENTA, Italy; Lorraine Fradette, University College London, UK; Richard Frost, University College London, UK; Andrea Cartier, University College London, UK; Dorthe Raben, Region Hovedstaden, Denmark; Christine Schwimmer, University of Bordeaux, France; Martin Scott, UCL European Research & Innovation Office, UK.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Background: THe natural clinical and immunological courses following HIV seroconversion with CXCR4-tropic or dual-mixed (X4/DM) viruses are controversial. We compared spontaneous immunological outcome in patients harbouring an X4/DM virus at the time of seroconversion with those harbouring a CCR5-tropic (R5) virus. Methods: Data were included from patients participating in CASCADE, a large cohort collaboration of HIV seroconverters, with ≥ 2 years of follow-up since seroconversion. The HIV envelope gene was sequenced from frozen plasma samples collected at enrolment, and HIV tropismwas determined using Geno 2Pheno (false-positive rate 10%). The spontaneous CD4 T cell evolution was compared by modelling CD4 kinetics using linear mixed-effects models with random intercept and random slope. Results: A total of 1387 patients were eligible. Median time between seroconversion and enrolment was 1month (range 0-3). At enrolment, 202 of 1387 (15%) harboured an X4/DM-tropic virus. CD4 decrease slopes were not significantly different according to HIV-1 tropism during the first 30months after seroconversion. No marked change in these results was found after adjusting for age, year of seroconversion and baseline HIV viral load. Time to antiretroviral treatment initiation was not statistically different between patients harbouring an R5 (20.76months) and those harbouring an X4/DM-tropic virus (22.86months, logrank test P"0.32). Conclusions: In this large cohort collaboration, 15% of the patients harboured an X4/DM virus close to HIV seroconversion. Patients harbouring X4/DM-tropic viruses close to seroconversion did not have an increased risk of disease progression, estimated by the decline in CD4 T cell count or time to combined ART initiation.

AB - Background: THe natural clinical and immunological courses following HIV seroconversion with CXCR4-tropic or dual-mixed (X4/DM) viruses are controversial. We compared spontaneous immunological outcome in patients harbouring an X4/DM virus at the time of seroconversion with those harbouring a CCR5-tropic (R5) virus. Methods: Data were included from patients participating in CASCADE, a large cohort collaboration of HIV seroconverters, with ≥ 2 years of follow-up since seroconversion. The HIV envelope gene was sequenced from frozen plasma samples collected at enrolment, and HIV tropismwas determined using Geno 2Pheno (false-positive rate 10%). The spontaneous CD4 T cell evolution was compared by modelling CD4 kinetics using linear mixed-effects models with random intercept and random slope. Results: A total of 1387 patients were eligible. Median time between seroconversion and enrolment was 1month (range 0-3). At enrolment, 202 of 1387 (15%) harboured an X4/DM-tropic virus. CD4 decrease slopes were not significantly different according to HIV-1 tropism during the first 30months after seroconversion. No marked change in these results was found after adjusting for age, year of seroconversion and baseline HIV viral load. Time to antiretroviral treatment initiation was not statistically different between patients harbouring an R5 (20.76months) and those harbouring an X4/DM-tropic virus (22.86months, logrank test P"0.32). Conclusions: In this large cohort collaboration, 15% of the patients harboured an X4/DM virus close to HIV seroconversion. Patients harbouring X4/DM-tropic viruses close to seroconversion did not have an increased risk of disease progression, estimated by the decline in CD4 T cell count or time to combined ART initiation.

UR - https://www.scopus.com/pages/publications/85030693513

U2 - 10.1093/jac/dkx247

DO - 10.1093/jac/dkx247

M3 - Article

C2 - 29091208

AN - SCOPUS:85030693513

SN - 0305-7453

VL - 72

SP - 2862

EP - 2868

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 10

ER -

CD4 T cell decline following HIV seroconversion in individuals with and without CXCR4-tropic virus

Abstract

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