Does rapid HIV disease progression prior to combination antiretroviral therapy hinder optimal CD4 + T-cell recovery once HIV-1 suppression is achieved?

Inma Jarrin*, Nikos Pantazis, Judith Dalmau, Andrew N. Phillips, Ashley Olson, Cristina Mussini, Faroudy Boufassa, Dominique Costagliola, Kholoud Porter, Juliá Blanco, Julia Del Amo, Javier Martinez-Picado, Genevieve Chene, Caroline Sabin, Sarah Walker, Martin Fisher, Tony Kelleher, David Cooper, Robert Finlayson, Mark BlochTim Ramacciotti, Linda Gelgor, Don Smith, Robert Zangerle, John Gill, Irja Lutsar, Francois Dabis, Rodolphe Thiebaut, Marguerite Guiguet, Philippe Vanhems, Marie Laure Chaix, Jade Ghosn, Laurence Meyer, Osamah Hamouda, Claudia Kucherer, Barbara Bartmeyer, Anastasia Antoniadou, Georgios Chrysos, Georgios L. Daikos, Giota Touloumi, Olga Katsarou, Giovanni Rezza, Maria Dorrucci, Antonella D.arminio Monforte, Andrea De Luca, Maria Prins, Ronald Geskus, Jannie Van Der Helm, Hanneke Schuitemaker, Mette Sannes, Oddbjorn Brubakk, Anne Marte Bakken Kran, Magdalena Rosinska, Roberto Muga, Jordi Tor, Patricia Garcia De Olalla, Joan Cayla, Santiago Moreno, Susana Monge, Jorge Del Romero, Santiago Perez-Hoyos, Anders Sonnerborg, Heiner C. Bucher, Huldrych Gunthard, Martin Rickenbach, Ruslan Malyuta, Gary Murphy, Anne Johnson, Abdel Babiker, Deenan Pillay, Charles Morrison, Robert Salata, Roy Mugerwa, Tsungai Chipato, Pauli N. Amornkul, Jill Gilmour, Anatoli Kamali, Etienne Karita, Fiona Burns, Carlo Giaquinto, Jesper Grarup, Ole Kirk, Heather Bailey, Alain Volny Anne, Alex Panteleev, Claire Thorne, Jean Pierre Aboulker, Jan Albert, Silvia Asandi, Stephane De Wit, Peter Reiss, Jose Gatell, Igor Karpov, Bruno Ledergerber, Jens Lundgren, Claus Møller, Aza Rakhmanova, Jurgen Rockstroh, Manjinder Sandhu, Nikos Dedes, Kevin Fenton, David Pizzuti, Marco Vitoria, Silvia Faggion, Lorraine Fradette, Richard Frost, Andrea Cartier, Dorthe Raben, Christine Schwimmer, Martin Scott

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Objective: This article compares trends in CD4 + T-cell recovery and proportions achieving optimal restoration (≥500cells/μl) after viral suppression following combination antiretroviral therapy (cART) initiation between rapid and nonrapid progressors. Methods: We included HIV-1 seroconverters achieving viral suppression within 6 months of cART. Rapid progressors were individuals experiencing at least one CD4 + less than 200cells/μl within 12 months of seroconverters before cART. We used piecewise linear mixed models and logistic regression for optimal restoration. Results: Of 4024 individuals, 294 (7.3%) were classified as rapid progressors. At the same CD4 + T-cell count at cART start (baseline), rapid progressors experienced faster CD4 + T-cell increases than nonrapid progressors in first month [difference (95% confidence interval) in mean increase/month (square root scale): 1.82 (1.61; 2.04)], which reversed to slightly slower increases in months 1-18 [-0.05 (-0.06; -0.03)] and no significant differences in 18-60 months [-0.003 (-0.01; 0.01)]. Percentage achieving optimal restoration was significantly lower for rapid progressors than nonrapid progressors at months 12 (29.2 vs. 62.5%) and 36 (47.1 vs. 72.4%) but not at month 60 (70.4 vs. 71.8%). These differences disappeared after adjusting for baseline CD4 + T-cell count: odds ratio (95% confidence interval) 0.86 (0.61; 1.20), 0.90 (0.38; 2.17) and 1.56 (0.55; 4.46) at months 12, 36 and 60, respectively. Conclusion: Among people on suppressive antiretroviral therapy, rapid progressors experience faster initial increases of CD4 + T-cell counts than nonrapid progressors, but are less likely to achieve optimal restoration during the first 36 months after cART, mainly because of lower CD4 + T-cell counts at cART initiation.

Original languageEnglish
Pages (from-to)2323-2333
Number of pages11
JournalAIDS
Volume29
Issue number17
DOIs
Publication statusPublished - 1 Nov 2015

Bibliographical note

Funding Information:
CASCADE Steering Committee: Julia Del Amo (Chair), Laurence Meyer (Vice Chair), Heiner C. Bucher, Geneviève Chene, Osamah Hamouda, Deenan Pillay, Maria Prins, Magda Rosinska, Caroline Sabin, Giota Touloumi. CASCADE Co-Ordinating Centre: Kholoud Porter (Project Leader), Ashley Olson, Andrea Cartier, Lorraine Fradette, Sarah Walker, 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, 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 Chene, 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, Claudia Kücherer, 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, Martin Rickenbach); 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: Pauli N. Amornkul, IAVI, USA; Jill Gilmour, IAVI, UK; Anatoli Kamali, Uganda Virus Research Institute/Medical Research Council Uganda; Etienne Karita, Projet San Francisco, Rwanda). EuroCoord Executive Board: Fiona Burns, University College London, UK; Geneviève Chene, 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 Chene, 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 Mller, 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, World Health Organisation, 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. Ethics: Austrian HIV Cohort Study: Ethik-Kommission der Medizinischen Universität Wien, Medizinische Universität Graz - Ethikkommission, Ethikkommission der Medizinischen Universität Innsbruck, Ethikkommission des Landes Oberö sterreich, Ethikkommission fÜ;r das Bundesland Salzburg; PHAEDRA cohort: St Vincent''s Hospital, Human Research Ethics Committee; Southern Alberta Clinic Cohort: Conjoint Health Research Ethics Board of the Faculties of Medicine, Nursing and Kinesiology, University of Calgary; Aquitaine Cohort: Commission Nationale de l''Informatique et des Libertés; French Hospital Database: Commission nationale de l''informatique et des libertés CNIL; French PRIMO Cohort: Comite Consultatif de Protection des Personnes dans la Recherché Biomedicale; SEROCO Cohort: Commission Nationale de l''Informatique et des Libertés (CNIL); German HIV-1 Seroconverter Study: Charité, University Medicine Berlin; AMACS: Bioethics & Deontology Committee of Athens University Medical School and the National Organization of Medicines; Greek Haemophilia Cohort: Bioethics & Deontology Committee of Athens University Medical School and the National Organization of Medicines; ICoNA cohort: San Paolo Hospital Ethic Committee; Italian Seroconversion Study: Comitato etico dell''Istituto Superiore di Sanita`; Amsterdam Cohort Studies in Homosexual Men and IDUs: Academic Medical Centre, University of Amsterdam; Oslo and Ulleval Hospital Cohorts: Regional komite for medisinsk forskningsetikk – Øst- Norge (REK 1); Badalona IDU Hospital Cohort: Comité Etico de Investigación Clínica del Hospital Universitari Germans Trias i Pujol; CoRIS-scv: Comité Etico de Investigación Clínica de La Rioja; Madrid Cohort: Ethics Committee of Universidad Miguel Hernandez de Elche; Valencia IDU Cohort: Comité Etico de Investigacio ´n Clínica del Hospital Dr Peset-Valencia; Swiss HIV Cohort Study: Kantonale Ethikkommission, spezialisierte Unter-kommission Innere Medizin, Ethikkommission beider Basel, Kantonale Ethikkommission Bern, Comité départemental d''éthique de médecine et médecine communautaire, Commission d''éthique de la recherche clinique, Université de Lausanne, Comitato etico cantonale, Ethikkommission des Kantons St.Gallen; UK Register of HIV Seroconverters: South Birmigham REC; Early Infection Cohorts: Kenya Medical Research Institute, Kenyatta National Hospital, Uganda Virus Research Institute Science and Ethics Committee, Uganda National Council for Science and Technology, Uganda Virus Research Institute Science and Ethics Committee, Uganda National Council for Science and Technology, University of Zambia Research Ethics Committee, Emory IRB, National Ethics Committee of Rwanda, University of Cape Town Research Ethics Committee, University of Kwazulu Natal Nelson R Mandela School of Medicine; Genital Shedding Study Cohort: University Hospitals of Cleveland, IRB for Human Investigation (CWRU), AIDS Research Committee (ARC), STD/AIDS Control Programme, Uganda Ministry of Health, Committee on Human Research (CHR), Office of Research Administration (UCSF), Biomedical Research & Training Institute (BRTI) – Zimbabwe, Institutional Review Office, Fred Hutchinson Cancer Research Center, Medical Research Council of Zimbabwe (MRCZ). Funding: This work was supported by the European Union Seventh Framework Programme (FP7/2007– 2013) under EuroCoord grant agreement n8 260694. Authors'' contributions: All authors were involved in the setting up of the cohort and conceptualized the design. J.M.-P., J.B., J. D., J.D.A. and I.J. asked the research question presented in this manuscript. All authors were involved in data collection. I.J. was responsible for statistical analyses and was supervised by N.P. I.J. and J.D.A. wrote the first draft of the article. All authors were involved in interpretation of the data and commented interim drafts. All authors have reviewed the final manuscript. I.J. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the analysis.

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Keywords

  • CD4 responses
  • HIV-viral suppression
  • rapid progression

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