Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy: Collaborative Study of Treatment Programs

The IeDEA and COHERE Cohort Collaborations

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Abstract

Background. Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodefciency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively). Methods. We included HIV-infected individuals aged =16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-e?ect models were used to smooth trends in median CD4 cell counts. Results. A total of 951 855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/μL (95% confdence interval, 58-104/μL) to 287/μL (250-328/μL) in LICs, from 99/μL (71-140/μL) to 234/μL (192-285/μL) in LMICs, from 71/μL (49-104/μL) to 311/μL (255-379/μL) in UMICs, and from 161/μL (143-181/μL) to 327/μL (286-372/μL) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed. Conclusions. Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/μL in 2015. Substantial additional e?orts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART.

Original languageEnglish
Pages (from-to)893-903
Number of pages11
JournalClinical Infectious Diseases
Volume66
Issue number6
DOIs
Publication statusPublished - 5 Mar 2018

Bibliographical note

Funding Information:
Potential conflicts of interest. K. N. A. is a board member of TrioHealth and has received grants and other financial support from the NIH and Gilead Sciences. K. A. has received grants and other financial support from NIAID, Brown University, and the NIH. A. A. has received consultancy fees, grants or travel expenses from Gilead Sciences, BMS, ViiV Healthcare, Merck, Janssen Cilag, and Abbvie. B. C. has received grants and financial support from Infectious Disease Institute and the NIH. G. C. has received grants and other support from ANRS and the European Commission (FP7/2007–2013). I. J. C. has received grants from NHS England. D. C. was a member of the HIV board of Gilead France until December 2015 and has received consultancy fees, grants, and other financial support from Innavirvax, Janssen-Cilag, Merck Sharp & Dohme–Chibret, ViiV, and Gilead. A. d. M. was a board member of Gilead, Jansen, Merck Sharp & Dohme (MSD), and ViiV. S. D. W. has received consultancy fees, grants, or other financial support from ViiV, MSD, Gilead, Janssen, and BMS. K. G.-P. is a board member of Gilead Sciences and has received financial support from BMS, Gilead Sciences, and GSK-ViiV. O. K. is a board member for Gilead and ViiV and has received financial support from Gilead, BMS, and ViiV. L. M. has received grants and other financial support from ANRS, Framework Program 7 through Medical Research Council. C. M. is a board member for MSD, Gilead, BMS, and ViiV and has received grants and other financial support from Gilead, ViiV, Janssen, and MSD. P. R. is a board member for Gilead Sciences and Janssen Pharmaceutica and has received grants and other financial support from Gilead, ViiV, Janssen, and Merck & Co. C. S. is a board member for ViiV, Gilead, and Janssen-Cilag and has received grants or financial support from MRC, Gilead, ViiV, and Janssen-Cilag. A. S. has received consultancy fees, grants and other financial support from Immune System Regulation AB, Octapharma, Gilead, Jansen-Cilag, BMS, and GlaxoSmithKline/ViiV. M. S. is a board member for Abbvie, Janssen Cilag, MSD, Gilead, and ViiV and has received consultancy fees or grants from Roche, Gilead, Janssen Cilag, and MSD. C. T. has received grants from the European Commission, Abbvie, Public Health England, and the Medical Research Council. C. T. has received reimbursement of expenses for participation to international conferences from Gilead. J.-C. W. has received financial support from Gilead, Abbvie, and MSD. L. W. was a board member of BMS until 2015 and has received grants from ANRS and payments for lectures from Gilead and Janssen. B. C.-R. has received financial support from Janssen, MSD, Abbvie, and Gilead. M.-A. D. has received grants from the NIH, International AIDS Society, and the CDC. N. L. D. L. M. has received financial support from the NIH, the University of Sydney, and the NSW Ministry of Health. M. L. has received grants and other financial support from Gilead Sciences, Boehringer Ingelheim, MSD, BMS, Janssen-Cilag, ViiV HealthCare, and Sirtex. R. M. has received payments from Medscape. O. T. N. has received grants from Singapore Medical Research Council. L. R. and K. W.-K. have received grants from the CDC and the NIH. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Funding Information:
Financial support. The African regions for IeDEA are supported by the National Cancer Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Allergy and Infectious Diseases (NIAID) as part of the IeDEA (grants U01AI069919, U01AI069924, U01AI096299, and U01AI069911). The Caribbean, Central, and South America Network for HIV Epidemiology (CCASAnet), a member cohort of IeDEA (grant U01AI069923), is funded by the following institutes: NICHD, Office of the Director, NIH, NIAID, the National Cancer Institute, and the National Institute of Mental Health. The North American AIDS Cohort Collaboration on Research and Design of IeDEA is supported by the NIH (grants U01AI069918, F31DA037788, G12MD007583, K01AI093197, K23EY013707, K24AI065298, K24AI118591, K24DA000432, KL2TR000421, M01RR000052, N01CP01004, N02CP055504, N02CP91027, P30AI027757, P30AI027763, P30AI027767, P30AI036219, P30AI050410, P30AI094189, P30AI110527, P30MH62246, R01AA016893, R01AG053100, R01CA165937, R01DA011602, R01DA012568, R24AI067039, U01AA013566, U01AA020790, U01AI031834, U01AI034989, U01AI034993, U01AI034994, U01AI035004, U01AI035039, U01AI035040, U01AI035041, U01AI035042, U01AI037613, U01AI037984, U01AI038855, U01AI038858, U01AI042590, U01AI068634, U01AI068636, U01AI069432, U01AI069434, U01AI103390, U01AI103397, U01AI103401, U01AI103408, U01DA03629, U01DA036935, U01HD032632, U10EY008057, U10EY008052, U10EY008067, U24AA020794, U54MD007587, UL1RR024131, UL1TR000004, UL1TR000083, UL1TR000454, UM1AI035043, Z01CP010214, and Z01CP010176); the US Centers for Disease Control and Prevention (CDC; contracts CDC-200-2006-18797 and CDC-200-2015-63931); from the US Agency for Healthcare Research and Quality (contract 90047713); from the US Health Resources and Services Administration (contract 90051652); the Canadian Institutes of Health Research (grants CBR-86906, CBR-94036, HCP-97105, and TGF-96118); Ontario Ministry of Health and Long Term Care; and the Government of Alberta, Canada. Additional support was provided by the National Cancer Institute, National Institute for Mental Health, and National Institute on Drug Abuse. The TREAT Asia HIV Observational Database and the Australian HIV Observational Database are initiatives of TREAT Asia, a program of amfAR, The Foundation for AIDS Research, with support from the NIAID, the NICHD, the National Cancer Institute, the National Institute of Mental Health, and the National Institute on Drug Abuse, as part of IeDEA (grant U01AI069907). The Kirby Institute is funded by the Australian Government Department of Health and Ageing and affiliated with the Faculty of Medicine, UNSW Sydney.

Funding Information:
The COHERE study group has received unrestricted funding from Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS), France; the HIV Monitoring Foundation, the Netherlands; and the Augustinus Foundation, Denmark. The research leading to these results received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under EuroCoord grant agreement 260694. Icona Foundation is sponsored by unrestricted grants from Gilead, Bristol-Myers Squibb (BMS), ViiV, and MSD Italy. ANRS HIV cohorts are funded by ANRS. The Collaborative HIV Paediatric Study is funded by NHS England and has received additional support from the PENTA Foundation and the Medical Research Council programme (MC_UU_12023/26), as well as Abbott, Boehringer Ingelheim, BMS, Gilead Sciences, GlaxoSmithKline, Janssen, and Roche. A list of other funders of the participating cohorts can be found at www.cohere.org.

Publisher Copyright:
© 2017 The Author(s).

Keywords

  • CD4 cell count
  • WHO guidelines
  • antiretroviral therapy

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