Absolute CD4 +  T cell count overstate immune recovery assessed by CD4 + /CD8 +  ratio in HIV-infected patients on treatment

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Abstract

Objectives

To analyse the correlation and concordance between aCD4, CD4%, CD4/CD8, their intra-patient variability, and to compare the immune recovery (IR) rates based on the three parameters in HIV-infected patients after starting antiretroviral therapy.

Methods

From a prospectively followed cohort, patients who maintained HIV-RNA suppression in ≥95% of the determinations throughout the follow-up were selected. IR was defined as aCD4 >650/μl, CD4% ≥38% or CD4/CD8 ≥1.

Results

A total of 1164 patients with a median follow-up of 5 years were analysed. The increases in aCD4, CD4% and CD4/CD8 were highest during the first year and considerably lower thereafter regardless of baseline aCD4. The annual increases in aCD4 showed poor correlations with those of CD4% (r = 0.143–0.250) and CD4/CD8 (r = 0.101–0.192) but were high between CD4% and CD4/CD8 (r = 0.765–0.844; p<0.001). The median intra-annual coefficients of variation for aCD4, CD4/CD8 and CD4% were 12.5, 8.5 and 6.6, respectively. After five years, 66.7%, 41.6% and 42.1% of the patients reached aCD4 >650/μl, CD4% ≥38%, and CD4/CD8 ≥1, respectively, while only 31% achieved both aCD4 and CD4/CD8 target values.

Conclusions

The increases in aCD4 poorly correlate with those of CD4% and CD4/CD8. IR rates based on aCD4 significantly overstate those obtained by CD4% and CD4/CD8. CD4% and CD4/CD8 are more stable markers than aCD4 and should be taken into account to monitor the IR after treatment initiation.

Related collections

Most cited references 20

Record: found
Abstract: found
Article: not found

A concordance correlation coefficient to evaluate reproducibility.

L Lin (1989)

A new reproducibility index is developed and studied. This index is the correlation between the two readings that fall on the 45 degree line through the origin. It is simple to use and possesses desirable properties. The statistical properties of this estimate can be satisfactorily evaluated using an inverse hyperbolic tangent transformation. A Monte Carlo experiment with 5,000 runs was performed to confirm the estimate's validity. An application using actual data is given.

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Record: found
Abstract: found
Article: not found

Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational cohort study.

A Mocroft, AN Phillips, J Gatell … (2007)

Combination antiretroviral therapy (cART) has been shown to reduce mortality and morbidity in patients with HIV. As viral replication falls, the CD4 count increases, but whether the CD4 count returns to the level seen in HIV-negative people is unknown. We aimed to assess whether the CD4 count for patients with maximum virological suppression (viral load <50 copies per mL) continues to increase with long-term cART to reach levels seen in HIV-negative populations. We compared increases in CD4 counts in 1835 antiretroviral-naive patients who started cART from EuroSIDA, a pan-European observational cohort study. Rate of increase in CD4 count (per year) occurring between pairs of consecutive viral loads below 50 copies per mL was estimated using generalised linear models, accounting for multiple measurements for individual patients. The median CD4 count at starting cART was 204 cells per microL (IQR 85-330). The greatest mean yearly increase in CD4 count of 100 cells per microL was seen in the year after starting cART. Significant, but lower, yearly increases in CD4 count, around 50 cells per microL, were seen even at 5 years after starting cART in patients whose current CD4 count was less than 500 cells per microL. The only groups without significant increases in CD4 count were those where cART had been taken for more than 5 years with a current CD4 count of more than 500 cells per microL, (current mean CD4 count 774 cells per microL; 95% CI 764-783). Patients starting cART with low CD4 counts (<200 cells per microL) had significant rises in CD4 counts even after 5 years of cART. Normalisation of CD4 counts in HIV-infected patients for all infected individuals might be achievable if viral suppression with cART can be maintained for a sufficiently long period of time.

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CD4 cell counts of 800 cells/mm3 or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm3 or greater.

Azra C. Ghani, Frank Miedema, Mark I van Berge Henegouwen … (2007)

CD4 cell count changes in therapy-naive patients were investigated during 7 years of highly active antiretroviral therapy (HAART) in an observational cohort. Three endpoints were studied: (1) time to >or=800 CD4 cells/mm in 5299 therapy-naive patients starting HAART, (2) CD4 cell count changes during 7 years of uninterrupted HAART in a subset of 544 patients, and (3) reaching a plateau in CD4 cell restoration after 5 years of HAART in 366 virologically suppressed patients. Among patients with or=500 CD4 cells/mm at baseline, respectively, 20%, 26%, 46%, 73%, and 87% reached >or=800 CD4 cells/mm within 7 years of starting HAART. Periods with HIV RNA levels >500 copies/mL and age >or=50 years were associated with lesser increases in CD4 cell counts between 6 months and 7 years. Having reached >or=800 CD4 cells/mm at 5 years, age >or=50 years, and >or=1 HIV RNA measurement >1000 copies/mL between 5 and 7 years were associated with a plateau in CD4 cell restoration. Restoration to CD4 cell counts >or=800 cells/mm is feasible within 7 years of HAART in most HIV-infected patients starting with >or=350 cells/mm and achieving sufficient suppression of viral replication. Particularly in patients >or=50 years of age, it may be beneficial to start earlier than current guidelines recommend.

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Author and article information

Contributors

Yusnelkis Milanés-Guisado: Role: Data curationRole: Formal analysisRole: Writing – original draft

Alicia Gutiérrez-Valencia: Role: Data curationRole: Formal analysisRole: Writing – original draft

María Trujillo-Rodríguez: Role: InvestigationRole: Methodology

Nuria Espinosa: Role: Investigation

Pompeyo Viciana: Role: Investigation

Luis Fernando López-Cortés:

ORCID: http://orcid.org/0000-0002-3804-3458

Role: ConceptualizationRole: Project administrationRole: Writing – review & editing

Cristian Apetrei: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 22 October 2018

Publication date Collection: 2018

Volume: 13

Issue: 10

Electronic Location Identifier: e0205777

Affiliations

[001]Enfermedades Infecciosas, Microbiología Clínica y Medicina Preventiva. Instituto de Biomedicina de Sevilla/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla. Seville, Spain

University of Pittsburgh Centre for Vaccine Research, UNITED STATES

Author notes

Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: LFLC, NE and PV have received unrestricted research funding, consultancy fees, and lecture fees from and have served on the advisory boards of Abbott, Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

* E-mail: luisfernando@ 123456lopezcortes.net

Author information

Luis Fernando López-Cortés http://orcid.org/0000-0002-3804-3458

Article

Publisher ID: PONE-D-18-24758

DOI: 10.1371/journal.pone.0205777

PMC ID: 6197681

PubMed ID: 30346965

SO-VID: d135506d-f411-4bcc-adc2-235fd36d9646

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 22 August 2018

Date accepted : 1 October 2018

Page count

Figures: 2, Tables: 3, Pages: 14

Funding

Funded by: RIS

Award ID: D16/0025/0020-ISCIII-FEDER

Award Recipient :

ORCID: http://orcid.org/0000-0002-3804-3458

Luis Fernando López-Cortés

This work was supported by Red de Investigación en SIDA (RIS) RD16/0025/0020-ISCIII-FEDER to LFLC.

Custom metadata

Data Availability All relevant data are within the manuscript and its Supporting Information file.