The CD4/CD8 ratio in HIV-infected subjects is independently associated with T-cell activation despite long-term viral suppression
HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the biological significance of this finding. Cross-sectional analysis in 20 HIV-infected subjects on stable triple-ART, plasma HIV RNA <40 copies/mL for a...
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| Published in | The Journal of infection Vol. 66; no. 1; pp. 57 - 66 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Amsterdam
Elsevier Ltd
01.01.2013
Elsevier |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0163-4453 1532-2742 1532-2742 |
| DOI | 10.1016/j.jinf.2012.09.013 |
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| Abstract | HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the biological significance of this finding.
Cross-sectional analysis in 20 HIV-infected subjects on stable triple-ART, plasma HIV RNA <40 copies/mL for at least 2 years and CD4 count >350 cells/mm3. Laboratory measurements included T-cell activation (HLADR+, CD38+) and senescence (CD57+), lipopolysaccharide (LPS), sCD14 and the HIV latent reservoir (number of latently infected memory CD4 cells carrying replication-competent virus).
CD4/CD8 ratio was positively correlated with CD4 nadir (r = 0.468, p = 0.038) and accumulated ART exposure (r = 0.554, p = 0.0011), and negatively with viral load before ART initiation (r = −0.547, p = 0.013), CD4+HLADR+CD38+ T-cells (r = −0.428, p = 0.086) and CD8+CD57+ T-cells (r = −0.431, p = 0.084). No associations with LPS, sCD14 or HIV latent reservoir were found. After the multivariate analyses, the CD4/CD8 ratio remained independently associated with CD4+HLADR+CD38+ T-cells and CD8+HLADR+ T-cells.
In our study in subjects on suppressive ART the CD4/CD8 ratio was independently associated with T-cell activation. Our results must be confirmed in larger studies, as this parameter might be a useful clinical tool to identify subjects with ongoing immune activation despite long-term viral suppression. |
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| AbstractList | HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the biological significance of this finding.
Cross-sectional analysis in 20 HIV-infected subjects on stable triple-ART, plasma HIV RNA <40 copies/mL for at least 2 years and CD4 count >350 cells/mm3. Laboratory measurements included T-cell activation (HLADR+, CD38+) and senescence (CD57+), lipopolysaccharide (LPS), sCD14 and the HIV latent reservoir (number of latently infected memory CD4 cells carrying replication-competent virus).
CD4/CD8 ratio was positively correlated with CD4 nadir (r = 0.468, p = 0.038) and accumulated ART exposure (r = 0.554, p = 0.0011), and negatively with viral load before ART initiation (r = −0.547, p = 0.013), CD4+HLADR+CD38+ T-cells (r = −0.428, p = 0.086) and CD8+CD57+ T-cells (r = −0.431, p = 0.084). No associations with LPS, sCD14 or HIV latent reservoir were found. After the multivariate analyses, the CD4/CD8 ratio remained independently associated with CD4+HLADR+CD38+ T-cells and CD8+HLADR+ T-cells.
In our study in subjects on suppressive ART the CD4/CD8 ratio was independently associated with T-cell activation. Our results must be confirmed in larger studies, as this parameter might be a useful clinical tool to identify subjects with ongoing immune activation despite long-term viral suppression. Objectives: HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the biological significance of this finding. Methods: Cross-sectional analysis in 20 HIV-infected subjects on stable triple-ART, plasma HIV RNA 350ANBcells/mm3. Laboratory measurements included T-cell activation (HLADR+, CD38+) and senescence (CD57+), lipopolysaccharide (LPS), sCD14 and the HIV latent reservoir (number of latently infected memory CD4 cells carrying replication-competent virus). Results: CD4/CD8 ratio was positively correlated with CD4 nadir (rANB=ANB0.468, pANB=ANB0.038) and accumulated ART exposure (rANB=ANB0.554, pANB=ANB0.0011), and negatively with viral load before ART initiation (rANB=ANB-0.547, pANB=ANB0.013), CD4+HLADR+CD38+ T-cells (rANB=ANB-0.428, pANB=ANB0.086) and CD8+CD57+ T-cells (rANB=ANB-0.431, pANB=ANB0.084). No associations with LPS, sCD14 or HIV latent reservoir were found. After the multivariate analyses, the CD4/CD8 ratio remained independently associated with CD4+HLADR+CD38+ T-cells and CD8+HLADR+ T-cells. Conclusions: In our study in subjects on suppressive ART the CD4/CD8 ratio was independently associated with T-cell activation. Our results must be confirmed in larger studies, as this parameter might be a useful clinical tool to identify subjects with ongoing immune activation despite long-term viral suppression. Summary Objectives HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the biological significance of this finding. Methods Cross-sectional analysis in 20 HIV-infected subjects on stable triple-ART, plasma HIV RNA <40 copies/mL for at least 2 years and CD4 count >350 cells/mm3 . Laboratory measurements included T-cell activation (HLADR+ , CD38+ ) and senescence (CD57+ ), lipopolysaccharide (LPS), sCD14 and the HIV latent reservoir (number of latently infected memory CD4 cells carrying replication-competent virus). Results CD4/CD8 ratio was positively correlated with CD4 nadir ( r = 0.468, p = 0.038) and accumulated ART exposure ( r = 0.554, p = 0.0011), and negatively with viral load before ART initiation ( r = −0.547, p = 0.013), CD4+ HLADR+ CD38+ T-cells ( r = −0.428, p = 0.086) and CD8+ CD57+ T-cells ( r = −0.431, p = 0.084). No associations with LPS, sCD14 or HIV latent reservoir were found. After the multivariate analyses, the CD4/CD8 ratio remained independently associated with CD4+ HLADR+ CD38+ T-cells and CD8+ HLADR+ T-cells. Conclusions In our study in subjects on suppressive ART the CD4/CD8 ratio was independently associated with T-cell activation. Our results must be confirmed in larger studies, as this parameter might be a useful clinical tool to identify subjects with ongoing immune activation despite long-term viral suppression. HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the biological significance of this finding.OBJECTIVESHIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the biological significance of this finding.Cross-sectional analysis in 20 HIV-infected subjects on stable triple-ART, plasma HIV RNA <40 copies/mL for at least 2 years and CD4 count >350 cells/mm(3). Laboratory measurements included T-cell activation (HLADR(+), CD38(+)) and senescence (CD57(+)), lipopolysaccharide (LPS), sCD14 and the HIV latent reservoir (number of latently infected memory CD4 cells carrying replication-competent virus).METHODSCross-sectional analysis in 20 HIV-infected subjects on stable triple-ART, plasma HIV RNA <40 copies/mL for at least 2 years and CD4 count >350 cells/mm(3). Laboratory measurements included T-cell activation (HLADR(+), CD38(+)) and senescence (CD57(+)), lipopolysaccharide (LPS), sCD14 and the HIV latent reservoir (number of latently infected memory CD4 cells carrying replication-competent virus).CD4/CD8 ratio was positively correlated with CD4 nadir (r = 0.468, p = 0.038) and accumulated ART exposure (r = 0.554, p = 0.0011), and negatively with viral load before ART initiation (r = -0.547, p = 0.013), CD4(+)HLADR(+)CD38(+) T-cells (r = -0.428, p = 0.086) and CD8(+)CD57(+) T-cells (r = -0.431, p = 0.084). No associations with LPS, sCD14 or HIV latent reservoir were found. After the multivariate analyses, the CD4/CD8 ratio remained independently associated with CD4(+)HLADR(+)CD38(+) T-cells and CD8(+)HLADR(+) T-cells.RESULTSCD4/CD8 ratio was positively correlated with CD4 nadir (r = 0.468, p = 0.038) and accumulated ART exposure (r = 0.554, p = 0.0011), and negatively with viral load before ART initiation (r = -0.547, p = 0.013), CD4(+)HLADR(+)CD38(+) T-cells (r = -0.428, p = 0.086) and CD8(+)CD57(+) T-cells (r = -0.431, p = 0.084). No associations with LPS, sCD14 or HIV latent reservoir were found. After the multivariate analyses, the CD4/CD8 ratio remained independently associated with CD4(+)HLADR(+)CD38(+) T-cells and CD8(+)HLADR(+) T-cells.In our study in subjects on suppressive ART the CD4/CD8 ratio was independently associated with T-cell activation. Our results must be confirmed in larger studies, as this parameter might be a useful clinical tool to identify subjects with ongoing immune activation despite long-term viral suppression.CONCLUSIONSIn our study in subjects on suppressive ART the CD4/CD8 ratio was independently associated with T-cell activation. Our results must be confirmed in larger studies, as this parameter might be a useful clinical tool to identify subjects with ongoing immune activation despite long-term viral suppression. HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the biological significance of this finding. Cross-sectional analysis in 20 HIV-infected subjects on stable triple-ART, plasma HIV RNA <40 copies/mL for at least 2 years and CD4 count >350 cells/mm(3). Laboratory measurements included T-cell activation (HLADR(+), CD38(+)) and senescence (CD57(+)), lipopolysaccharide (LPS), sCD14 and the HIV latent reservoir (number of latently infected memory CD4 cells carrying replication-competent virus). CD4/CD8 ratio was positively correlated with CD4 nadir (r = 0.468, p = 0.038) and accumulated ART exposure (r = 0.554, p = 0.0011), and negatively with viral load before ART initiation (r = -0.547, p = 0.013), CD4(+)HLADR(+)CD38(+) T-cells (r = -0.428, p = 0.086) and CD8(+)CD57(+) T-cells (r = -0.431, p = 0.084). No associations with LPS, sCD14 or HIV latent reservoir were found. After the multivariate analyses, the CD4/CD8 ratio remained independently associated with CD4(+)HLADR(+)CD38(+) T-cells and CD8(+)HLADR(+) T-cells. In our study in subjects on suppressive ART the CD4/CD8 ratio was independently associated with T-cell activation. Our results must be confirmed in larger studies, as this parameter might be a useful clinical tool to identify subjects with ongoing immune activation despite long-term viral suppression. |
| Author | Dronda, Fernando Hernández-Novoa, Beatriz Serrano-Villar, Sergio Muñoz-Fernández, María Ángeles Moreno, Santiago Gutiérrez, Carolina Madrid, Nadia Díaz, Laura Abad Fernández, María Zamora, Javier Vallejo, Alejandro |
| Author_xml | – sequence: 1 givenname: Sergio surname: Serrano-Villar fullname: Serrano-Villar, Sergio email: serranovillar@gmail.com organization: Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain – sequence: 2 givenname: Carolina surname: Gutiérrez fullname: Gutiérrez, Carolina organization: Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain – sequence: 3 givenname: Alejandro surname: Vallejo fullname: Vallejo, Alejandro organization: Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain – sequence: 4 givenname: Beatriz surname: Hernández-Novoa fullname: Hernández-Novoa, Beatriz organization: Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain – sequence: 5 givenname: Laura surname: Díaz fullname: Díaz, Laura organization: Inmunobiology Laboratory, Hospital General Universitario Gregorio Marañón, Madrid, Spain – sequence: 6 givenname: María surname: Abad Fernández fullname: Abad Fernández, María organization: Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain – sequence: 7 givenname: Nadia surname: Madrid fullname: Madrid, Nadia organization: Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain – sequence: 8 givenname: Fernando surname: Dronda fullname: Dronda, Fernando organization: Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain – sequence: 9 givenname: Javier surname: Zamora fullname: Zamora, Javier organization: Biostatistics Department, Hospital Universitario Ramón y Cajal, Madrid, Spain – sequence: 10 givenname: María Ángeles surname: Muñoz-Fernández fullname: Muñoz-Fernández, María Ángeles organization: Inmunobiology Laboratory, Hospital General Universitario Gregorio Marañón, Madrid, Spain – sequence: 11 givenname: Santiago surname: Moreno fullname: Moreno, Santiago email: smoreno.hrc@salud.madrid.org organization: Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26780505$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/23046968$$D View this record in MEDLINE/PubMed |
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| Keywords | HIV CD4/CD8 ratio Immunosenescence Immune activation HIV-1 latent reservoir CD4 count Bacterial translocation Infection Immunopathology Immunological investigation Viral disease T-Lymphocyte AIDS Immune deficiency Long term |
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| Snippet | HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the biological... Summary Objectives HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to... Objectives: HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the... |
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| SubjectTerms | Adult Anti-Retroviral Agents - therapeutic use antiretroviral therapy Bacterial Translocation Biological and medical sciences CD4 antigen CD4 count CD4-CD8 Ratio CD57 antigen CD8 antigen Clinical Trials, Phase II as Topic Cross-Sectional Studies Cyclohexanes - therapeutic use Female General aspects Histocompatibility antigen HLA HIV HIV Infections - drug therapy HIV Infections - immunology HIV Infections - microbiology HIV-1 latent reservoir Host-Pathogen Interactions Human immunodeficiency virus Human viral diseases Humans Immune activation Immune response Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunological memory Immunopathology Immunosenescence Infectious Disease Infectious diseases Latent infection Lipopolysaccharides Lymphocyte Activation Lymphocytes T Male Medical sciences Middle Aged Multivariate Analysis Pyrrolidinones - therapeutic use Raltegravir Potassium Risk Factors RNA Senescence Statistics, Nonparametric T-Lymphocytes - immunology Triazoles - therapeutic use Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Load |
| Title | The CD4/CD8 ratio in HIV-infected subjects is independently associated with T-cell activation despite long-term viral suppression |
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