Increased risk of serious non-AIDS-related events in HIV-infected subjects on antiretroviral therapy associated with a low CD4/CD8 ratio.
BACKGROUND
A low CD4/CD8 ratio has been identified in the general population as a hallmark of inmmunosenescence and a surrogate of all-cause mortality. We aimed to investigate in treated HIV-infected individuals the relationship between the CD4/CD8 ratio and serious non-AIDS events.


METHODS
Case-control study within a prospective hospital-based cohort of HIV-infected subjects during at least one year of ART-mediated viral suppression. Cases were patients with serious non-AIDS events (non-AIDS malignancies, cardiovascular disease, and end-stage kidney disease), and controls individuals who did not developed non-AIDS events during follow-up. Data were analyzed using ROC analysis and multivariate logistic regression. Conditional logistic regression was performed in 200 cases/controls matched by age, sex, nadir CD4 and proximal CD4 counts.


RESULTS
We analyzed 407 subjects (109 cases, 298 controls). The CD4/CD8 ratio was lower in cases (0.44 vs. 0.70, P<0.0001), with higher discriminatory ability for the detection of non-AIDS events than the CD4 count, CD8 count and nadir CD4. Multivariate analyses (adjusted for age, sex, nadir CD4, proximal CD4 count, year of ART initiation and ART duration) confirmed the independent association of a low CD4/CD8 ratio with the risk of non-AIDS morbidity (per CD4/CD8 ratio quartile decrease, OR, 2.9; 95% CI, 1.3-6.2) and non-AIDS mortality (OR, 2.8; 95% CI, 1.5-5.3).


CONCLUSIONS
The CD4/CD8 ratio provides additional information to the CD4 counts and nadir CD4 in treated HIV-infected individuals, since it is independently associated with the risk of non-AIDS-related morbidity and mortality. This association is robust and maintained within different subgroups of patients.
Department of Infectious Diseases, Institute for Health Research (IRICYS), University Hospital Ramón y Cajal, Madrid, Spain.
Sergio
S
Serrano-Villar
Department of Infectious Diseases, Institute for Health Research (IRICYS), University Hospital Ramón y Cajal, Madrid, Spain.
María Jesús
MJ
Pérez-Elías
Department of Infectious Diseases, Institute for Health Research (IRICYS), University Hospital Ramón y Cajal, Madrid, Spain.
Fernando
F
Dronda
Department of Infectious Diseases, Institute for Health Research (IRICYS), University Hospital Ramón y Cajal, Madrid, Spain.
José Luis
JL
Casado
Department of Infectious Diseases, Institute for Health Research (IRICYS), University Hospital Ramón y Cajal, Madrid, Spain.
Ana
A
Moreno
CIBER, Epidemiología y Salud Pública, Clinical Biostatistics Unit, University Hospital Ramón y Cajal, IRYCIS, Madrid, Spain.
Ana
A
Royuela
Department of Infectious Diseases, Institute for Health Research (IRICYS), University Hospital Ramón y Cajal, Madrid, Spain.
José Antonio
JA
Pérez-Molina
Laboratory of Molecular Immune Biology, University Hospital Gregorio Marañón, Madrid, Spain.
Talia
T
Sainz
Department of Infectious Diseases, Institute for Health Research (IRICYS), University Hospital Ramón y Cajal, Madrid, Spain.
Enrique
E
Navas
Department of Infectious Diseases, Institute for Health Research (IRICYS), University Hospital Ramón y Cajal, Madrid, Spain.
José Manuel
JM
Hermida
Department of Infectious Diseases, Institute for Health Research (IRICYS), University Hospital Ramón y Cajal, Madrid, Spain.
Carmen
C
Quereda
Department of Infectious Diseases, Institute for Health Research (IRICYS), University Hospital Ramón y Cajal, Madrid, Spain.
Santiago
S
Moreno
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D002318:Cardiovascular Diseases / Q000276:immunology / Q000821:virology*; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000276:immunology / Q000821:virology*; D011446:Prospective Studies; D012372:ROC Curve; D012306:Risk
D019380:Anti-HIV Agents