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. 2014 Jan 30;9(1):e85798.
doi: 10.1371/journal.pone.0085798. eCollection 2014.

Increased risk of serious non-AIDS-related events in HIV-infected subjects on antiretroviral therapy associated with a low CD4/CD8 ratio

Sergio Serrano-Villar  1 , María Jesús Pérez-Elías  1 , Fernando Dronda  1 , José Luis Casado  1 , Ana Moreno  1 , Ana Royuela  2 , José Antonio Pérez-Molina  1 , Talia Sainz  3 , Enrique Navas  1 , José Manuel Hermida  1 , Carmen Quereda  1 , Santiago Moreno  1
Affiliations

Increased risk of serious non-AIDS-related events in HIV-infected subjects on antiretroviral therapy associated with a low CD4/CD8 ratio

Sergio Serrano-Villar et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Selection of study participants.
Figure 2
Figure 2. CD4/CD8 ratio according to the presence and type of event.
The CD4/CD8 in controls [0.70 (IQR 0.48–0.94)] was significantly higher than in subjects who developed non-AIDS events [0.46 (IQR 0.31–0.68), P<0.0001], including non-AIDS defining malignancies (N = 35) [0.44 (IQR 0.25–0.71), P = 0.0001], Hodgkin lymphoma (N = 10) [0.41 (IQR 0.33–0.57), P = 0.0039], ischemic heart disease (N = 38) [0.47 (IQR 0.32–0.63), P = 0.0001], stroke (N = 15) (0.46 [IQR 0.28–0.83), P = 0.013), and end-stage kidney disease (N = 9) [0.33 (0.32–0.53), P = 0.028]. The CD4/CD8 ratio was also significantly lower in subjects with non-AIDS associated mortality (N = 29) [0.33 (IQR 0.22–0.46), P<0.0001].
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