ObjectivesInversion of the CD4:CD8 ratio (< 1) has been identified as a hallmark of inmmunosenescence and an independent predictor of mortality in the general population. We aimed to assess the association between the CD4:CD8 ratio and markers of age-associated disease in treated HIV-infected patients with good immunovirological response.
MethodsA cross-sectional analysis was conducted in 132 HIV-infected adults on antiretroviral therapy (ART), with plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 1 year, CD4 count > 350 cells/μL and age < 65 years. We analysed the associations between the CD4:CD8 ratio and subclinical atherosclerosis [assessed using carotid intima-media thickness (IMT)], arterial stiffness [assessed using the augmentation index (AIx)], the estimated glomerular filtration rate (eGFR), muscle wasting and sarcopenia [assessed using appendicular lean mass/height 2 (ALM) measured by dual-energy X-ray absorptiometry (DEXA)].
Results
CD4:CD8 ratio inversion was associated with higher IMT, lower eGFR and lower ALM (all values P < 0.05), but not with AIx. In multivariate analyses adjusted for age, sex, hypertriglyceridaemia, tobacco use and cumulative ART exposure, inversion of the CD4:CD8 ratio was independently associated with higher IMT [odds ratio (OR) 2.9; 95% confidence interval (CI) 1.2-7.1], arterial stiffness (OR 4.8; 95% CI 1.0-23.5) and lower eGFR (OR 5.2; 95% CI 1.0-64.4), but not sarcopenia (OR 0.7; 95% CI 0.2-2.7). These associations persisted when models were applied to subjects with nadir CD4 counts > 200 cells/μL and those with CD4 counts > 500 cells/μL.
ConclusionsThe CD4:CD8 ratio in treated HIV-infected subjects with good immunovirological response is independently associated with markers of age-associated disease. Hence, it might be a clinically useful predictor of non-AIDS-defining conditions. Keywords: carotid intima-media thickness, CD4:CD8 ratio, HIV, premature aging, sarcopenia, vascular stiffness
Accepted 24 July 2013
IntroductionAntiretroviral therapy (ART) is among the greatest successes of modern medicine, having rapidly changed the prognosis of HIV-infected individuals from years to decades of survival. However, ART has failed in its attempt to completely restore normal health to HIV-infected subjects. Although the reasons remain poorly understood, subjects on successful ART still present increased morbidity and mortality relative to uninfected individuals [1][2][3]. This shortening of the expected life span has recently been associated with increased risk of so-called 'non-AIDSrelated' complications, which include cardiovascular disease, renal impairment, liver disease, neurocognitive disorders, non-AIDS-defining cancers, osteoporosis, muscle wasting and frailty. All these complications are generally associated with aging, and concern has been increasing regarding the possibility that persons living with HIV suffer from an 'accelerated aging' syndrome [4]. Most of these noninfectious conditions have been related to the ongoing immune activation and low-level systemic ...