A study of 2006 people on antiretroviral therapy (ART) linked a higher (better) CD4/CD8 ratio to a lower risk of coronary artery disease (CAD) after one year of viral suppression. Men had lower CD4/CD8 ratios than women in this prospective single-center study.
Noncommunicable (non-AIDS) diseases (NCDs) are a growing concern in the aging population with HIV infection. The immunologic impact of HIV infection may be one mechanism contributing to NCDs in people with HIV. In particular, previous research a lower CD4/CD8 ratio to NCDs in HIV-positive people. Vanderbilt University researchers and colleagues conducted this study to explore the impact of age on the relationship between CD4/CD8 ratio and NCD incidence.
The study included HIV-positive adults who began or continued ART during the period from January 1998 to December 2012 at the Vanderbilt HIV clinic. Follow-up began when a person maintained a viral load below 400 copies/mL through 12 months of ART. From that baseline, the researchers recorded serious NCDs defined as cardiovascular disease (including coronary artery disease [CAD]), non-AIDS cancers, cirrhosis, advanced chronic kidney disease and diabetes. The primary predictor of interest was a CD4/CD8 ratio after 12 months of viral suppression categorized as low (<0.40), middle (0.40 to 0.69) or high (≥0.70). The Vanderbilt team used linear regression analysis to explore the association between age and change in CD4/CD8 ratio after three years of viral suppression. It used Cox proportional hazards models to assess the impact of CD4/CD8 ratio on NCD incidence.
The 2006 study participants had a median baseline CD4/CD8 ratio of 0.57 and included 610 (30%) with a low ratio, 650 (32%) with a middle ratio and 746 (37%) with a high ratio. Respective median ages were 44, 41 and 40 years (P < .001) and proportions of men 85%, 77% and 72% (P < .001). About 43% of participants were nonwhite, with no significant racial difference between CD4/CD8 groups. Among 530 participants with viral suppression sustained for three years, CD4/CD8 ratio rose over time by a median of 0.17.
Among all 2006 participants, 182 NCDs developed including 69 cases of cardiovascular disease, 46 of which were CAD. Median baseline CD4/CD8 ratio was 0.58 for people with no incident NCD, 0.42 for people with incident cardiovascular disease and 0.37 for people with incident CAD.
CD4/CD8 ratio was inversely associated with risk of any NCD (the higher the ratio, the lower the NCD risk) in an unadjusted analysis, but not in an analysis adjusted for age, sex, CD4 count and other variables. In the same way, higher CD4/CD8 ratio predicted lower risk of cardiovascular disease in an unadjusted analysis but not in the adjusted analysis. The association between CD4/CD8 ratio and NCD risk retained significance in the adjusted model only for CAD: Every 0.1 higher CD4/CD8 ratio lowered CAD risk 13% (adjusted hazard ratio [aHR] 0.87, 95% confidence interval [CI] 0.76 to 0.99, P = .034). That association between higher CD4/CD8 ratio and lower CAD risk held true for patients younger than 50 years old (aHR 0.83, 95% CI 0.70 to 0.97, P = .019) but not for older patients, though this analysis was limited by the small number of older patients with incident CAD.
Cox proportional hazard models also identified an association between history of depression and any NCD (aHR 1.66, 95% CI 1.22 to 2.27, P = .001), cardiovascular disease (aHR 2.35, 95% CI 1.44 to 3.85, P = .001), CAD (aHR 1.69, 95% CI 0.93 to 3.10, P = .088) and diabetes (aHR 1.98, 95% CI 1.11 to 3.54, P = .021) after adjustment for relevant variables.
The researchers conclude that, in adults on stable ART, the CD4/CD8 ratio is "an important measure of aging-associated immune senescence and a significant, independent predictor of CAD events."