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Can the CD4/CD8 Ratio Predict Risk of Co-Morbidities in HIV?

Elevated levels of certain inflammatory markers are associated with an increased risk of co-morbidities in HIV, but some markers are not widely available for clinical use. The ratio of CD4 to CD8 T-cells (CD4/CD8) is measured routinely in the clinical practice. Like many inflammatory markers, it is abnormal in most untreated patients, and improves but usually fails to normalize with virologically successful ART. Mussini et al [1] examined the occurrence of non-AIDS defining clinical events (nADEs) in 3236 patients enrolled in the ICONA study, who achieved viral suppression on ART and had a CD4/CD8 <1.0 at the time of suppression. This cohort was analyzed for improvement in CD4/CD8 over time and subsequent occurrence of nADEs. Reaching a CD4/CD8 >1.0 during follow-up was uncommon but was more likely with younger age, higher baseline CD4/CD8 and higher baseline CD4 count. In a multivariable model adjusted for age, gender, race, mode of HIV transmission, HCV co-infection, CDC C stage, and baseline HIV RNA and CD4 count, a current CD4/CD8 <0.3 was independently associated with an increased risk of nADEs or death (adjusted relative risk 1.64, p=0.002).

In another study examining CD4/CD8 in various populations of HIV-infected individuals on ART, Serrano-Villar et al [2] found higher levels of immune activation, immunosenescence markers and skewing of CD4 cells away from naive toward terminally differentiated phenotypes when the CD4/CD8 was <0.4 as compared to >1.0. They also reported significant negative correlations between CD4/CD8 and inflammatory markers including IL-6 and sCD14, which have previously been shown to correlate with mortality in HIV. Using case-control methodology, they found lower CD4/CD8 was an independent predictor of disease progression or death in two longitudinal cohorts of patients on ART. Comparing patients who initiated ART within 6 months of HIV infection or after 2 years of infection, they also found early ART initiators were more likely to achieve a CD4/CD8 >1.0 (OR 3.6, p=0.02). They concluded that a persistently low CD4/CD8 on ART, especially when the CD4 count is >500, may represent an important marker identifying increased risk of clinical disease events and death.

1. Mussini C, Lorenzini P, Cozzi-Lepri A, et al. Incidence of CD4/CD8 Ratio Normalization and Its Role in the Onset of Non-AIDS-Related Events. Abstract 753. CROI 2014, Boston, MA, March 3-6, 2014.
2. Serrano-Villar S, Sainz T, Lee SA, et al. A Low CD4/CD8 Ratio During Effective ART Predicts Immunosenescence and Morbidity/Mortality. Abstract 242. CROI 2014, Boston, MA, March 3-6, 2014.

Source: Reporting from Boston for PRN News: David H Shepp, MD