Imbalance in the game of T cells: What can the CD4/CD8 T-cell ratio tell us about HIV and health?

Antiretroviral treatment (ART) has transformed human immunodeficiency virus (HIV) from a deadly disease to a chronic illness that potentially has little effect on life expectancy. Modern ART can eliminate viremia and lower the risk of transmission. National data from the United States demonstrate that 81% of infected individuals receiving ART are virally suppressed [1]. With treatment available, HIV morbidity and mortality are not determined by opportunistic infections or AIDS-defining illnesses but rather by non-AIDS–defining conditions, including cardiovascular disease, liver disease, kidney disease, malignancies, neurocognitive disorders, and even autoimmune diseases [2]. To some, autoimmunity coexisting with HIV may be surprising; however, its presence illustrates how HIV’s immunopathology is more consistent with immune dysfunction than immune suppression alone. HIV viral load and the resulting decrease in absolute CD4 T cells have historically served as biomarkers for HIV’s immune suppression and response to treatment. However, with successful modern ART and viral suppression, absolute CD4 count and HIV viral load may not accurately reflect the risks facing patients because immune dysfunction persists despite normalization of CD4 counts [3]. One explanation is that these markers fail to truly describe HIV’s overall immune dysfunction contributing to today’s morbidity and mortality. The CD4/CD8 ratio more accurately describes this overall immune dysfunction and may be a better biomarker for disease progression, response to treatment, morbidity, and mortality for the virally suppressed. A greater understanding of the CD4/CD8 ratio and the impact of its manipulation should be a target for future HIV research.