Abstract
IntroductionAbsolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long-term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long-term treated patients.MethodWe conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV-positive patients in the context of treated infection.DiscussionLow CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called “inflammaging.” Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long-term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non-AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long-term treated HIV-positive adults.ConclusionThe CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long-term follow-up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune-based clinical trials.
Highlights
Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy
Historical perspective of the CD4:CD8 ratio as a prognostic factor for disease progression In 1989, Taylor et al compared the role of three immunological parameters in predicting disease progression to AIDS among 813 untreated HIV-seropositive men during a threeyear longitudinal study, i.e. absolute CD4 T cell count, CD4 T cell percentage and the CD4:CD8 ratio
Older patient age can be used as a predictor of clinical events, so do the additional markers such as neopterin, b2-microglobulin, soluble interleukin-2 receptors and immunoglobulin A (IgA)
Summary
Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Discussion: Low CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population This ratio may represent the combined effects of inflammation and immunological changes called ‘‘inflammaging.’’ the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long-term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non-AIDS morbidity and mortality. Antiretroviral therapy (ART) in a majority of patients suppresses HIV plasma viral load (VL) and stops the progression to AIDS, allowing progressive CD4 T cell recovery paired with a persistent elevation of CD8 T cells Such changes on T cell populations over time result in a partial restoration of the CD4:CD8 ratio. The reason for the persistence of elevated CD8 T cell counts during HIV infection was reviewed but has not been elucidated [5]
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