CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV‐positive patients

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.

A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV

“…[23] The CD4/CD8 ratio falls dramatically in early HIV infection, reflecting a decline in CD4 count and a proliferation of HIV-specific CD8+ T-cells. With effective ART, most patients experience a reconstitution of CD4+ T-cells and many have a decline in the CD8+ T-cells with a normalized ratio.…”

CD4/CD8 Ratio Predicts Peripheral Fat in HIV-Infected Population

“…10,11 This increase in chronic inflammation has been hypothesized to explain the association between low CD4/CD8 ratio and non-AIDS related complications, such as cardiovascular disease, end-staged kidney disease, and non-AIDS malignancies. 12,13 Very low CD4/CD8 ratios (< 0.3) independently predict the risk of serious non-AIDS events or deaths including cardio-metabolic disease. 14 Our data suggests that low CD4/CD8 ratios are also a predictor of decreased subcutaneous fat loss.…”

Very early antiretroviral therapy permits CD8 T cells to keep HIV reservoirs at bay

“…Indeed, only early initiation rather than prolonged duration of ART contributes to the normalization of CD8 T cell counts (2,5). These observations in treated HIV infection have led to consider the CD4/CD8 ratio as a better marker than CD4 or CD8 T cell counts in predicting risk of inflammatory non-AIDS events, level of immune exhaustion and HIV reservoir size (6).…”