CD4/CD8 Ratio and CD8 T-Cell Count as Prognostic Markers for Non-Aids Mortality in People Living with HIV. A Systematic Review and Meta-Analysis

Abstract

Background: In people living with HIV (PLHIV), the CD4/CD8 ratio has been proposed as a useful marker for non-AIDS events. However, its predictive ability on mortality over CD4 counts, and the role of CD8+ T-cell counts remain controversial. We aim to evaluate CD4/CD8 ratio and CD8+ counts as prognostic markers for mortality in PLHIV and adequate virological control.

Methods: We conducted a systematic review and meta-analysis of published studies from 1996 to 2023, including PLHIV on antiretroviral treatment, reporting CD4/CD8 ratio or CD8+ counts, and non-AIDS or all-cause mortality. The summary extracted and additional requested data were reviewed. The primary outcome was non-AIDS mortality or all-cause mortality. We performed a standard random-effects pairwise meta-analysis model comparing low versus high CD4/CD8 ratio with a predefined cut-off point of 0.5 (PROSPERO CRD42020170931).

Findings: We identified 2,479 studies for screening. We included 20 studies in the systematic review, with 184,402 participants and 6,940 reported deaths. 19 studies evaluated the CD4/CD8 ratio, and six studies assessed CD8+ T-cell counts. Seven studies found an association between low CD4/CD8 ratio categories and increased mortality risk, with variable cut-off points ranging between 0.4-1. Four studies were selected for meta-analysis due to methodologic differences and high heterogeneity, including 12,893 participants and 618 reported deaths. Patients with values of CD4/CD8 ratio below 0.5 showed a higher estimated mortality risk (OR 3·65; 95% CI 3·04 - 4·35; I2=0·00%) compared to those with higher values. While the meta-analysis of CD8+ T-cell counts was not feasible due to differences between studies, the systematic review suggests a negative prognostic impact of persistent higher values (>1,138 to 1,500 cells/uL) in the long term.

Interpretation: Our results support the use of the CD4/CD8 ratio as a prognostic marker in clinical practice, especially in patients with values below 0·5, but consensus criteria on ratio timing measurement, cut-off values, and time to event are needed in future studies to get more robust conclusions.

Funding: None.

Declaration of Interest: Declare no conflict of interest directly related to this work.

Keywords: HIV, CD4/CD8 ratio, CD8+ counts, mortality, non-AIDS events