Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 Feb 1:15:1343124.
doi: 10.3389/fimmu.2024.1343124. eCollection 2024.

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

Raquel Ron  1   2 , Javier Martínez-Sanz  1   2 , Sabina Herrera  3 , Luis Ramos-Ruperto  4 , Alejandro Díez  4 , Talía Sainz  5 , Noelia Álvarez-Díaz  6 , Andrea Correa-Pérez  7   8   9 , Alfonso Muriel  9 , Jesús López-Alcalde  7   9   10 , José A Pérez-Molina  1   2 , Santiago Moreno  1   2 , Sergio Serrano-Villar  1   2
Affiliations
Meta-Analysis

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

Raquel Ron et al. Front Immunol. .

Erratum in

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.

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

Findings: We identified 2,479 studies for screening. 20 studies were included in the systematic review. Seven studies found an association between low CD4/CD8 ratio categories and increased mortality risk, with variable cut-off points between 0.4-1. Four studies were selected for meta-analysis, including 12,893 participants and 618 reported deaths. Patients with values of CD4/CD8 ratio below 0.5 showed a higher 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 methodological differences between studies, the systematic review suggests a negative prognostic impact of higher values (>1,138 to 1,500 cells/uL) in the long term.

Conclusions: 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.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020170931, identifier CRD42020170931.

Keywords: CD4/CD8 ratio; HIV; comorbidities; mortality; non-AIDS events.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Studies selection flowcharts showing identification, screening, inclusion and exclusion process.
Figure 2
Figure 2
Estimated effect of CD4 /CD8 ratio on the risk on non-AIDS mortality or all-cause mortality. Random effect of meta-analysis comparing low vs. high CD4/CD8 ratios. (OR, Odds Ratio). Events include the total number of deaths reported.
Figure 3
Figure 3
Estimated effect of CD4/CD8 ratio on the risk of clinical events or mortality. Random effects meta-analysis by association measurement (HR, Hazard Ratio/OR, Odss Ratio) comparing low vs. high CD4/CD8 ratios. 1 composite including AIDS, non-AIDS events, and all-cause mortality. 2 composite outcomes including non-AIDS events and non-AIDS mortality.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Antiretroviral Therapy Cohort Collaboration . Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet (2008) 372(9635):293–9. doi: 10.1016/S0140-6736(08)61113-7 - DOI - PMC - PubMed
    1. May MT, Gompels M, Delpech V, Porter K, Orkin C, Kegg S, et al. . Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS (2014) 28(8):1193–202. doi: 10.1097QAD.0000000000000243 - PMC - PubMed
    1. Serrão R, Piñero C, Velez J, Coutinho D, Maltez F, Lino S, et al. . Non-AIDS-related comorbidities in people living with HIV-1 aged 50 years and older: The AGING POSITIVE study. Int J Infect Dis (2019) 79:94–100. doi: 10.1016/j.ijid.2018.10.011 - DOI - PubMed
    1. Collins LF, Sheth AN, Mehta CC, Naggie S, Golub ET, Anastos K, et al. . The prevalence and burden of non-AIDS comorbidities among women living with or at risk for human immunodeficiency virus infection in the United States. Clin Infect Dis (2021) 72(8):1301–11. doi: 10.1093/cid/ciaa204 - DOI - PMC - PubMed
    1. Pelchen-Matthews A, Ryom L, Borges ÁH, Edwards S, Duvivier C, Stephan C, et al. . Aging and the evolution of comorbidities among HIV-positive individuals in a European cohort. AIDS (2018) 32(16):2405–16. doi: 10.1097/QAD.0000000000001967 - DOI - PubMed