Predictive value of CD8+ T cell and CD4/CD8 ratio at two years of successful ART in the risk of AIDS and non-AIDS events

Serrano‐Villar, Sergio; Wu, Kun; Hunt, Peter W.; Lok, Judith J.; Ron, Raquel; Sainz, Talía; Moreno, Santiago; Deeks, Steven G.; Bosch, Ronald J.

doi:10.1016/j.ebiom.2022.104072

Cited by 12 publications

(29 citation statements)

References 50 publications

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“…In the Copenhagen cohort, a CD8 count >1500 cells/µL measured after ten years of ART predicted an 80% increased risk of non-AIDSassociated mortality compared to a lower CD8 count [19]. In the AIDS clinical trials group longitudinal linked randomized trials (ALLRT) cohort, a CD8 count >1500 cells/µL at year 2 of ART predicted a 75% increased risk of AIDS and non-infectious non-AIDS events during the following 5 years of treatment [14].…”

Section: Discussionmentioning

confidence: 99%

“…We explored different prognostic variables at baseline, including (i) reaching a CD4 count above 200, 350, and 500 cells/μL and (ii) reaching a CD4/CD8 ratio above the cut-off values of 0.2, 0.3, 0.4, and 0.5. These thresholds were selected before analysis and were based on previous studies [8,9,[12][13][14]. Furthermore, we assessed the ability of CD8+ count (at 800, 1000, and 1500 cells/μL cut-offs) [14,19] and CD4/CD8 ratio to predict the outcome in the subpopulation of participants with a CD4+ count > 500 cells/μL at year two.…”

Section: Prognostic Variables Follow-up and Outcomesmentioning

confidence: 99%

“…These thresholds were selected before analysis and were based on previous studies [8,9,[12][13][14]. Furthermore, we assessed the ability of CD8+ count (at 800, 1000, and 1500 cells/μL cut-offs) [14,19] and CD4/CD8 ratio to predict the outcome in the subpopulation of participants with a CD4+ count > 500 cells/μL at year two.…”

Section: Prognostic Variables Follow-up and Outcomesmentioning

confidence: 99%

“…However, results are conflicting, with variations in study designs, timing of ratio measurement, ratio thresholds, and endpoints. While some studies have found a significant association between a low CD4/CD8 ratio and an increased risk of SNAEs or mortality [7][8][9][10][11][12], others have failed to find this association [14,15]. This lack of consensus has led to discrepancies in clinical guidelines regarding the appropriateness of monitoring the CD4/CD8 ratio [16,17].…”

Section: Introductionmentioning

confidence: 99%

“…Most evidence linking this marker to clinical outcomes has been generated in retrospective cohort studies, which may be limited by the lack of data on CD8 count, high rates of loss to follow-up, and inability to adjudicate clinical events [8,9,13,15,18]. The most informative cut-off values are still unclear, as are the type of events that these markers can predict, and the timing of the measurement relative to ART initiation [8,9,[12][13][14]19]. Furthermore, extracting the independent impact of CD8 count is difficult, as their increase may be a homeostatic response to a low CD4 count [19].…”

Section: Introductionmentioning

confidence: 99%

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Expanding HIV Clinical Monitoring: The Role of CD4, CD8, and CD4/CD8 Ratio in Predicting Non-AIDS Events

Martínez‐Sanz

Álvarez

Rosas

et al. 2023

Preprint

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Background While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Results The study included 4625 participants, of whom 4.3% experienced an SNAE during the follow-up period. A CD4/CD8 ratio <0.3 predicted an increased risk of SNAEs during the next five years (OR 1.63, 95%CI 1.03-2.58). The effect was stronger at a CD4/CD8 ratio cut-off of <0.2 (OR 3.09, 95%CI 1.57-6.07). Additionally, low CD4 count at cut-offs of <500 cells/μL predicted an increased risk of clinical events. Among participants with a CD4 count ≥500 cells/μL, a CD8 count ≥1500 cells/μL or a CD4/CD8 ratio <0.4 predicted increased SNAE risk. Conclusions Our results support the use of the CD4/CD8 ratio and CD8 count as predictors of clinical progression. Patients with CD4/CD8 ratio <0.3 or CD8 count ≥1500/μL, regardless of their CD4 count, may benefit from closer monitoring and targeted preventive interventions.

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Section: Discussionmentioning

confidence: 99%

Section: Prognostic Variables Follow-up and Outcomesmentioning

confidence: 99%

Section: Prognostic Variables Follow-up and Outcomesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Expanding HIV Clinical Monitoring: The Role of CD4, CD8, and CD4/CD8 Ratio in Predicting Non-AIDS Events

Martínez‐Sanz

Álvarez

Rosas

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS events

Díaz-Álvarez¹,

Rosas²,

Ron³

et al. 2023

eBioMedicine

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CD4/CD8 Ratio During Human Immunodeficiency Virus Treatment: Time for Routine Monitoring?

Ron

Moreno

Martínez‐Sanz

et al. 2023

Clinical Infectious Diseases

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In the last decade, studies in PWH on ART have shed light on the significance of persistently high CD8 counts and low CD4/CD8 ratios. A low CD4/CD8 ratio translates increased immune activation and is associated with an increased risk of severe non-AIDS events. As a result, many clinicians now believe that the CD4/CD8 ratio can help in HIV monitoring, and many researchers now report it as an efficacy marker in interventional studies. However, the topic is more complex. Recent studies have not yielded unanimous conclusions on the ability of CD4/CD8 ratio to predict adverse outcomes, and only some clinical guidelines recommend monitoring it. Knowledge gaps remain on the best cut-off points, associated clinical events, effects of treatments, and how CD4/CD8 ratio could improve decision-making in the clinic. Here, we critically review the literature, identify knowledge gaps and discuss the role of the CD4/CD8 ratio as a marker for HIV monitoring.

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Predictive value of CD8+ T cell and CD4/CD8 ratio at two years of successful ART in the risk of AIDS and non-AIDS events

Cited by 12 publications

References 50 publications

Expanding HIV Clinical Monitoring: The Role of CD4, CD8, and CD4/CD8 Ratio in Predicting Non-AIDS Events

Expanding HIV Clinical Monitoring: The Role of CD4, CD8, and CD4/CD8 Ratio in Predicting Non-AIDS Events

Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS events

CD4/CD8 Ratio During Human Immunodeficiency Virus Treatment: Time for Routine Monitoring?

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