Determinants of a Low CD4/CD8 Ratio in HIV-1–Infected Individuals Despite Long-term Viral Suppression

Caby, Fabienne; Guihot, Amélie; Lambert-Niclot, Sidonie; Guiguet, Marguerite; Boutolleau, David; Agher, Rachid; Valantin, Marc‐Antoine; Tubiana, Roland; Cálvez, Vincent; Marcelin, Anne–Geneviève; Carcelain, Guislaine; Autran, Brigitte; Costagliola, Dominique; Katlama, Christine

doi:10.1093/cid/ciw076

Cited by 66 publications

(55 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the Italian cohort ICONA, the proportion of normalisation of CD4/CD8 ratio above 1 was 29.4% at 5 years of follow-up and an additional factor found associated with higher ratio was the lack of co-infection with cytomegalovirus (CMV) [17], a data that was not available in our cohort. Co-infection with CMV was also a determinant of a lower probability to reach a CD4/CD8 ratio above 1 in a transversal study conducted in Paris [18]. The mechanisms underlying the slow recovery of CD4/CD8 ratio despite the effectiveness of cART remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Low CD4/CD8 Ratio Is Associated with Non AIDS-Defining Cancers in Patients on Antiretroviral Therapy: ANRS CO8 (Aproco/Copilote) Prospective Cohort Study

et al. 2016

View full text Add to dashboard Cite

ObjectivesTo study the association between CD4/CD8 ratio and morbidity in HIV-infected patients on antiretroviral therapy (ART).MethodsThe APROCO/COPILOTE cohort enrolled patients initiating a protease inhibitor-containing ART in 1997–1999. The association between occurrence of first non AIDS-defining severe events (NADE) and time-dependent measures of immune restoration was assessed by 4 Cox models with different definitions of restoration, CD4+ cell counts (CD4), CD4/CD8 ratio, both CD4 and CD4/CD8 ratio, or a composite variable (CD4< 500/mm3, CD4 > 500/mm3 and CD4/CD8 ratio < 1, CD4 > 500/mm3 and CD4/CD8 ratio > 1). Models adjusted on baseline characteristics and time-dependent viral load were compared using Akaike Information Criterion.ResultsWe included 1227 patients. Median duration of follow-up was 9.2 years (IQR: 4.2–11.4). Median CD4 was 530/mm3 at 9 years. Median CD4/CD8 ratio was 0.3 (IQR: 0.2–0.5) at baseline and 0.6 (IQR: 0.4–0.9) after 9 years. Incidence of first NADE was 7.4/100 person-years, the most common being bacterial infections (21%), cardiovascular events (14%) and cancers (10%). For both bacterial infections and cardiovascular events, the CD4/CD8 ratio did not add predictive information to the CD4 cell count. However, low CD4/CD8 ratio was the best predictor of non-AIDS cancers (adjusted HR = 2.13 for CD4/CD8 < 0.5; 95% CI = 1.32–3.44).ConclusionsCD4/CD8 ratio remains < 1 in most HIV-infected patients despite long-term CD4+ cell counts restoration on ART. A CD4/CD8 ratio < 0.5 could identify patients who require a more intensive strategy of cancer prevention or screening.

show abstract

Section: Discussionmentioning

confidence: 99%

Low CD4/CD8 Ratio Is Associated with Non AIDS-Defining Cancers in Patients on Antiretroviral Therapy: ANRS CO8 (Aproco/Copilote) Prospective Cohort Study

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Even in the setting of normal CD4 + counts among treated HIV-infected persons, low CD4/CD8 is associated with poor clinical outcomes [5,6], T-cell dysfunction [6][7][8], and increased inflammation (eg, interleukin 6, C-reactive protein, soluble CD14) [6,9]. These data suggest that CD8 + T-cell expansion might be a driver of increased morbidity and mortality [6,10].…”

mentioning

confidence: 99%

“…These bursts of replication are linked to persistent stimulation of the CD8 + T-cell population [13,14]. Along these lines, positive CMV serology among persons with chronic HIV infection is associated with lower CD4/CD8 ratio during ART [7]. A recent study found elevated CD8 + T cells and low CD4/CD8 only in individuals coinfected with both viruses, but not in persons infected with HIV or CMV alone [13].…”

mentioning

confidence: 99%

Asymptomatic CMV Replication During Early Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower CD4/CD8 Ratio During HIV Treatment

et al. 2016

View full text Add to dashboard Cite

Background. A low CD4/CD8 ratio in human immunodeficiency virus (HIV)-infected individuals is associated with inflammation and higher risk of non-AIDS morbidity and mortality. In this study, we investigated the effect of subclinical cytomegalovirus (CMV) and Epstein-Barr virus (EBV) replication on CD4 + and CD8 + T-cell dynamics when antiretroviral therapy (ART) is started during early infection.Methods. We investigated 604 peripheral blood mononuclear cell samples from 108 CMV-and EBV-seropositive HIV-infected men who have sex with men, who started ART within a median of 4 months from their estimated date of infection and were followed for a median of 29.1 months thereafter. Levels of CMV and EBV DNA were measured at each timepoint. Mixed-effects asymptotic regression models were applied to characterize CD4 + and CD8 + T-cell dynamics, and Bayesian hierarchical models were used to quantify individual differences in CMV and EBV DNA replication.Results. Higher levels of subclinical CMV replication were associated with lower predicted maximum levels of CD4/CD8 ratio (P < .05), which was driven by higher levels of CD8 + T-cell counts (P < .05), without affecting CD4 + T-cell counts (P > .1). Age was negatively associated with CD4/CD8 levels (P < .05), and this effect was independent of the CMV association (P < .05 for both CMV and age in a multivariate model).Conclusions. Subclinical CMV replication in blood cells during early HIV infection and younger age were associated with lower CD4/CD8 ratios during suppressive ART. These findings suggest that active CMV infection in the setting of treated HIV may represent an attractive potential target for therapeutic intervention.

show abstract

“…Our study has some limitations. First, we did not analyse variables related to reduced immunological recovery such as cytomegalovirus serology [5,34], but the double blind design of the study limits any bias in this sense. Second, this is a post-hoc analysis.…”

Section: Discussionmentioning

confidence: 99%

Immune recovery markers in a double blind clinical trial comparing dolutegravir and raltegravir based regimens as initial therapy (SPRING-2)

2020

View full text Add to dashboard Cite

BackgroundMultiple T-cell marker recovery (MTMR: CD4+ T-cells >500 cel/mm 3 plus CD4+% >29% plus CD4+/CD8+ ratio >1) has been proposed as the most complete level of immune reconstitution. In this study we quantified differences in the CD4+/CD8+ ratio, CD4+% recovery and MTMR after starting HIV-1 treatment with dolutegravir (DTG) vs. raltegravir (RAL) plus a NRTI backbone. MethodsExploratory post-hoc analysis of the SPRING-2 study, a randomized double-blind clinical trial comparing DTG and RAL as third agents in naive HIV-infected patients at 100 sites in Canada, USA, Australia, and Europe. Percentage differences and corresponding precision based on 95% confidence intervals (CI) and p-values were calculated for i) CD4+/CD8+ ratio normalization, ii) CD4+% normalization, and iii) the achievement of MTMR. ResultsA total of 822 participants were analyzed (411 in each group). No statistically significant differences in the proportion of patients who reached a CD4+/CD8+ ratio �0.5 & �1 at w48 & w96 were observed. At w96, the proportion of patients with a CD4+/CD8+ ratio �1 was similar (30.43% DTG vs. 29.57% RAL). No differences were observed in the mean increase in CD4+/CD8+ ratio from baseline at both w48 & w96. Similarly, no significant differences in the CD4+/CD8+>29% were observed at w96 (72.95% DTG vs 69.28% RAL). The proportion of patients attaining MTMR criteria was also similar in the DTG group and the RAL group at w48 (20.33% vs. 18.26%; difference 2.07 (95%CI (-3.67;7.81) P = 0.481 and w96 (28.70% vs. 27.13; difference 1.56 (95%CI -5.22;8.34) P = 0.652).

show abstract

Determinants of a Low CD4/CD8 Ratio in HIV-1–Infected Individuals Despite Long-term Viral Suppression

Cited by 66 publications

References 39 publications

Low CD4/CD8 Ratio Is Associated with Non AIDS-Defining Cancers in Patients on Antiretroviral Therapy: ANRS CO8 (Aproco/Copilote) Prospective Cohort Study

Low CD4/CD8 Ratio Is Associated with Non AIDS-Defining Cancers in Patients on Antiretroviral Therapy: ANRS CO8 (Aproco/Copilote) Prospective Cohort Study

Asymptomatic CMV Replication During Early Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower CD4/CD8 Ratio During HIV Treatment

Immune recovery markers in a double blind clinical trial comparing dolutegravir and raltegravir based regimens as initial therapy (SPRING-2)

Contact Info

Product

Resources

About