Table 1.
CD4+ T cell counts, CD8+ T cell counts and CD4/CD8 ratio correlations with the percentage of T cell maturation subsets and T cell activation phenotypes in HIV-infected participants in SCOPE cohort.
Figure 1.
Percentages and absolute counts of CD8+ T cell maturation subsets among HIV-/CMV+ individuals and ART-suppressed HIV-infected patients with CD4 counts >500 cells/mm3 stratified by a normal (4th quartile, ≥1) or low (1st quartile, ≤0.4) CD4/CD8 ratio.
HIV-infected individuals with low CD4/CD8 ratio had lower percentages of TN, TCM, and TTR CD8+ cells, higher TEM and TEMRA (A), and higher absolute counts (B) of all subsets compared to those with higher CD4/CD8 ratio and with healthy controls.
Figure 2.
Percentages and absolute counts of CD8+ activation phenotypes among HIV-/CMV+ individuals and ART-suppressed HIV-infected patients with CD4 counts >500 cells/mm3 stratified by a normal (4th quartile, ≥1, in green) or low (1st quartile, ≤0.4, in red) CD4/CD8 ratio.
Subjects with low CD4/CD8 ratio showed higher percentages (A) and absolute counts (B) of HLADR+, CD28− and CD28−CD57+, and higher absolute counts of PD1+ cells (B). There were no differences in HIV-infected individuals in the proportion of CD28−CD8+ T cells expressing CD57, being significantly lower in both groups compared to HIV-/CMV+ controls.
Table 2.
Correlations with biomarkers of T cell activation and senescence in SOCA cohort.
Figure 3.
Association between the CD4/CD8 ratio and the % of CD28−CD8+ T cells with indoleamine 2,3-dioxygenase-1 (IDO-1) activity (kinurenine/tryptophan ratio) among participants in the SOCA cohort with 500 CD4+ T cells/mm3.
The KT ratio significantly correlated with the CD4/CD8 ratio and the % of CD28+CD8+ T cells. The between the CD4/CD8 ratio and the KT ratio was confirmed in a linear regression analysis adjusted by age, gender and cumulative ART exposure (Beta = −0.72, P = 0.009). The red line represents a linear prediction.
Table 3.
Correlations with biomarkers of innate immune activation and epithelial integrity in SOCA cohort.
Table 4.
Multivariate linear regression analysis: Associations of the KT ratio (dependent variable) with CD4+ and CD8+ T cells, and the CD4/CD8 ratio (independent variables) in SOCA cohort.
Figure 4.
Association between the CD4/CD8 ratio in blood and in lymph nodes or in GALT.
While no association with the CD4/CD8 ratio in lymph nodes was detected (A), it correlated positively with the ratio in GALT (B). The red line represents a linear prediction.
Figure 5.
Impact of early or later ART initiation in peripheral CD4+ T cell counts, CD8+ T cell counts and CD4/CD8 ratio in the OPTIONS cohort.
The CD4/CD8 ratio was compared between HIV-uninfected individuals (blue) and HIV-infected individuals initiating ART “early,” ≤6 months of infection (green), or “later,” ≥2 years after initial infection (red), at acute HIV diagnosis and after 1 year of ART. Median CD4/CD8 ratio was significantly higher after one year in early ART initiators compared to later initiators. (A). Early ART initiators experienced higher CD4+ T cell increase (B) than later initiators (C) after one year of ART (221 cells/mm3 vs. 130, respectively, P<0.001). No differences were observed in CD8+ T cell counts between early (D) and later ART initiators (E) after one year of ART (−212 cells/mm3 vs. −114, respectively, P = 0.098) but CD8+ T cells were significantly different between groups beyond one year of ART (−309 cells/mm3 vs. −114, respectively, P = 0.014). Changes in the CD4/CD8 ratio among recently HIV-infected individuals initiating ART early (F) and later (G) were also assessed over time. Early ART initiators experienced a higher increase at one year of ART than later initiators (+0.43 vs. +0.25, P<0.001). Individual participant trajectories shown with red lines, estimated mean values over time from linear mixed models adjusted by age, sex, baseline CD4+ T cells shown in thick black lines.
Table 5.
Conditional logistic regression analysis: Predicted morbidity and mortality by the CD4+ and CD8+ T cell counts and the CD4/CD8 ratio in the Madrid cohort and SOCA cohort mortality nested studies.