Higher CD27+CD8+ T cells percentages during suppressive antiretroviral therapy predict greater subsequent CD4+ T cell recovery in treated HIV infection (original) (raw)
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Background-While persistent T-cell activation has been cross-sectionally associated with poor CD4+ T-cell restoration in HIV-infected individuals maintaining antiretroviral treatment (ART)mediated viral suppression, it remains unclear whether CD8+ T-cell activation is of predictive effect on CD4+ T-cell recovery. Objective-We assessed whether the extent of persistent CD8+ T-cell activation (% CD38+/ HLA-DR+) in the fi rst few years of ART-mediated viral suppression predicted subsequent CD4+ T-cell recovery in 95 subjects with up to 15 years of observation on suppressive ART. Results-Lower CD8+ T-cell activation and higher naïve CD4+ T-cell frequencies (CD45RA+/ CD62L+) measured at year 3 to 5 after starting ART independently predicted greater subsequent CD4+ T-cell increases. The mean CD4 count increase from year 0 to year 5 and the increase to the average of year 10 to 15 in the low CD8 activation group (≤18.5%; mean = 13%) were 342 and 458 cells/mm, 3 and the increases were 248 and 349 cells/mm 3 for the high CD8 activation group (>18.5%; mean = 29%) (P = .002 and P = .016, respectively, comparing groups). At years 10 to 15, the mean CD4 counts in the groups were 579 and 484 cells/mm 3 , respectively (P = .026). Conclusion-These fi ndings support the need to identify approaches to reduce immune activation in treated HIV disease.
The Journal of Infectious Diseases, 2006
Background. Suboptimal CD4 + T cell recovery during antiretroviral therapy (ART) is a common clinical dilemma. Methods. We analyzed viral and immunologic predictors of CD4 + T cell recovery in 116 human immunodeficiency virus type 1 (HIV-1)-infected subjects who had suppressed viremia (р50 copies/mL) while receiving ART. Successive measurements of T cell immunophenotypes and cellular HIV-1 DNA levels were obtained before and during receipt of ART. On the basis of increases in the CD4 + T cell count, subjects were classified as immunologically concordant (demonstrating an increase of у100 CD4 + T cells/mm 3 ) or discordant (demonstrating an increase of !100 CD4 + T cells/mm 3 ) after 48 weeks of ART.
Clinical Infectious Diseases, 2005
Background. The CD4 T cell count recovery in human immunodeficiency virus type 1 (HIV-1)-infected individuals receiving potent antiretroviral therapy (ART) shows high variability. We studied the determinants and the clinical relevance of incomplete CD4 T cell restoration. Methods. Longitudinal CD4 T cell count was analyzed in 293 participants of the Swiss HIV Cohort Study who had had a plasma HIV-1 RNA load !1000 copies/mL for у5 years. CD4 T cell recovery was stratified by CD4 T cell count 5 years after initiation of ART (у500 cells/mL was defined as a complete response, and !500 cells/mL was defined as an incomplete response). Determinants of incomplete responses and clinical events were evaluated using logistic regression and survival analyses. Results. The median CD4 T cell count increased from 180 cells/mL at baseline to 576 cells/mL 5 years after ART initiation. A total of 35.8% of patients were incomplete responders, of whom 47.6% reached a CD4 T cell plateau !500 cells/mL. Centers for Disease Control and Prevention HIV-1 disease category B and/or C events occurred in 21% of incomplete responders and in 14.4% of complete responders (). Older age (adjusted P 1 .05 odds ratio [aOR], 1.71 per 10-year increase; 95% confidence interval [CI], 1.21-2.43), lower baseline CD4 T cell count (aOR, 0.37 per 100-cell increase; 95% CI, 0.28-0.49), and longer duration of HIV infection (aOR, 2.39 per 10-year increase; 95% CI, 1.19-4.81) were significantly associated with a CD4 T cell count !500 cells/mL at 5 years. The median increases in CD4 T cell count after 3-6 months of ART were smaller in incomplete responders () and predicted, in conjunction with baseline CD4 T cell count and age, incomplete response with 80% P ! .001 sensitivity and 72% specificity. Conclusion. Individuals with incomplete CD4 T cell recovery to !500 cells/mL had more advanced HIV-1 infection at baseline. CD4 T cell changes during the first 3-6 months of ART already reflect the capacity of the immune system to replenish depleted CD4 T lymphocytes. The key feature of untreated HIV-1 infection is the progressive depletion of CD4 T lymphocytes. The major achievement of potent antiretroviral therapy (ART)
BMC Infectious Diseases, 2011
Background: Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. Methods: T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30].
AIDS Research of Human Retroviruses, 2022
We present a cohort of individuals who reached CD4 + T cell counts of greater than 1,000 cells/mm 3 (Hypers) after starting antiretroviral treatment (ART) and compared them with those who reached between 350 and 999 CD4 + T cells/mm 3 (Concordants). Demographic data, immune recovery kinetics, T CD4 + subset phenotypes, and integrated HIV DNA were analyzed. Data from individuals living with HIV on their first ART regimen and after 48 months of follow-up were obtained. Immune phenotype by Flow Cytometry analysis on whole blood was performed, cytokines were measured, and integrated HIV-1 DNA was measured by polymerase chain reaction. From a total of 424 individuals, 26 Hypers (6.1%), 314 Concordants (74.1%), and 84 (19.8%) discordants were identified. Hypers had a higher proportion of CD4 +-naive (Nv) T cells (37.6 vs. 24.8, p < .05), and a low proportion of CD4 + effector memory T cells (27.9 vs. 39.4, p < .05), with similar results found in CD8 + T cells. Hypers demonstrated a higher percentage of CD4 + CD45RA + CD31 neg cells with a lower response to interleukin-2 stimulation and a lower integrated HIV-1 DNA/CD4 ratio (1.2 vs. 2.89, p < .05). In Hypers, T cell recovery occurs very early after initiation of ART. Following this initial recovery state, their CD4 + T cell level homeostasis seems to be driven by nonthymic-central-Nv cells. This exceptional recovery is associated with a lower HIV reservoir, which may be related to an increase in noninfected CD4 + T cells. These patients could then be eligible candidates for cure trials.
Clinical Microbiology and Infection, 2012
We evaluated factors associated with normalization of the absolute CD4+ T-cell counts, per cent CD4+ T cells and CD4+/CD8+ T-cell ratio. A multicentre observational study was carried out in patients with sustained HIV-RNA <50 copies/mL. Outcomes were: CD4count >500/mm 3 and multiple T-cell marker recovery (MTMR), defined as CD4+ T cells >500/mm 3 plus %CD4 T cells >29% plus CD4+/CD8+ T-cell ratio >1. Kaplan-Meier survival analysis and Cox regression analyses to predict odds for achieving outcomes were performed. Three hundred and fifty-two patients were included and followed-up for a median of 4.1 (IQR 2.1-5.9) years, 270 (76.7%) achieving a CD4+ T-cell count >500 cells/mm 3 and 197 (56%) achieving MTMR. Using three separate Cox models for both outcomes we demonstrated that independent predictors were: both absolute CD4+ and CD8+ T-cell counts, %CD4+ T cells, a higher CD4+/ CD8+ T-cell ratio, and age. A likelihood-ratio test showed significant improvements in fitness for the prediction of either CD4+ >500/ mm 3 or MTMR by multivariable analysis when the other immune markers at baseline, besides the absolute CD4+ count alone, were considered. In addition to baseline absolute CD4+ T-cell counts, pretreatment %CD4+ T cells and the CD4+/CD8+ T-cell ratio influence recovery of T-cell markers, and their consideration should influence the decision to start antiretroviral therapy. However, owing to the small sample size, further studies are needed to confirm these results in relation to clinical endpoints.
Antiviral therapy
Methods: Treatment-naive patients in the Swiss HIV Cohort Study reaching two VL measurements <50 copies/ml >3 months apart during the 1st year of cART were included (n=1,816 patients). We studied CD4 + T-cell dynamics until the end of suppression or up to 5 years, subdivided into three periods: 1st year, years 2-3 and years 4-5 of suppression. Multiple median regression adjusted for repeated CD4 + T-cell measurements was used to study the dependence of CD4 + T-cell slopes on clinical covariates and drug classes.