Abstract
IntroductionT-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection.Patients and methods96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31–60] months. PD1 and Tim3 expression, CD8 T-cells activation, recent thymic emigrants, activation/apoptosis and turnover of CD4 cells were assessed at baseline and during follow up. Univariate and multivariate associations with CD4 evolution were explored.ResultsParameters significantly associated with CD4 depletion in cART-naïve group were: baseline level (p = 0.02) and variation (p = 0.002) of PD1 and Tim3 co-expression on CD8, and variation of CD95 expression on CD4 (p = 0.007). Parameters significantly associated with CD4 restoration in cART group were: baseline level of CD38+HLADR- subset of CD8 (p = 0.01), variation of PD1 expression on CD8 (p = 0.036), variation of Tim3 expression on CD4 (p = 0.039) and variation of CD95 expression on CD4 (p = 0.035).ConclusionsOur results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection.
Highlights
Methods96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31–60] months
T-cell exhaustion has been involved in the pathogenesis of HIV infection
Our results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection
Summary
96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31–60] months. Univariate and multivariate associations with CD4 evolution were explored This is a retrospective longitudinal study including two different groups of patients with chronic HIV infection: one with a long-term period of follow up in the absence of any. T-cells exhaustion and CD4 dynamics antiretroviral therapy (cART naïve group), and another with a long-term period of follow up from the initiation of cART and maintaining undetectable levels of plasma HIV-RNA (cART group). Inclusion criteria were: adult with chronic HIV infection and regular immunovirological (CD4 counts and plasma HIV-RNA load) follow up, naïve for cART during the follow up period (for the cART naïve group), initiating cART and achieving and maintaining undetectable plasma HIV-load during the follow up period (for the cART group), naïve for anti-HCV treatment (for those patients co-infected with HCV), and with a cellular sample at the beginning of follow up (baseline sample) available for immunophenotyping. To participate in the study, written informed consent was obtained from all individuals, and the study protocol was evaluated and approved by the Ethical Committee of Hospital Carlos III-La Paz
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