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Biomedical subjects

Luca Meroni

Publications and source records attributed to Luca Meroni.

12 recordsLinked to original sources
PubMed2006

Comparative analysis of T-cell turnover and homeostatic parameters in HIV-infected patients with discordant immune-virological responses to HAART.

OBJECTIVE: Inadequate CD4 cell count recovery despite full HIV RNA control occurs in 30% of HAART-treated HIV-infected patients. A better understanding of the relationship between T-cell dynamics and the HIV intracellular reservoir in HIV-infected patients failing to recover CD4 cell count following long-term HAART, is required. METHODS: In a cross-sectional study T-cell turnover and homeostatic parameters featuring discordant responses were investigated in 27 immunologic non-responders (INR; CD4 count, < or = 200 cells/microl; HIV RNA, < or = 50 copies/ml), 15 virological non-responders (VNR; CD4 count, > or = 350 cells/microl; HIV RNA, > or = 10 000) and 22 full responders (FR; CD4 count, > or = 500 cells/microl; HIV RNA, < or = 50 copies/ml). RESULTS: INR displayed significantly higher activated CD38CD8 than FR (P < 0.05) and was comparable to VNR (P > 0.05). As compared with VNR and FR, INR displayed the highest level of proliferating Ki67CD4 and apoptotic CD4 cells (P < 0.05). VNR presented lower proliferation and apoptosis than FR and INR. INR displayed the lowest levels of naive T cells (P < 0.05) and a predominant memory pattern. Despite the memory/activated/apoptotic phenotype, INR showed a statistically non-significant reduction in T-cell receptor excision circles (TREC) compared to FR (P > 0.05), and substantially heightened interleukin (IL)-7 (P < 0.05), while VNR showed higher naive T-cell counts and TREC. Moreover, the reservoir of infected CD4 cells was increased in INR, with a trend toward highest intracellular HIV DNA within total, naive and memory CD4 cells. CONCLUSIONS: The lack of CD4 cell count recovery in INR seems to reflect a highly activated apoptotic T-cell compartment, with elevated IL-7 and thymic impairment. High levels of intracellular HIV-DNA in INR could be strictly involved in the lack of T-cell reconstitution. Immune correlates of an ultimate direction of the response to HAART, could be exploited in clinical practice for the most effective management of discordant patients, to amend immune imbalances and to improve clinical outcome.

Adult↗
PubMed2005

Increased CD36 expression on circulating monocytes during HIV infection.

BACKGROUND: Metabolic alterations and abnormalities of fat distribution are common findings in antiretroviral-treated HIV-1-infected patients. CD36 is a multifunctional receptor with a wide tissue distribution that plays a crucial role in the cellular uptake and metabolism of lipids. OBJECTIVES: To define the level of CD36 expression on circulating monocytes from HIV-1-infected patients and healthy controls (HCs) and to correlate CD36 expression levels with metabolic and immunovirologic parameters. METHODS: CD36 expression on peripheral blood monocytes was measured by means of flow cytometry in 165 HIV-1-infected patients and in 35 HCs. Statistical analysis was performed by means of univariate and multivariate analysis of variance models. RESULTS: CD36 expression was significantly higher in HIV-1-infected patients compared with HCs (P < 0.0001). HIV-1 infection was the only variable associated with CD36 expression on multivariate analysis, whereas no correlation was found between CD36 level and age, sex, body mass index, lipid serum levels, HIV RNA levels, time on antiretroviral therapy, or kind of antiretroviral regimen. CONCLUSIONS: HIV-1 infection is associated with increased expression of CD36 on circulating monocytes, and antiretroviral drugs play only a minor role in the complex homeostasis of this receptor. Given its role in the cellular uptake and accumulation of lipids, CD36 increased levels on monocytes could represent a proatherogenic condition in HIV-infected patients.

Adult↗
PubMed2004

Interleukin-2 immunotherapy exerts a differential effect on CD4 and CD8 T cell dynamics.

BACKGROUND: Emerging evidence indicates that CD4 and CD8 T cell recovery is differentially regulated during HIV infection. The hallmark of interleukin-2 (IL-2)-induced immune reconstitution is the selective outgrowth of CD4 through undefined mechanisms. OBJECTIVE: To delineate the effect of IL-2 on T cell homeostasis by analysing the differential impact of IL-2 immunotherapy on CD4 and CD8 dynamics. DESIGN: A randomized trial of 15 HIV-positive patients, eight receiving IL-2 immunotherapy with highly active antiretroviral therapy (HAART) and seven with HAART alone. Patients were followed for a 48-week period following three IL-2 cycles (overall, 10 weeks in duration). METHODS: CD4 and CD8 count, naive and memory immunophenotype, proliferation by Ki67, and CD8+CD38+ activated pattern were measured longitudinally by flow cytometry. Thymic output contribution to both CD4 and CD8 was evaluated by measurement of T cell receptor excision circles (TREC). Wilcoxon test was used to compare results. RESULTS: Compared with changes seen with HAART alone, IL-2 induced a more significant rise in CD4 than CD8 T cell count (P < 0.01), associated with a significant increase in Ki67-proliferating CD4 (P < 0.05), whereas no changes were seen in CD8+Ki67+ (P > 0.05). Furthermore, IL-2 administration was associated with CD4 TREC increase, whereas CD8 TREC remained stable (P > 0.05). Modifications in CD4 and CD8 T cells seen in patients taking only HAART were not associated with changes in CD4 and CD8 TREC. CONCLUSIONS: By showing a differential impact on CD4 and CD8 homeostasis, the study suggests that IL-2-associated immune reconstitution results from protean interactions between T cell compartments; this has significant implications for the correct planning of immunotherapeutic strategies.

Adult↗
PubMed2004

IL-7/IL-7 receptor system regulation following IL-2 immunotherapy in HIV-infected patients.

Interleukin-2 (IL-2) and IL-7 are the most intriguing molecules in immune-based HIV infection treatment. An in vitro IL-2/IL-7 cross-talk due to IL-2-driven IL-7 receptor-alpha-chain (IL-7R alpha) down-modulation, potentially blocking IL-7 signalling has been described. We investigated the in vivo IL-2 effect on IL-7/IL-7R system, measuring free IL-7, and IL-7R alpha CD4 and CD8 in 12 HIV-positive patients enrolled in a randomized IL-2 trial. Compared to HAART alone, IL-2 induced a parallel expansion in total and naive CD4, TRECs and IL-7 plasma levels, with no IL-7R alpha CD4 and IL-7R alpha CD8 changes (P>0.05), suggesting that in vivo IL-2 boosts IL-7 production without down-modulating IL-7R alpha, preserving IL-7-mediated T-lymphocyte homeostatic regulation. Our data confirm the pivotal role of IL-2 and IL-7 in the regulation of T-lymphocyte homeostasis in HIV infection.

Anti-HIV Agents↗
PubMed2003

Cytokine production in women with antiretroviral treatment-associated breast fat accumulation and limb wasting.

OBJECTIVE: To test the cytokine production of peripheral blood mononuclear cells in a group of HIV-infected women with breast enlargement and lower limb wasting while receiving antiretroviral therapy (ART) including a protease inhibitor. DESIGN: Case-control study including 20 women with fat tissue alterations and 20 matched controls treated with comparable ART. METHODS: Adipose tissue alterations (ATA) were defined by increased breast size (> or = 2 bra sizes) accompanied by lower limb fat wasting. A randomly selected subset of patients underwent analyses including: dual energy X-ray absorptiometry, metabolic and endocrine assays, in vitro cytokine production testing [interferon-gamma, interleukin (IL)-2, IL-4, IL-10, IL-12, tumor necrosis factor-alpha (TNF-alpha)] after appropriate stimulation; T-cell phenotyping, T-helper function after stimulation with either tetanus toxoid, influenza antigen, allogeneic peripheral blood lymphocytes, and phytohemagglutinin. Endocrinological study included the determination of plasma concentrations of prolactin, growth hormone, testosterone, adrenocorticotropic hormone, cortisol and C-peptide. RESULTS: In vitro production of IL-12 was higher (P = 0.0001), and TNF-alpha (P = 0.0093) and IL-10 (P < 0.0001) production were lower in stimulated peripheral blood mononuclear cells of ATA-positive women compared with ATA-negative women. ATA-positive women also showed a better response to tetanus toxoid (P = 0.021) and a lower median fluorescence intensity of CD14/DR (P=0.033). Plasma C-peptide values were higher in ATA-positive women compared with ATA-negative women (P = 0.033), even if in the normal range (< 4 ng/ml) in all but one of the ATA-positive patients. CONCLUSION: HIV-1-infected women who developed breast enlargement and lower limb fat wasting while receiving ART had a favorable immunological profile with efficient IL-12 production and T-helper function, and with TNF-a production in the range of a HIV-negative reference population. These findings suggest that the rescue of some immune functions under ART may be involved in the pathogenesis of this particular adipose tissue disorder.

Absorptiometry, Photon↗
PubMed2002

Low-dose prolonged intermittent interleukin-2 adjuvant therapy: results of a randomized trial among human immunodeficiency virus-positive patients with advanced immune impairment.

Twenty-two patients with CD4(+)cell counts <or=200 cells/microL after 12 months of stable highly active antiretroviral therapy (HAART; "immunologic nonresponders") were randomly assigned to receive subcutaneous low-dose prolonged intermittent interleukin (IL)-2 in addition to HAART (n=12) or to continue HAART alone (n=10). At 48 weeks of follow-up, no IL-2-related serious adverse events and no significant differences in plasma human immunodeficiency virus (HIV) RNA level were observed in the 2 groups. A higher incidence of HIV-related clinical events was observed among patients receiving HAART alone (3/10) than among subjects receiving HAART plus IL-2 (0/12). Significant increases in CD4(+), naive, and CD4(+)CD7(+) cells and plasma levels of IL-7 were observed in patients receiving IL-2 versus patients receiving HAART alone. A significant increase in cell turnover did not lead to a decrease in the frequency of T cell receptor excision circles, which remained stable. Rather, increased numbers of T cell receptor excision circles per microliter of blood were observed (not statistically significant). Thus, adjuvant IL-2 therapy in immunologic nonresponders resulted in a clinical benefit, suggesting that the quantitative cell recovery involves functionally competent immune cells.

Adult↗
PubMed2002

Emergence of multiple drug-resistant human cytomegalovirus variants in 2 patients with human immunodeficiency virus infection unresponsive to highly active antiretroviral therapy.

In 2 patients infected with human immunodeficiency virus (HIV), highly active antiretroviral therapy was unable to suppress HIV replication as a result of the emergence of drug-resistant HIV variants. Human cytomegalovirus (HCMV) retinitis developed in both patients, and an unusually complex mixture of drug-resistant HCMV variants was detected in both patients.

AIDS-Related Opportunistic Infections↗