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Chronic HIV Infection (chronic + hiv_infection)
Selected AbstractsPeripheral CD4 loss of regulatory T cells is associated with persistent viraemia in chronic HIV infectionCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007C. A. R. Baker Summary Chronic HIV infection is associated with T cell abnormalities and altered effector function. Regulatory T cells (Treg) are CD4+ T cells that play a critical role in regulating the immune system. The impact of regulatory T cells on HIV infection and disease progression may be highly significant. We hypothesize that chronic antigenic stimulation from a persistent, high viraemic state may promote a population of Treg that contributes to HIV-associated immune dysfunction. We evaluated the pattern of Treg in chronically infected, HIV-positive individuals over a course of 6 months. Treg are depleted at a distinct rate from that of absolute CD4 cells and loss of Treg is slower in the presence of viral suppression. In vitro depletion of CD25+ CD4+ cells resulted in increased Gag-specific CD4 and CD8 responses. A significant correlation between ex vivo measurement of Treg and Gag-specific CD4 T cell responses was observed (r = ,0·41, P = 0·018) with a trend observed with Gag-specific CD8 T cell responses (P = 0·07). The impact of HIV infection on the Treg population directly complicates the measured effect of Treg on the immune dysfunction although our data support the important role of Treg on modulating the effector T cell response in chronic infection. [source] Extended antiretroviral treatment interruption in HIV-infected patients with long-term suppression of plasma HIV RNAHIV MEDICINE, Issue 1 2005CJ Achenbach Objectives Evaluation of extended treatment interruption (TI) in chronic HIV infection among patients successfully treated with antiretroviral therapy. Methods An observational analysis of 25 patients in a prospectively followed cohort with chronic HIV infection, viral loads <500 HIV-1 RNA copies/mL for at least 6 months, and an interruption in therapy of ,28 days duration was carried out. Follow up was divided into 3-month time periods for analysis. The effects of time period, stratification group and stratification group by time period interactions on CD4 counts were tested using a mixed model. Univariate comparisons among patient characteristics and responses were performed using Fisher's exact test or the Wilcoxon rank sum test. Results At initiation of TI, the median CD4 count was 799 cells/,L. TI duration was a median of 7.1 months. HIV RNA rebounded to a median maximum level of 75 000 copies/mL. Maximum viral rebound was significantly greater in patients who were male, had lipodystrophy and had zenith HIV RNA prior to TI of ,50 000 copies/mL. Lower CD4 cell counts were observed during TI in patients with lipodystrophy, zenith HIV RNA ,50 000 copies/mL, history of AIDS, HIV infection ,5 years and presuppression CD4 count ,350 cells/,L. Patients who reinitiated therapy had shorter TI duration, presuppression CD4 count ,350 cells/,L, previous AIDS diagnosis and lipodystrophy. No patients developed adverse or AIDS-defining events during TI. Conclusions Long-term TI resulted in greater immune deterioration in patients with high viral set points or low CD4 cell counts prior to initiation of suppressive antiretroviral therapy. [source] Evidence of thymic reconstitution after highly active antiretroviral therapy in HIV-1 infectionHIV MEDICINE, Issue 2 2004G Hardy Objectives We aimed to provide evidence of thymic reconstitution after highly active antiretroviral therapy (HAART) in HIV-1 infected patients and to correlate this with the restoration of peripheral naïve T cells. Methods Positron emission tomography (PET) enables definitive evidence of thymic activity, indicating functional potential. In this case study, a single patient who initiatiated HAART demonstrated reconstitution of the naïve T-cell pool and underwent thymic PET scans at baseline and 2 and 6 months following initiation of therapy. Two patients who failed to demonstrate such reconstitution acted as controls. These patients (mean age 27 years) had chronic HIV infection with low CD4 T-cell counts (mean 82, range 9,160 cells/,L blood). Increased function of the thymus visualized by PET was correlated with phenotypic changes in CD4 and CD8 T cells in the periphery measured by flow cytometry, and with numbers of recent thymic emigrants measured by quantification of the numbers of T-cell receptor excision circles (TRECs) in peripheral cells. Results In one patient, clear correlations could be drawn between visible activity within the thymus, as measured by increased [F18]fluorodeoxyglucose (FDG) uptake, and regeneration of naïve CD4 (CD45RA/CD62L) T cells, increased numbers of CD4 T cells, controlled viraemia and increased numbers of recent thymic emigrants. A second patient displayed no increase in peripheral CD4 count and no increase in thymic activity. The third patient elected to stop therapy following the 2-month time point. Conclusions The use of PET suggests that thymic activity may increase after HAART, indicating that the thymus has the potential to be functional even in HIV-1 infected persons with low CD4 T-cell counts. [source] Significant link between sCD30 changes and HIV viremia in patients treated with HAART,JOURNAL OF MEDICAL VIROLOGY, Issue 12 2006Priscilla Biswas Abstract Elevated sCD30 levels were generally associated with poor prognosis in chronic HIV infection prior to the era of highly active antiretroviral therapy (HAART). Little information is available on sCD30 and HIV-1 viremia. In this study, the association between sCD30 and HIV-1 viremia was investigated in HIV-infected patients who underwent HAART. sCD30 was measured in 276 patients prior (T0) and 6 months after HAART (T6). Standard survival analyses were used to evaluate the prognostic value of sCD30 and sCD30 change from baseline to predict the virological response to HAART. Higher levels (>30 U/ml) of sCD30 prior to HAART were associated with relatively higher viremia (P,=,0.0001) and tended to be associated with a lower chance of achieving virological success (P,=,0.13). The median T6 sCD30 level in patients who concomitantly had viremia >500 copies/ml was higher than the median sCD30 level of those with viremia ,500 copies/ml (P,=,0.002). Conversely, within the patients who achieved viral suppression on HAART, those who had concomitantly a larger reduction in sCD30 subsequently experienced a higher rate of virological failure (P,=,0.04). A strong, but complex, link exists between sCD30 levels and HIV viremia in the era of HAART. The change in sCD30 levels from pre-therapy to the date of first viral suppression could be used to identify patients who are more likely to experience later virological rebound among those who achieve initially virological success. J. Med. Virol. 78:1513,1519, 2006. © 2006 Wiley-Liss, Inc. [source] Interleukin-2 reconstitutes defective human immunodeficiency virus (HIV), and cytomegalovirus (CMV) specific CD8+ T cell proliferation in HIV infectionJOURNAL OF MEDICAL VIROLOGY, Issue 9 2006Jie Yu Abstract Recent studies indicate that a defective proliferative response of HIV-specific CD8+ T cells is associated with the lack of virologic control in chronic HIV infection in humans. The possible mechanisms that might be responsible for the reduced proliferative potential of HIV-specific CD8+ T cells and conditions conducive to the proliferation of CD8+ T cells were examined in 14 HIV-infected individuals and 7 HIV-uninfected controls using CFSE labeling and flow cytometry techniques, and analyzed data using 2 quantitative measurements: the percentages of proliferating CD8+ T cells (Tp), and the maximum number of cell divisions (Dm) after stimulation. It was found that CD8+ T cells from HIV-infected and -uninfected subjects proliferated equally well after polyclonal stimulation by phylohemagglutinin A (PHA); both groups reached a Tp of 92%,96% and a Dm of 5,8. However, in HIV-infected subjects, proliferation of HIV- and CMV-specific CD8+ T cells was significantly reduced compared to proliferation of CMV- specific CD8+ T cells from HIV-uninfected subjects. These defective proliferative responses of HIV- and CMV-specific CD8+ T cells were restored by the addition of IL-2 at the time of stimulation. These results may have implications for the design of immune modulation strategies in vivo. J. Med. Virol. 78:1147,1157, 2006. © 2006 Wiley-Liss, Inc. [source] Peripheral CD4 loss of regulatory T cells is associated with persistent viraemia in chronic HIV infectionCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007C. A. R. Baker Summary Chronic HIV infection is associated with T cell abnormalities and altered effector function. Regulatory T cells (Treg) are CD4+ T cells that play a critical role in regulating the immune system. The impact of regulatory T cells on HIV infection and disease progression may be highly significant. We hypothesize that chronic antigenic stimulation from a persistent, high viraemic state may promote a population of Treg that contributes to HIV-associated immune dysfunction. We evaluated the pattern of Treg in chronically infected, HIV-positive individuals over a course of 6 months. Treg are depleted at a distinct rate from that of absolute CD4 cells and loss of Treg is slower in the presence of viral suppression. In vitro depletion of CD25+ CD4+ cells resulted in increased Gag-specific CD4 and CD8 responses. A significant correlation between ex vivo measurement of Treg and Gag-specific CD4 T cell responses was observed (r = ,0·41, P = 0·018) with a trend observed with Gag-specific CD8 T cell responses (P = 0·07). The impact of HIV infection on the Treg population directly complicates the measured effect of Treg on the immune dysfunction although our data support the important role of Treg on modulating the effector T cell response in chronic infection. [source] Absence of favourable changes in circulating levels of interleukin-16 or ,-chemokine concentration following structured intermittent interruption treatment of chronic human immunodeficiency virus infectionCLINICAL MICROBIOLOGY AND INFECTION, Issue 1 2005M. Montes de Oca Arjona Abstract Changes in virological and immunological parameters were analysed following structured intermittent interruption of highly active anti-retroviral therapy (HAART) of patients with chronic human immunodeficiency virus (HIV) infection. Parameters analysed were serum levels of the CD8+ T-cell-derived inhibitory molecules interleukin-16 (IL-16), monocyte inhibitory protein-1, (MIP-1,) and RANTES (,regulated upon activation, normal T-cell expressed and presumably secreted'), and the enhancer of HIV replication, monocyte chemotactic protein-1 (MCP-1). Twenty-five patients with chronic HIV infection were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off) in comparison with 20 healthy sex- and age-matched controls. At enrolment, HIV-infected patients showed significantly higher serum concentrations of IL-16 and RANTES, and significantly lower concentrations of MCP-1, than did healthy controls. Levels of MIP-1, were similar in both groups. Only the serum levels of IL-16 increased significantly in HIV-infected patients after every treatment interruption. However, differences between the CD4+ or CD8+ T-cell counts/µL, HIV loads and serum concentrations of each cytokine at baseline and at the end of the three cycles of intermittent interruptions of therapy were not significant. It was concluded that structured intermittent interruption of HAART for patients with chronic HIV infection did not modify the immunological parameters, including serum levels of CD8+ T-cell-derived inhibitory molecules, or the virus parameters studied. Thus, the findings do not support the use of this treatment modality for the management of HIV-infected patients. [source] | ||||||||||