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Biomedical subjects

G Rizzardini

Publications and source records attributed to G Rizzardini.

At least 19 recordsLinked to original sources
PubMed2001

Evaluation of immune activation in HIV-infected and uninfected African individuals by single-cell analysis of cytokine production.

Immune activation has been observed in HIV-infected and uninfected Africans, among whom it is thought to modify interaction between the immune system and HIV. To characterize this phenomenon accurately, in-depth immunologic analyses were performed in a rural African population. Freshly drawn peripheral blood mononuclear cells (PBMCs) of HIV-infected African (from Gulu, Uganda) and Italian antiviral-naive patients and those of uninfected Ugandan and Italian study subjects were analyzed. Individuals were matched for age and sex and determined to be free from parasitic infections. Intracellular cytokines were measured in mitogen (M)- and gp160 peptides + staphylococcal enterotoxin B and alpha CD28 (env)-stimulated T lymphocytes. Interferon (IFN)-gamma-producing CD8(+) T cells were quantified in an enzyme-linked immunosorbent assay. Results showed that M-stimulated production of interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha increases in CD4(+) and CD8(+) cells of African infected patients and uninfected study subject; and that env-stimulated IL-10 and TNF-alpha production is increased in CD8(+) T lymphocytes of African HIV-infected patients. M- and env-stimulated IFN-gamma-producing CD8(+) T cells were reduced in African participants and not increased by preincubation with alpha IL-10 monoclonal antibody. This is the first set of data that has reported immune activation in rural Africa by single-cell analysis of cytokine production. These results help in defining the immunologic background to be considered in the design of therapeutic and vaccine-based approaches to HIV infection in an African setting.

Black People↗
PubMed2001

Increasing prevalence of non-clade B HIV-1 strains in heterosexual men and women, as monitored by analysis of reverse transcriptase and protease sequences.

OBJECTIVE: We evaluated the prevalence of HIV-1 non-clade B over time in a formerly clade B-restricted area. Protease and reverse transcriptase regions of the pol gene were used for phylogenetic and recombination analysis and for clade assignment to HIV-1 A-D, F-H, J, and K strains of the M group. METHODS: The pol gene of 349 HIV-1 patients belonging to the Italian Cohort Naive for Antiretrovirals (ICONA) were genotypically analyzed to study the prevalence of antiretroviral-associated resistance mutations. All HIV-1 pol sequences and 32 HIV reference strains were analyzed, including the reference strains for the major HIV-1 subtypes. The non-clade B sequences according to the HIV-1 Subtyping Tool program were further studied by a bootscan analysis (SimPlot) to investigate the likelihood of recombination between subtypes. RESULTS: Phylogenetic analysis detected 19 of 349 (5.4%) non-clade B subtypes. The proportions of patients carrying non-clade B virus before and after 1997 were 1.9% and 8.4%, respectively (p =.008). Among whites, heterosexual infection and female gender were significantly associated with the presence of non-clade B subtypes (p =.001 and.005, respectively). Non-clade B HIV-1 was harbored by 14.5% of the heterosexuals who were found to be HIV-1 positive after 1997, 60% of whom were women. Bootscan analysis identified four strains as F, two as A, one as C, one as G, and 11 (57.9 %) as non-clade B recombinant subtypes. CONCLUSION: Detection of HIV-1 subtypes and intersubtype recombinants in a previously clade B-homogeneous area indicates that the HIV-1 epidemic is evolving in Italy and that heterosexuals and women are at increased risk of infection with non-clade B HIV-1 subtypes. Sequences inferred from the pol gene yield to establish the subtype of circulating HIV-1 strains. As a consequence, genotyping of pol gene for testing resistance to antiretrovirals warrants concomitant surveillance of non-clade B subtypes.

Adult↗
PubMed2000

Immune activation in africa is environmentally-driven and is associated with upregulation of CCR5. Italian-Ugandan AIDS Project.

BACKGROUND: HIV infection in Africa is associated with immune activation and a cytokine profile that stimulates CCR5 expression. We investigated whether this immune activation is environmentally driven; if a dominant expression of CCR5 could indeed be detected in African individuals; and if R5 HIV strains would be prevalent in this population. METHODS: Freshly drawn peripheral blood mononuclear cells from HIV-uninfected African and Italian individuals living in rural Africa, from HIV-uninfected Africans and Italians living in Italy, and from HIV-infected African and Italian patients were analysed. Determinations of HIV coreceptor-specific mRNAs and immunophenotype analyses were performed in all samples. Virological analyses included virus isolation and characterization of plasma neutralizing activity. FINDINGS: Results showed that: immune activation is detected both in Italian and African HIV-uninfected individuals living in Africa but not in African subjects living in Italy; CCR5-specific mRNA is augmented and the surface expression of CCR5 is increased in African compared with Italian residents (CXCR4-specific mRNA is comparable); R5-HIV strains are isolated prevalently from lymphocytes of African HIV-infected patients; and plasma neutralizing activity in HIV-infected African patients is mostly specific for R5 strains. CONCLUSIONS: Immune activation in African residents is environmentally driven and not genetically predetermined. This immune activation results in a skewing of the CCR5 : CXCR4 ratio which is associated with a prevalent isolation of R5 viruses. These data suggest that the selection of the predominant virus strain within the population could be influenced by an immunologically driven pattern of HIV co receptor expression.

Africa↗
PubMed2000

Plasma viral load concentrations in women and men from different exposure categories and with known duration of HIV infection. I.CO.N.A. Study Group.

CONTEXT: According to recent studies, women have lower plasma HIV RNA concentrations than men. However, these studies did not take into account the duration of HIV infection. OBJECTIVES: To analyze the relationship between viral load and gender among individuals with known date of seroconversion. SETTING: Sixty infectious disease clinics in Italy. DESIGN: Cross-sectional analysis of data collected at enrollment in a cohort study. PARTICIPANTS: Injecting drug users and heterosexual contacts naive to antiretroviral therapy at enrollment (245 men; 170 women). MAIN OUTCOME MEASURES: Plasma HIV RNA concentrations, measured using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or signal amplification b-DNA assays before antiretroviral therapy. RESULTS: Plasma HIV RNA concentrations were similar by age and exposure category (p =.80 and p =.39, respectively). Median viral load among women was roughly half that of men (p =.002). The association between viral load and gender remained significant after fitting a two-way analysis of variance (p =.03) and after adjusting for CD4 count, modality of HIV transmission, and age at enrollment in a regression model. Viral load was 0.27 log10 copies/ml (95% confidence interval, 0.05-0.40; p =.01) lower in women (i.e., 50% lower in the raw scale). CONCLUSIONS: Plasma HIV RNA concentrations were found to be lower among women, even when considering the duration of HIV infection. Compared with men, it is possible women should be given highly aggressive antiretroviral therapy at lower HIV-RNA concentrations.

Adolescent↗
PubMed2000

Role of brain biopsy in the management of focal brain lesions in HIV-infected patients. Gruppo Italiano Cooperativo AIDS & Tumori.

In this multicenter, retrospective study of 160 brain biopsies in the assessment of HIV-related focal brain lesions, diagnostic sensitivity was acceptable (87%), but the procedure carried considerable morbidity (7.5%) and mortality (3.1%). Moreover, it is not always possible to initiate the changes in therapy indicated by the results, and overall survival remains poor, with a median of 2 months. Criteria for brain biopsy for the diagnosis of focal brain lesions should be redefined to include selected patients for whom a less invasive approach does not yield a definitive diagnosis.

Adult↗
PubMed2000

In vitro immunomodulatory properties of tucaresol in HIV infection.

The immunomodulatory properties of tucaresol (compound 589C80) were tested on in vitro antigen- and mitogen-stimulated proliferation and cytokine production by peripheral blood mononuclear cells (PBMC) of HIV-infected individuals and healthy controls (HC). Results showed that tucaresol: (1) increases influenza A virus-, gp 160 peptide-, and HLA alloantigen-stimulated proliferation as well as interleukin (IL)-2 and interferon gamma (IFN gamma) production by PBMC of HIV-infected individuals with higher CD4 counts (>500/microl) but had only a marginal immunomodulatory effect on PBMC of patients with lower CD4 counts (<500/microl); (2) did not modify IL-10 production; (3) augmented CD25 expression on mitogen-stimulated T cells of HC but not of HIV-infected individuals; and (4) marginally increased CTL activity. The immunomodulatory properties of tucaresol were confirmed by PCR analyses; additional data showed that tucaresol costimulated CD3-dependent triggering of T cells and that this stimulation was independent of CD28 costimulation. The immunomodulatory effects of tucaresol on T cell functions are characterized by a bell-shaped dose response curve; the action of the compound is optimal in the 100 to 300 microM range. Analyses of mitogen-stimulated apoptosis demonstrated that the lack of effect of tucaresol at higher doses is not the result of increased cell death, suggesting a role of functional impairment. These data confirm that tucaresol can stimulate T helper cell function and enhance the production of type 1 cytokines, thus eliciting cell-mediated immunity, and warrant its potential utility in the therapy of HIV infection.

Adjuvants, Immunologic↗
PubMed2000

Effect of two different combinations of antiretrovirals (AZT+ddI and AZT+3TC) on cytokine production and apoptosis in asymptomatic HIV infection.

Nineteen HIV-seropositive antiretroviral therapy-naive and asymptomatic individuals (200-500 CD4/microl) were enrolled in a prospective study aimed at analyzing the immunologic and virologic effects of two different combinations of nucleoside reverse transcriptase inhibitors (AZT+ddI and AZT+3TC), and randomly assigned to one of the treatment group. Immunologic (CD4 and CD8 counts, mitogen-stimulated cytokine production, unstimulated and mitogen-stimulated apoptosis) and virologic (HIV viral load) determinations were performed pre-therapy and 15, 30, 90, 200 and 360 days after initiation of therapy. Results showed that the two combinations had comparable effects on increasing CD4 counts and the CD4/CD8 ratio and in reducing HIV viral load. In contrast, AZT+3TC was more efficient in improving interleukin-2 (IL-2) and interferon gamma (IFNgamma) production as well as the type 1/type 2 cytokine ratio and in down modulating the susceptibility of peripheral blood mononuclear cells to in vitro mitogen-stimulated apoptotic cell death. These data suggest that the combination of AZT+3TC has a stronger effect on potentially beneficial immune parameters (IL-2 production; reduction of apoptosis) than the one between AZT+ddI. The combination of AZT+3TC could be more advantageous in the therapy of HIV infection even when used in association with a protease inhibitor.

Anti-HIV Agents↗
PubMed2000

Vinorelbine is an effective and safe drug for AIDS-related Kaposi's sarcoma: results of a phase II study.

PURPOSE: To assess the safety and efficacy of vinorelbine in patients with AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: From December 1994 to May 1997, within the Italian Cooperative Group on AIDS and Tumors, we enrolled 36 patients with AIDS-related KS who experienced disease progression after one or more regimens of systemic chemotherapy. Patients were treated with vinorelbine 30 mg/m(2) every 2 weeks by intravenous bolus. RESULTS: Of 35 assessable patients, three (9%) had a clinical complete response and 12 (34%) had a partial remission, for an overall objective response rate of 43% (95% confidence interval, 26% to 61%). For the 15 patients with objective responses, the median duration of response from the beginning of therapy until the development of progression was 176 days, whereas the median progression-free survival and the median survival durations for 35 assessable patients were 151 days and 216 days, respectively. Vinorelbine also induced responses in patients who had become resistant to regimens that included other vinca alkaloids. Overall, vinorelbine was well tolerated. Toxicity, including neurologic toxicity, was mild and reversible. Neutropenia was the most frequent dose-limiting toxicity. CONCLUSION: Vinorelbine is safe and effective in the treatment of patients with advanced KS who have been previously treated with one or more chemotherapy regimens.

Acquired Immunodeficiency Syndrome↗
PubMed1999

AIDS-associated Kaposi's sarcoma is more aggressive in women: a study of 54 patients.

OBJECTIVE: To describe the epidemiologic and clinical features of AIDS-associated Kaposi's sarcoma (KS) in women compared with men. METHODS: In a retrospective study, within the Italian Cooperative Group on AIDS and Tumors (GICAT), we compared selected characteristics of 54 women and 108 men with AIDS-associated KS, matched by date of KS diagnosis and referral hospital. The chi2 test was used to test differences among proportions; the Kaplan-Meier method to estimate the survival time, and the Cox proportional hazard model was used to assess the role of gender, age, and CD4 cell count on death's risk. RESULTS: KS occurred at an earlier age (p = .001), was associated with a more severe immunodeficiency (p = .03), more advanced stages of HIV disease (p = .05), and had more aggressive presentation and course in women than in men. At KS diagnosis, women had a significantly increased proportion of visceral disease (p = .009), in particular pulmonary involvement (p = .002) and atypical sites of involvement (p = .008). The number of deaths due to KS was significantly higher (p = .01) in female patients. Both the higher proportion of visceral disease and of KS-related deaths observed in women did not change after adjusting for CD4 cell count and age. Women showed a decreased overall survival compared with men (8.9 and 14.4 months, respectively; p = .07), and the CD4 cell count at diagnosis significantly influenced survival. CONCLUSIONS: This study suggests that KS is more aggressive and life threatening in female than in male patients. This peculiar clinical behavior may reflect an inherently more aggressive biology of KS in women, possibly mediated by the level of immunodeficiency.

AIDS-Related Opportunistic Infections↗
PubMed1999

HIV disease treatment in the era of HAART.

In the last three years basic science and clinical research have radically changed the therapeutical approach to HIV disease. Recent guidelines suggest that treatments to HIV disease should be early and aggressive, with the use of new potent antiretroviral drugs. This approach has been defined as HAART (highly active antiretroviral therapy). In this review we will discuss the main stages of antiretroviral therapy focusing on the acquisitions about results as well as problems of triple therapy.

Anti-HIV Agents↗
PubMed1998

Immune activation in HIV-infected African individuals. Italian-Ugandan AIDS cooperation program.

OBJECTIVE: Immune activation induced by chronic infections, dietary limitations, and poor hygienic conditions is suggested to be present in African HIV infection and is at the basis of the hypothesis that HIV infection in Africa could be prevalently associated with immunopathogenetic mechanisms. Very limited data are nevertheless available supporting this theory, and in particular no data are reported on functional and phenotypic analyses performed on fresh peripheral blood mononuclear cells (PBMC) of African HIV-infected patients living in Africa. DESIGN: Immunological and virological parameters were analysed in fresh PBMC of HIV-infected African and Italian patients with advanced HIV disease and comparable CD4 and CD8 counts, sex, and age. Both functional (antigen- and mitogen-stimulated cytokine production) and phenotypic (activation markers; markers preferentially expressed by T helper (Th) type 2 cells or by memory and naive cells) analyses were performed. Results were compared with those of HIV-seronegative African and Italian controls. HIV plasma viraemia was analysed by competitive polymerase chain reaction (PCR) and branched DNA techniques. RESULTS: (1) The production of mitogen-stimulated IFN-gamma and TNF-alpha as well as the production of env peptide-stimulated IFN-gamma, TNF-alpha, and IL-10 are increased in African HIV infection; (2) the expression of activation and Th2-associated markers is augmented in African HIV infection as is the memory/naive ratio; (3) mitogen-stimulated IFN-gamma and IL-10 production, as well as the expression of activation and Th2-associated markers and the memory/naive ratio, are augmented in African compared with Italian controls; and (4) plasma viraemia is reduced in African compared with Italian HIV-infected individuals. CONCLUSIONS: These results, which are the first to be reported on fresh material from African HIV-infected patients living in Africa, indicate that HIV disease is associated with an abnormal immune hyperactivation and may be accompanied in these patients by lower loads of virus, and show that such activation is present even in HIV-seronegative controls.

Adult↗
PubMed1998

Human T-lymphotropic virus type 2 (HTLV-2) provirus in circulating cells of the monocyte/macrophage lineage in patients dually infected with human immunodeficiency virus type 1 and HTLV-2 and having predominantly sensory polyneuropathy.

We investigated the presence of human T-lymphotropic virus type 2 (HTLV-2) DNA in the peripheral blood mononuclear cell subsets obtained from 18 patients coinfected with human immunodeficiency virus type 1 and HTLV-2, 6 of whom also had predominantly sensory polyneuropathy (PSP). HTLV-2 DNA and RNA were found in CD8- and CD19-positive cells, and, for patients with PSP, in CD14-positive cells as well. Furthermore, the patients with PSP had higher proviral loads than those without PSP.

AIDS-Related Opportunistic Infections↗
PubMed1996

Restricted tissue distribution of extralesional Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS patients with Kaposi's sarcoma.

Specific herpesvirus-like DNA sequences have been found in Kaposi's sarcoma (KS) lesions of AIDS patients, suggesting that a novel gamma herpesvirus, homologous to Epstein-Barr virus and herpesvirus saimiri, could be implicated in the pathogenesis of KS. To better understand the role of this putative etiological agent, named Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8), we investigated by the polymerase chain reaction (PCR) the presence of viral DNA sequences in various organs obtained at autopsy from seven AIDS patients with KS and six without KS. For each sample, to exclude positive results due to visceral KS dissemination, the presence of microscopic foci of KS cells was rules out by histology and CD34 immunohistochemistry on serial frozen sections immediately adjacent to those employed for DNA extraction. PCR and nested PCR were performed with primers specific for the HIV-8 330 Bam fragment originally described by Chang et al. (Science 1994;266:1865-1869). As quality control, the extracted DNA was amplified with primers for human beta-globin. All KS legions were HHV-8 positive. In addition, extralesional KSHV DNA sequences were detected in seven of seven lymphoid organs and in five of five prostate glands of KS patients. Normal skin was positive in three of five cases and bone marrow in two of three tested cases, all other tissues being negative by PCR and nested PCR. By contrast, no virus was detected in tissue samples of AIDS cases without KS. The restricted organ distribution here documented argues for a selective tissue tropism of HHV-8 in vivo in AIDS patients and suggests that in the infected host lymphoid organs and the prostate gland may represent privileged sites of viral latency and persistence.

Acquired Immunodeficiency Syndrome↗