PubMed Health⌕ Search

Biomedical subjects

Massimo Galli

Publications and source records attributed to Massimo Galli.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2004

Immunomodulation induced by tucaresol in HIV infection: results of a 16 week pilot Phase I/II trial.

OBJECTIVE: Immune reconstitution in highly active antiretroviral therapy (HAART)-treated individuals is incomplete and immunomodulatory compounds are needed to improve the outcome of HIV therapy. In a Phase I/II clinical trial performed on HIV-positive patients we analysed the safety and immunomodulating effects of tucaresol, a novel compound that has previously been described tn enhance cell-mediated immune responses. PATIENTS AND METHODS: Sixteen weeks pulse dose escalation protocol. Four groups of HIV-positive patients were enrolled: group A (n=6): HAART, CD4+ 300-500 cells/microl, HIV RNA <80 copies/ml; group B (n=6): HAART-naive, CD4+ <500 cells/microl, HIV RNA >10 000 copies/ml; group C (n=3): HAART-naive, CD4+ >500 cells/microl, HIV RNA <10000 copies/ml; and group D (n=6): HAART, CD4+ <200cells/microl, HIV RNA <80 copies/ml. Tucaresol was added to HAART in group A and D patients; group B patients started tucaresol with HAART, group C patients received tucaresol alone. Clinical and immunological analyses were performed at different time points. RESULTS: Tucaresol-related serious adverse events were observed in the first week of therapy in 2/21 patients who were viraemic when commencing treatment, but did not occur in patients on stable HAART. Tucaresol did not affect HIV viraemia whereas increases in CD4+ percentages, mainly supported by naive CD4+ cells, were observed. CD8+/28-/45RA+ cells and HIV-specific CD8+ IFNgamma- and perforin-producing cells improved whereas IL-10 mRNA diminished in tucaresol-treated patients. The effects were greater with 25 mg given every other day for 1 week. CONCLUSION: In HAART-receiving patients with proper virus suppression, tucaresol was not associated with serious adverse events and resulted in qualitative and quantitative stimulation of HIV-specific cytotoxic T lymphocyte activity and generation of naive T cells. These data may support further exploration of tucaresol use in reconstitution of immune system parameters in HIV patients with proper virus suppression while on HAART.

Adult↗
PubMed2003

Gender differences in antiretroviral drug-related adipose tissue alterations. Women are at higher risk than men and develop particular lipodystrophy patterns.

Adipose tissue alterations (ATAs) were clinically assessed in 2258 HIV-1-infected outpatients consecutively observed in 6 Italian clinical centers and were found to be present in 29.5% of the men and 41.9% of the women. A logistic regression model including age, HIV disease Centers for Disease Control stage, CD4 cell counts, HIV RNA load, the duration of antiretroviral therapy, the number of drugs taken, and the use of d4T showed that men had a 0.47 adjusted risk of presenting with ATAs (95% CI: 0.38-0.58, P < 0.0001). The risks of having ATAs (except circumscribed lipomas) in any body region, presenting with fat accumulation, or being affected by combined forms of ATA were also lower in men, whereas the risk of developing pure lipoatrophy was similar in the 2 genders. Our results indicate that women are at higher risk of developing antiretroviral treatment-related ATAs and show a particular and complex ATA pattern.

Adipose Tissue↗
PubMed2003

Low expression of inhibitory natural killer receptors in CD8 cytotoxic T lymphocytes in long-term non-progressor HIV-1-infected patients.

We investigated whether a different pattern of HLA-specific inhibitory natural killer receptor (iNKR) expression on peripheral blood mononuclear cells (PBMC) of long-term non-progressor (LTNP) patients explained their benign course of HIV-1 infection. The surface expression of p70, p140 and CD94/NKG2A in their CD3+CD8+ PBMC was comparable to that of uninfected donors. The lack of iNKR-mediated functional inhibition of HIV-1-specific cytotoxic T lymphocytes in vitro could provide an additional mechanism for the efficient control of virus spread in LTNP patients.

Adult↗
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↗
PubMed2003

Increased mitochondrial DNA content in peripheral blood lymphocytes from HIV-infected patients with lipodystrophy.

We have evaluated mitochondrial (mt) DNA content in CD4 and CD8 peripheral blood lymphocytes (PBLs) from HIV-infected patients taking highly active antiretroviral therapy (HAART) who display different types of adipose tissue alterations. A cross-sectional study was performed in a total of 23 patients with lipodystrophy (LD): nine patients with fat accumulation, six patients with fat loss, eight patients with combined form, who were compared to 11 individuals infected by HIV without LD (HIV-positive) and 10 seronegative controls (CTRL). PBLs were obtained by standard methods, that is, gradient density centrifugation on Ficoll, and CD4 or CD8 cells were positively isolated by magnetic sorting to eliminate the contamination of platelets. mtDNA content was then measured by an original assay based upon real-time PCR. mtDNA content was significantly increased in CD4 T cells from patients with LD, while no differences were present between CD4 and CD8 cells from HIV-positive and CTRL individuals. Nor were any differences found when comparing LD or HIV-positive patients treated with stavudine or zidovudine, or taking D-drugs or non D-drugs. Patients with fat accumulation had significantly higher mtDNA content compared to HIV-positive and CTRL, this phenomenon regarding both CD4 and CD8 PBLs. Considering all HIV-positive patients (including LD), mtDNA content showed a significant, positive correlation with cholesterolaemia but not with triglyceridaemia and glycaemia. Relatively high mtDNA content in LD patients, as well as the correlation between mtDNA content and cholesterol in all HIV-positive subjects, suggest the involvement of mitochondria in such a pathology. However, further studies are needed to confirm these initial observations and ascertain whether the quantification of mtDNA in PBL is a useful and reliable marker to investigate and monitor HAART-related changes in fat distribution.

Adipose Tissue↗
PubMed2003

Correlates of risk of adipose tissue alterations and their modifications over time in HIV-1-infected women treated with antiretroviral therapy.

OBJECTIVE: To assess the correlates of risk of the different types of lipodystrophy and their modifications over time in a cohort of HIV-positive women receiving antiretroviral therapy (ART). METHODS: A consecutive series of HIV-infected women receiving ART was prospectively enrolled between 1 and 31 March 1998, and followed up for 2 years. Adipose tissue alterations (ATAs) and their variations over time were assessed by means of clinical observation and anthropometric measurements, and logistic regression analysis was used to describe the associated risk factors identified by univariate and multivariate analyses. RESULTS: One-hundred-and-seventeen of the 212 women (55.2%) developed ATAs during the 24 months of follow-up. Central adiposity was observed in 95 patients and peripheral lipoatrophy in 91, with 21 patients (9.9%) showing pure lipoatrophy, 26 (12.3%) pure fat accumulation and 70 (33%) combined forms. Only six of the 223 regional adipose tissue alterations identified in 74 patients during the first 12 months of the study had disappeared by month 24. Of the 43 patients who developed breast enlargement during the first 12 months, 11 (25.6%) showed a decrease in breast size during the second year of follow-up that was unrelated to changes in therapy or therapeutic success. The development of ATAs during the first 12 months of follow-up independently correlated with protease inhibitor (PI) use (OR 2.81, P=0.002) but, by the end of the second year of follow-up, the only factor significantly related to the development of ATAs was the overall duration of ART (OR 1.85, P=0.041). The use of PI significantly increased the risk of developing central adiposity during the first 12 months of the study (OR 2.27, P=0.002), whereas the only variable significantly influencing the risk at month 24 was HIV-infection due to intravenous drug use, which proved to be protective (OR 0.53, P=0.043). During the first 12 months of follow-up, the development of peripheral lipoatrophy was significantly associated with stavudine (OR 2.19, P=0.037) and PI use at enrolment (OR 2.27, P=0.023). At the end of the study, the variables associated with peripheral lipoatrophy were stavudine use at enrolment (OR 2.82, P=0.002), ART exposure for >1000 days at enrolment (OR 2.32, P=0.007), a CD4 cell count of >200/microl at enrolment (OR 2.89, P=0.002) and an age of >28 years (OR 1.91, P=0.036). The only factor significantly associated with an increased risk of breast enlargement during the first 12 months of follow-up was PI use (adjusted OR 2.51; 95% CI: 1.16-5.46, P=0.02); however, at month 24, none of the tested variables was associated with a significantly increased risk of this ATA. CONCLUSIONS: ATAs (particularly central adiposity) are frequent in women treated with ART, and the different forms have different correlates of risk. Once they have become clinically evident, they generally tend to remain or worsen, and improve in only a small minority of cases. The considerable variations in adipomasty over time are apparently unrelated to changes in ART.

Adipose Tissue↗
PubMed2002

Relationship between HAART adherence and adipose tissue alterations.

Adipose tissue alterations (ATA), which are common among persons treated with highly active antiretroviral therapy (HAART), can have substantial psychologic repercussions, with a subsequent negative impact on the patient's quality of life and on HAART adherence. However, the cross-sectional nature of the studies precludes establishing the direction and causality of the relationship. The authors evaluated the longitudinal relationship between ATA and adherence to HAART. The analysis included all participants in the AdICoNA and the LipolCoNA substudies of the Italian Cohort Naive Antiretrovirals (ICoNA). Adherence was assessed using a 16-item self-administered questionnaire, which also included a question on self-perceived fat accumulation experienced during the past 4 weeks. ATA was diagnosed by physicians at enrollment and evaluated every 6 months thereafter. There were 207 patients, with a median age of 35 years; 73% were men; and 34% acquired HIV through injection drug use. At baseline, nonadherence was reported by 63% of participants, and ATA was self-perceived by 15% and clinically diagnosed in 25%. Using Cox regression analysis, patients with good adherence at baseline were more likely to develop ATA (RH = 2.58; 95% CI, 1.09-6.11) and developed it sooner. Self-perceived ATA at baseline was independently related to subsequent nonadherence (OR, 4.67; 95% CI, 1.01-22.4), but clinically diagnosed ATA was not (OR, 0.77; 95% CI, 0.37-1.61). Patients' adherence to HAART is a dynamic process that interacts with ATA. Better adherence is associated with a higher risk of subsequent occurrence of ATA, while patient-perceived onset of morphologic alterations can reduce adherence to antiretroviral therapy.

Adipose Tissue↗
PubMed2002

Thrombotic microangiopathy in patients with acquired immunodeficiency syndrome before and during the era of introduction of highly active antiretroviral therapy.

The incidence of thrombotic microangiopathy (TMA) was retrospectively evaluated in a cohort of 1223 patients with acquired immunodeficiency syndrome (AIDS) who were observed from January 1985 through December 1996 (before the era of highly active antiretroviral therapy [HAART]), and the incidence was prospectively assessed for 347 patients with AIDS during the period of January 1997 through December 2000 (during the HAART era). Seventeen cases were reported in the former cohort (1.4%). The increased risk of developing TMA was statistically significant in patients with cryptosporidiosis or AIDS-related cancer but not in those with other diseases. In the 1997-2000 cohort, no cases were observed during follow-up. TMA is associated with conditions observed in the advanced phases of human immunodeficiency virus infection. The disappearance of TMA during the HAART era may be explained by the lower percentage of patients with long-lasting CD4+ T cell depletion, advanced AIDS, or cryptosporidiosis or who have undergone multiple courses of chemotherapy for treatment of cancer.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Increased risk of developing peripheral neuropathy in patients coinfected with HIV-1 and HTLV-2.

One thousand one hundred fifty-two HIV-1-positive patients were screened for HTLV-2 infection, and the AIDS-free coinfected individuals were consecutively included in a longitudinal study with the aim of investigating the role of HTLV-2 in the progression to AIDS and the development of specific neurologic diseases. Two matched HIV-1-positive/HTLV-2-negative controls for each coinfected individual were also enrolled in the study. HTLV-2 infection was found in 95 (8.2%) of the HIV-1-positive patients, 30 of whom were followed up for a median of 28.5 months. No significant differences were observed between them and the patients infected with HIV-1 alone in terms of the rate of decline in CD4 cell counts, progression to AIDS, or AIDS mortality, but they had an increased risk of developing peripheral neuropathy (hazard ratio, 3.3; 95% confidence interval, 1.3-8.0; p =.009). One coinfected patient developed myelopathy during the follow-up. In the second part of the study, aimed at preliminarily assessing the effect of highly active antiretroviral therapy (HAART) on the incidence of peripheral neuropathy, we extended our observations to two groups of coinfected and singly infected individuals receiving HAART. An 80% decrease in incidence of peripheral neuropathy was observed among both groups without any significant difference between them. These results support the hypothesis that HTLV-2 plays a role in the development of neurologic abnormalities in HIV-1-infected patients and suggest that the immune reconstitution due to HAART may limit the activity of HTLV-2 as an opportunistic agent.

Acquired Immunodeficiency Syndrome↗
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↗