[Show abstract][Hide abstract] ABSTRACT: Lipid abnormalities are among the most frequent treatment-limiting adverse events during HAART in HIV-infected individuals. Lipid disturbances have also been associated with hepatitis C virus (HCV) chronic infection in HIV-uninfected participants. HAART-induced lipid abnormalities may then have peculiar features in HIV-HCV co-infected individuals.
To estimate the prevalence and incidence rates of hypertriglyceridemia and hypercholesterolemia and to identify associated factors in a large clinic population of HIV patients after HAART has been initiated.
We performed a retrospective longitudinal follow-up study in a large cohort of HIV patients on their first HAART.
The clinical databases of two major clinical centers in Italy participating in the MASTER study were merged. Treatment-emerging metabolic disorders in patients on their first HAART regimen (PI-based or NNRTI-based) who were stable for at least 4 months were prospectively analyzed by baseline parameters, drug regimens, and viroimmunological outcome of therapy. Follow-up was continued for 24 months or until drug discontinuation, whichever came first.
Two hundred and eighty two (282) HIV-infected patients undergoing HAART (203 PI + 79 NNRTI; 65 including stavudine [d4T]) met inclusion criteria and were enrolled in the study from 1997 to 2001. Mean follow-up was 18.5 +/- 6.7 months. After HAART had been initiated, a statistically significant mean increase in total cholesterol over time was observed in comparison to baseline (p <.0001), without difference between treatment groups (PI vs. NNRTI, with or without d4T). In the univariate analysis, predictive factors for HAART-induced hypercholesterolemia were baseline total plasma cholesterol and triglycerides values and CD4+ cell count differential increase over time, while a negative correlation was found with zalcitabine-including regimens and baseline HCV seropositivity. At multivariate analysis, only high baseline total plasma cholesterol and triglycerides values retained their predictive value and baseline HCV seropositivity was significantly associated with lower increase in total cholesterol values under HAART, regardless of treatment groups (p <.001).
HCV co-infection is an independent factor preventing the emergence of treatment-limiting total cholesterol increase under any HAART regimen, possibly reflecting impaired total cholesterol synthesis in the liver or total cholesterol hypercatabolism. On the contrary, no HCV influence on triglycerides plasma levels was noted. Our data do not suggest any favoring role of specific treatment or drugs (PI and/or d4T) on total cholesterol and triglycerides increase under HAART.
HIV Clinical Trials 11/2002; 3(6):451-61. DOI:10.1310/W024-QC4T-NXU0-TKYT · 2.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several recent studies suggest that gammadelta T lymphocytes play an important role in immunity against Mycobacterium tuberculosis. However, the dynamics of these cells in the peripheral blood of patients with tuberculosis (TB) with and without HIV infection is not fully understood. A study was undertaken to evaluate the profile of the gammadelta T cell population in patients at the time the diagnosis of TB was established.
A cross sectional study was performed in consecutive TB patients from the Department of Infectious Diseases, Spedali Civili, Brescia. CD4+, CD8+ and Vdelta1 and Vdelta2 T cell counts were analysed. Lymphocyte surface membrane expression was evaluated with the FITC-TCRgammadelta, -Vdelta1, -Vdelta2 and PE-Vdelta1 monoclonal antibodies. Blood donors and HIV seropositive asymptomatic individuals acted as controls.
Seventy four TB patients were evaluated, 20 of whom (27%) were co-infected with HIV. HIV seronegative TB patients (n=54) had total gammadelta T cells and Vdelta1 subsets comparable to those in blood donors (n=39). However, the percentage with the Vdelta2 subset was significantly lower in patients with TB than in controls (median 1.5 v 2.1; p=0.05). Responsiveness to PPD was not associated with predominance of a specific gammadelta T cell subset. HIV seropositive individuals had a decreased percentage of circulating Vdelta2 cells at a level similar to that in HIV seronegative TB patients, regardless of the presence of active TB.
HIV seronegative TB patients and HIV infected individuals (with or without active TB) have a reduced number of circulating Vdelta2 T cells compared with healthy individuals. Whether TB and HIV infection share a common mechanism causing Vdelta2 T cell depletion still needs to be established.
[Show abstract][Hide abstract] ABSTRACT: Background: Several recent studies suggest that γδ T lymphocytes play an important role in immunity against Mycobacterium tuberculosis. However, the dynamics of these cells in the peripheral blood of patients with tuberculosis (TB) with and without HIV infection is not fully understood. A study was undertaken to evaluate the profile of the γδ T cell population in patients at the time the diagnosis of TB was established.Methods: A cross sectional study was performed in consecutive TB patients from the Department of Infectious Diseases, Spedali Civili, Brescia. CD4+, CD8+ and Vδ1 and Vδ2 T cell counts were analysed. Lymphocyte surface membrane expression was evaluated with the FITC-TCRγδ, -Vδ1, -Vδ2 and PE-Vδ1 monoclonal antibodies. Blood donors and HIV seropositive asymptomatic individuals acted as controls.Results: Seventy four TB patients were evaluated, 20 of whom (27%) were co-infected with HIV. HIV seronegative TB patients (n=54) had total γδ T cells and Vδ1 subsets comparable to those in blood donors (n=39). However, the percentage with the Vδ2 subset was significantly lower in patients with TB than in controls (median 1.5 v 2.1; p=0.05). Responsiveness to PPD was not associated with predominance of a specific γδ T cell subset. HIV seropositive individuals had a decreased percentage of circulating Vδ2 cells at a level similar to that in HIV seronegative TB patients, regardless of the presence of active TB.Conclusions: HIV seronegative TB patients and HIV infected individuals (with or without active TB) have a reduced number of circulating Vδ2 T cells compared with healthy individuals. Whether TB and HIV infection share a common mechanism causing Vδ2 T cell depletion still needs to be established.
[Show abstract][Hide abstract] ABSTRACT: Effectiveness of combination therapy with standard interferon alpha doses and ribavirin is far from being demonstrated in patients with hepatitis C non responders to interferon alpha monotherapy. Recent kinetic studies revealed that these doses may be suboptimal.
To find the criteria for optimisation of the interferon dose, to be used in combination with ribavirin in patients with hepatitis C non responders to interferon alpha monotherapy.
Sixty-three patients enrolled in a pilot controlled trial were treated for 6 months with ribavirin ([1000-1200 mg daily) and were randomised to concurrently receive interferon alpha 2b for 6 months at: 3 Million Units thrice weekly [group A (21 patients)], 5 MU thrice weekly [group B (21 patients)] and 5 million units daily [group C (21 patients)].
A sustained virological response was observed in: 1 patient from group A (5%), 2 patients from group B (9%) and 8 patients from group C (38%; p=0.02 vs group A; p=0.03 vs group B). Side-effects were not significantly different between the 3 groups. Multivariate analysis showed that infection by hepatitis C virus genotypes 2 or 3 and interferon alpha dosage of 5 million units daily were independent predictors of sustained response.
These results suggest that higher interferon doses administered daily in combination with ribavirin could be more effective in those patients with hepatitis C who had not responded to interferon alone.
[Show abstract][Hide abstract] ABSTRACT: The authors present the AIDS cases (CDC '93) observed in Brescia from 1983 to 1994. They observed 1189 subjects (M 84%, F 16%) with a mean age of 32.7 years (intra-venous drug users 75.1%, heterosexuals 14%, homosexuals 9.6%). The mean survival observed was 56.7 weeks from the diagnosis of AIDS (mortality per year 78%). The most frequent AIDS-defining events were Visceral Candidiasis, P. carinii Pneumonia (PCP) and Neurotoxoplasmosis, while the longest and shortest mean survival was for Kaposi's Sarcoma (89 weeks) and Wasting Syndrome (8.4). The mean value of CD4+ lymphocyte counts on AIDS diagnosis was 72.6/microl (1166 cases) and the highest and lowest were in non-Hodgkin's Lymphoma (NHL; 147.6/microl) and Cryptosporidiosis (18.8/microl). Antiretroviral therapy had been given for at least a month in 41.4% subjects (mean treatment duration of 74.8 weeks). The Cox model has demonstrated the favourable effect on survival of high CD4+ lymphocyte counts on diagnosis, antiretroviral therapy, the diagnosis of Tuberculosis (TBC) and PCP as initial markers and the diagnosis of TBC, PCP or Cytomegalovirus infection (CMV) during the entire clinical evolution. Moreover, the unfavourable effect of high age, diagnosis of Progressive Multifocal Leucoencephalopathy (PML), Wasting Syndrome and NHL as initial markers and diagnosis of PML or NHL in any moment of the disease has been demonstrated.
European Journal of Epidemiology 10/1999; 15(8):691-8. DOI:10.1023/A:1007676625117 · 5.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatitis A virus (HAV) circulation in a given area is closely related to socioeconomic standards. Following the improvement of living conditions, HAV seroprevalence rates in the population have decreased steadily during the last decades in many Western European countries, including Italy, thereby leading to a shift of risk of disease towards older age groups. Since the severity of the disease closely parallels age, a higher incidence of symptomatic cases in adults is now reported in Europe and the United States, being travel-related to a large extent. Intrafamilial person-to-person spread is also an important source of infection and transmission from children to parents may occur due to the lack of immunity in the general population. In the last two decades, Italy has been the destination of an increasing number of migrants from developing countries, where HAV is highly endemic. Furthermore, international adoption programmes cause pediatric populations from HAV endemic countries to increase in low endemic areas, possibly leading to secondary cases in close contacts.7 The aim of this paper is to report the epidemic HAV outbreak which occurred among the voluntary nursing staff of a pediatric Rwandan refugee community hosted in a village of the Brescia Province, in northern Italy.
Journal of Travel Medicine 10/1999; 6(3):204-6. DOI:10.1111/j.1708-8305.1999.tb00859.x · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Portal lymphadenopathy is frequently found in inflammatory liver diseases. However, the mechanisms underlying portal lymphadenopathy are unknown.
To evaluate the prevalence of portal lymphadenopathy in patients with serum anti-hepatitis C Virus antibody reactivity and its relationship to clinical parameters.
The presence of portal lymphadenopathy was evaluated by upper abdominal Ultrasound by the same examiner in 114 patients with anti-hepatitis C Virus reactivity: 56 patients with normal liver enzyme activity and 58 randomly selected patients with increased liver enzyme activity undergoing liver biopsy. Laboratory tests were then performed in all patients the following day.
Portal lymph nodes were found in a significantly higher percentage of patients with increased liver enzymes (74%) than in patients with persistently normal liver enzymes (29%: p < 0.01). Aminotransferases, gamma glutamyl transpeptidase levels and the percentage of patients with HCVRNA in serum and histological scores for piecemeal and lobular necrosis were significantly higher in patients showing hepatic lymph nodes. Multivariate analysis showed that only alanine aminotransferase and lobular necrosis were independently related to the presence of hepatic lymph nodes. A significant correlation was found between lymph node size, aminotransferase activity and lobular necrosis.
Ultrasound-proven portal lymph node enlargement is an indirect sign of hepatocellular damage in patients with positive serum anti-hepatitis C Virus antibodies.
Italian journal of gastroenterology and hepatology 06/1999; 31(4):295-300.
[Show abstract][Hide abstract] ABSTRACT: We considered the HIV population of our area, comparing demographic characteristics between 2 consecutive 6-year periods to assess the current patterns of HIV transmission. All HIV-positive patients referred to our hospital from January 1985 to December 1996 were included in the study and were classified into 2 periods: A (January 1985 to December 1990) and B (anuary 1991 to December 1996). The variables analysed were: sex, age at first visit, HIV risk category. A total of 4284 HIV subjects were observed, 2306 in period A vs 1978 in period B (P=ns). Males were 76.3% vs 75.2% (P=ns). Mean age for males was 27.4 vs 32.4 years (P < 0.001) and for females 25.4 vs 30.1 years (P < 0.001). Intravenous drug users (IVDUs) were 88.4% vs 65.4% (P < 0.001), 'heterosexuals' 14.3% vs 24.8% (P < 0.001), 'men who have sex with men' 2.4% vs 4.8% (P < 0.001). Mean age by the main risk groups was: IVDUs 25.9 vs 29.7 years (P < 0.001); heterosexuals 30.4 vs 36 years (P=0.007); 'men who have sex with men' 35 vs 35 years. In conclusion, our study confirms the emerging role of heterosexuals in the current HIV epidemic. People older than teenagers seem to have misperceived their own risk of HIV infection, given the increase in the mean age occurred in the most recent years. This trend suggests the need for prevention strategies focusing more on heterosexual transmission and older people.
International Journal of STD & AIDS 12/1998; 9(12):740-3. DOI:10.1258/0956462981921495 · 1.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The T cell repertoires were characterized for CD4+ and CD4 lymphocytes derived from 2 patients with acute human immunodeficiency virus (HIV) infection and from 25 HIV-seronegative persons at high risk for acquiring HIV. Oligoclonal expansions of CD4 cells were detected in the HIV-infected patients and in 2 of 3 uninfected high-risk subjects with a reduced number of CD4+ lymphocytes. Furthermore, nucleotide sequencing revealed that some of the T cell receptor (TCR) beta variable segments (TCRBV), which were highly selected in the high-risk subjects, shared closely related junctional sequences, with the TCRBV predominantly expanded in the HIV-infected patients. Since the likelihood that these similarities occurred by chance is extremely low, these data provide direct molecular evidence in support of several cellular and serologic studies suggesting that some persons remain uninfected despite exposure to HIV.
The Journal of Infectious Diseases 03/1997; 175(2):272-82. DOI:10.1093/infdis/175.2.272 · 5.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mycoplasma have been suggested as co-factors in the pathogenesis of acquired immune deficiency syndrome (AIDS). The prevalence of urethral infection by Mycoplasma genitalium was determined by polymerase chain reaction (PCR) with urethral swabs from 35 HIV-infected patients at different stages of the disease (all of them were heterosexual men). M genitalium was detected in 2 out of 19 non-AIDS (stage A and B) patients and in a similar proportion (1 out of 14; 7.1%) of samples from healthy individuals. A dramatic increase in the frequency of M. genitalium detection was observed in samples of AIDS (stage C) patients. In fact, 9 out of 16 (56.2%) specimens tested positive by PCR. We found no association in AIDS patients between M. genitalium infection and CD4 count, Human Immunodeficiency Virus (HIV) p24 antigenemia or opportunistic infection.
The New Microbiologica: official journal of the Italian Society for Medical Virology (SIVIM) 08/1996; 19(3):203-9. · 1.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report clinical and microbiological features and response to treatment in HIV patients with Rhodococcus equi infection.
Inpatients admitted to two Infectious Diseases Departments in a community-based hospital.
A total of 12 HIV-positive patients with R. equi infection.
Clinical status, radiological finding, microbiological, haematochemical and immunological tests, and response to treatment.
Twelve patients (11 men, six injecting drug users) were diagnosed with R. equi infection. Fever and cough were the principal clinical signs on presentation. Mean CD4+ count at the time of diagnosis was 47.67 x 10(6)/l (SD, 49.2 x 10(6)/l). In 58.3% of the cases the diagnosis of R. equi infection followed the appearance of an AIDS-defining illness. The most frequent radiological findings were cavitary lesions (41.7%) and lung consolidation (33.3%). In 83% of cases, R. equi was isolated from blood and in 33.3% cases from sputum. Test of chemosensitivity showed sensitivity to vancomycin (100%), teicoplanin (100%), ceftriaxone (80%), erythromycin (71%) and ciprofloxacin (66%). Clinical response alone with the disappearance of the presenting signs was observed in nine of the 12 cases (75%); complete response was observed in two cases. Seven patients died with a mortality rate of 58.3% and a mean survival of 5.75 months (SD, 6.48 x 10(6)/l).
R. equi should be considered in the differential diagnosis of pulmonary of disseminated infections in patients with HIV infection. Blood culture may be the most sensitive means of diagnosis. Other studies are needed to determine the most effective choice and duration of antibiotic therapy.
AIDS 05/1996; 10(4):359-62. DOI:10.1097/00002030-199604000-00002 · 6.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A retrospective investigation was made to compare the occupational risk of tuberculosis in personnel assisting human immunodeficiency virus (HIV)-infected and uninfected subjects with active tuberculosis.
We retrospectively reviewed 6 years of hospital activity in 3 units where HIV-infected patients with tuberculosis are hospitalized and in 2 units where non-HIV-infected tuberculosis patients are hospitalized. The risk of occupational tuberculosis in healthcare workers who assisted HIV-infected and non-HIV-infected patients with tuberculosis was investigated.
The risk of occupational tuberculosis in healthcare workers was studied by considering the numbers of potential source cases (hospitalized patients with tuberculosis) in the two conditions investigated (HIV-positive and HIV-negative). Both potential source cases and cases of tuberculosis in healthcare workers had to be microbiologically proven in order to be considered.
Seven cases of tuberculosis occurred in persons who cared for 85 HIV-infected subjects with tuberculosis, while only 2 cases occurred in staff members who took care of 1,079 HIV-negative tuberculosis patients over the same period (relative risk = 44.4; 95% confidence interval = 8.5-438).
Tuberculosis seems no longer to be a neglectable risk in healthcare workers assisting patients with HIV infection. Further study is urgently needed to see whether such unexpectedly high dissemination of tuberculosis also is demonstrable in the community.
Infection Control and Hospital Epidemiology 03/1993; 14(2):67-72. DOI:10.2307/30147163 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Light and Electron Microscope aspects of a colonic Cryptosporidiosis in a H.I.V. patient are reported. The authors stresses the importance of Endoscopic biopsies and Electron Microscopic studies in confirming the microbiologic stool examination for oocysts of the parasite. In particular, by an histological point of view, there are no specific findings indicative for Cryptosporidium infection, apart the identification of the parasite forms with PAS, Giemsa and Grocott stains. Electron Microscopy reveals in this case only the presence of Macrogametocyte.
[Show abstract][Hide abstract] ABSTRACT: We evaluated 95 HIV seropositive drug-addicts during a follow-up period of one year. The patients were classified and reclassified at each visit, according to the criteria proposed by the Centers for Disease Control (CDC) in 1986. At the first visit the patients were classified as follows: 70 in IIa-IIIa, 23 in IIb-IIIb and 2 in group IV. a and b indicate the absence or the presence of immunological and/or hematological alterations. 1 out of 70 IIa-IIIa patients versus 8 out of 23 IIb-IIIb patients developed AIDS in one year (p less than 0.001). Only one patient belonging to IIa-IIIa groups at the first visit progressed to AIDS in one year. This patient was reclassified in subgroup b after six months. No differences were noted among patients classified in IIb (5 patients) and IIIb (4 patients) who progressed to AIDS. Taken together these data indicate that the belonging to b subgroup is a risk factor for developing AIDS and the passage through a b subgroup (II or III) is a necessary step before the appearance of clinical manifestations of AIDS.
[Show abstract][Hide abstract] ABSTRACT: Cefotaxime concentrations in the cerebrospinal fluid and serum were determined in patients with purulent meningitis by means of a simple, rapid and reproducible method in agar medium. The CSF concentrations of cefotaxime fluctuated around 4 mg/l. The pharmacokinetics of the antibiotic in relation to the integrity of the blood-brain barrier was studied by means of an assay of the albumin and IgG present in the cerebrospinal fluid and in the serum.