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Biomedical subjects

T Bini

Publications and source records attributed to T Bini.

At least 19 recordsLinked to original sources

Nephrolithiasis and hydronephrosis in an HIV-infected man receiving tenofovir.

The use of tenofovir as part of a HAART regimen has been widely used in HIV-multi-experienced-patients because of its favourable resistance profile. Tenofovir is mainly eliminated by the kidneys and renal toxicity should be carefully monitored. We describe here the case of an HIV-infected patient, without a prior history of renal failure who developed nephrolithiasis and hydronephrosis after starting a tenofovir-containing HAART regimen.

Adenine↗

Lopinavir/ritonavir treatment in HIV antiretroviral-experienced patients: evaluation of risk factors for liver enzyme elevation.

OBJECTIVES: To evaluate the risk factors for lopinavir/ritonavir (LPV/r)-related liver enzyme elevation (LEE) in HIV antiretroviral-experienced patients. METHODS: An open prospective observational study was carried out to analyse the incidence and time of LEE development during LPV/r treatment, and to determine whether LEE development was correlated with epidemiological, clinical and biochemical data, immune and virological profiles, concomitant hepatic diseases, antiretroviral therapy, or histological and ultrasonography liver examination results. A diagnosis of LEE was considered when LEE symptoms occurred after LPV/r introduction and was confirmed by a second control within 2 weeks. RESULTS: A total of 782 HIV-positive outpatients have been enrolled in six different Infectious Diseases Departments in Northern Italy since August 2000. Of these patients, 71 (9.1%) developed LEE within 115+/-85 days (mean+/-standard deviation); 13 of these subjects discontinued LPV/r and four were hospitalized. Of the patients with LEE, 74.6% and 25.4% had grade 2 and > or =3 toxicity, respectively. No correlation between LEE and sex, baseline CD4 cell count, viral load, HIV stage, triglyceride values, histological and ultrasonography liver examination results, nevirapine use, or increase in CD4 cell count was observed. Higher baseline alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) values (P < 0.0001 and P=0.004, respectively), younger age (P=0.008), previous hepatitis B virus (HBV) infection (P=0.012), efavirenz use (P=0.04), and hepatitis C virus (HCV) and/or HBV coinfection (P < 0.0001, relative risk 4.78) were significantly related to LEE. No correlations between LEE and the same risk factors as investigated in the whole study population were found in subgroups of patients with HCV and/or HBV infection. CONCLUSIONS: HCV and HBV testing and measurement of baseline ALT values are essential for screening subjects at risk of LEE before starting LPV/r. Strict monitoring of clinical and biochemical parameters should be performed in these patients.

Adult↗

Declining incidence of AIDS and increasing prevalence of AIDS presenters among AIDS patients in Italy.

Presented here are the results of a cohort study conducted on 3,483 consecutive HIV/AIDS patients between January 1993 and December 2000 to determine trends in AIDS incidence and presentation. The incidence of AIDS was calculated in the general population and examined further according to gender, age (< or = or >49 years), and heterosexual behaviour as a risk factor for HIV. Multivariate analysis was used to identify variables associated with AIDS presenters (defined as patients diagnosed with AIDS within 1 month of the first HIV-positive test). The numbers of patients with AIDS classified as (i) AIDS presenters, (ii) known HIV-positive patients on antiretroviral treatment, and (iii) known HIV-positive patients not receiving antiretroviral treatment were calculated. The overall incidence of AIDS decreased over time, mainly due to the lower number of patients on antiretroviral treatment developing AIDS. Factors associated with a higher risk of being an AIDS presenter were male gender and year of HIV diagnosis. Among patients with AIDS, the proportion of AIDS presenters increased from 13.8% prior to 1997 (when protease inhibitors were introduced in Italy) to 32.5% after 1997. Variables predictive of being an AIDS presenter were male gender, age at diagnosis, and AIDS diagnosis in the years 1997-2000. Heterosexuals had a higher risk of being AIDS presenters and a lower risk of being HIV-positive and not receiving antiretroviral treatment than intravenous drug users. In Italy, AIDS occurs mainly in subjects unaware of their HIV status (especially males, the elderly, and those infected heterosexually) or in patients refusing antiretroviral therapy (mainly intravenous drug users who do not refer to specialised centres).

AIDS-Related Opportunistic Infections↗

Predictive role of the three-month CD4 cell count in the long-term clinical outcome of the first HAART regimen.

The aim was to evaluate whether the three-month CD4 cell counts are a reliable predictor of the long-term clinical outcome of HAART-treated patients, by an observational study of 585 patients initiating HAART in a clinical setting. Clinical failure was defined as the occurrence of new or recurrent AIDS-defining events or death, and was analysed by means of intention-to-treat, univariate and multivariate analyses. An adjusted Cox regression model was used to evaluate the effect of three-month CD4+ counts on clinical outcome. Clinical failure occurred in 65 patients (11.1%) during a median follow-up of 31 months (1-65) as a result of new AIDS-defining events (ADEs) in 48 patients, ADE recurrence in six, and death in 11. The mean (median; range) CD4+ counts were 156/microL (155; 4--529) in patients with and 362/microL (326; 18--1162) in patients without clinical failure (P < .0001). Moreover, the proportion of patients with mean CD4+ counts < 200 microL was higher in those experiencing subsequent clinical failure (chi2: 41.11; P< .00001). Multivariate analysis showed that baseline CD4+ counts < 50 microL, HIV-RNA > 100,000 copies/mL and AIDS at baseline predicted failure; after adjusting for three-month CD4+ counts, this marker was the only one independently associated with clinical failure (HR 2.93; 95% Cl: 1.16--7.38). The three-month immunologic response is a reliable predictor of long-term clinical outcome.

Acquired Immunodeficiency Syndrome↗

Outcome of a second-line protease inhibitor-containing regimen in patients failing or intolerant of a first highly active antiretroviral therapy.

The outcome of second-line protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) was investigated in 263 patients who were failed by (n = 148) or intolerant of (n = 115) a first HAART regimen. The endpoints were virologic failure (decline in HIV RNA < 1 log10 copies/ml after > or = 2 months) and discontinuation due to intolerance/toxicity. During a median follow-up of 483 days (33-1087 days), 154 patients (59%) discontinued the second regimen, 86 (33%) because of intolerance/toxicity; another 135 patients (51.3%) showed virologic failure. Independent factors associated with virologic failure (Cox's model) were 7 to 12 months of first HAART (hazard ratio [HR] 1.70 versus < or = 6 months: 95% confidence interval [CI], 1.08-2.70) and gender (HR 1.58 males versus females: 95% CI, 1.04-2.30); the negatively associated factors were advanced age (HR 0.61 > 34 years versus < or = 34 years: 95% CI, 0.42-0.88), a saquinavir-containing first HAART (HR 0.57 versus indinavir: 95% CI, 0.34-0.93) and change due to intolerance/toxicity (HR 0.58 versus failure: 95% CI, 0.35-0.98). The independent variables predictive of discontinuation due to intolerance/toxicity were the reason for switching (HR 1.79 intolerance versus failure: 95% CI, 1.02-3.16) and the first protease inhibitor (PI) regimen (HR 0.42 ritonavir versus indinavir: 95% CI, 0.22-0.80). Given that patients who are failed by a first regimen are at high risk of having rescue therapy fail as well, second-line regimens including therapies directed by testing of drug resistance patterns of clinical viral isolates are warranted. Patients experiencing toxicity due to a first PI-containing regimen are at risk of toxicity to other PIs and should be addressed to PI-sparing HAART.

Acquired Immunodeficiency Syndrome↗

Body habitus alterations in HIV-infected women treated with combined antiretroviral therapy.

Fat distribution alterations are among the most frequent and unexpected side effects of combined antiretroviral therapy. They may occur in patients receiving protease inhibitor-containing regimens and those treated with combinations of only nucleoside reverse transcriptase inhibitors. The broad spectrum of body fat alterations, which are variably associated with metabolic abnormalities, raises the question as to whether they represent different components of the same syndrome or are manifestations of different pathogenetic mechanisms. Recent clinical evidence is consistent with a higher risk of developing body fat alterations in females. We here report three different aspects of body habitus changes in women treated with various antiretroviral regimens and describe their short-term follow-up. We also discuss the possible pathogenetic implications and the role of different drug classes according to present knowledge.

Adult↗

CD4 cell counts at the third month of HAART may predict clinical failure.

OBJECTIVE: To evaluate the influence of immunological and virological markers on clinical outcome in patients receiving their first highly active antiretroviral therapy (HAART) regimen. DESIGN AND METHODS: Observational study of 585 patients initiating HAART in a clinical setting. Clinical failure was defined as the occurrence of new or recurrent AIDS-defining events or death, and was analysed by means of intention-to-treat, univariate and multivariate analyses. An adjusted Cox regression model was used to evaluate the effect of 3-month CD4 cell counts on clinical outcome. RESULTS: Clinical failure occurred in 55 patients (9.4%) during a median follow-up of 483 days (range 33-1334 days): 45 new AIDS-defining events (ADEs) in 38, ADE recurrence in six, and death in 11. Twenty-four of the 45 new ADEs (53.4%) occurred during the first 3 months of HAART, and 11 of 45 (24.4%) in the presence of CD4 cell counts > 200 x 10(6) cells/l. The mean (median, range) CD4 counts were 144 x 10(6) cells/l (128, 4-529) in patients with and 322 x 10(6) cells/l (288, 14-1162) in patients without clinical failure (P < 0.0001). Moreover, the proportion of patients with mean CD4 cell counts < 200 x 10(6) cells/l was higher in those experiencing subsequent clinical failure (X2 test: 26.75; P < 0.00001). Multivariate analysis showed that baseline CD4 cell counts < 50 x 10(6) cells/l and AIDS at enrolment predicted failure; after adjusting for 3-month CD4 cell counts, this marker was the only one independently associated with clinical failure (hazard risk, 4.79; 95% confidence interval, 1.40-16.47). CONCLUSIONS: The 3-month immunological response is a reliable predictor of long-term clinical outcome.

AIDS-Related Opportunistic Infections↗

Clinical outcome and predictive factors of failure of highly active antiretroviral therapy in antiretroviral-experienced patients in advanced stages of HIV-1 infection.

OBJECTIVE: To verify the effectiveness of highly active antiretroviral therapy (HAART) and to identify any factors predictive of clinical outcome in a clinical setting. DESIGN: Observational study. METHODS: Treatment failure (i.e., the occurrence of new or recurrent AIDS-defining events, death or any definitive discontinuation) and the course of CD4+ cell counts and HIV RNA copies were evaluated in 250 heavily pretreated HIV-infected patients starting HAART [153 with indinavir (IDV), 55 with ritonavir (RTV), 43 with saquinavir (SQV)]. Univariate and multivariate analyses were performed to identify predictors of worse outcome. RESULTS: During a median follow-up of 8 months, 75 patients (30%) had treatment failure because of the occurrence of an AIDS-defining event or death (n = 24), inefficacy (n = 24), or severe intolerance (n = 27). Twenty new and six recurrent AIDS-defining events, and nine deaths occurred (six out of 20 AIDS-defining events and two out of nine deaths within 1 month of treatment). CD4+ counts were above 200 x 10(6)/l at AIDS diagnosis in only two patients. None of the SQV patients, 12 (7.8%) of the IDV patients, and 15 (27.3%) of the RTV-treated patients were considered non-compliant. The SQV-containing regimens independently correlated with treatment failure (relative risk, 2.46; 95% confidence interval, 1.20-5.03; versus IDV). Low compliance partially determined outcome in RTV-treated patients; both severe immunodepression and AIDS at baseline were predictive of treatment failure. There was a 10-fold increase in CD4+ cell counts in the patients treated with IDV and RTV; the best virological outcome occurred in IDV-treated patients, with 68.4% of patients showing undetectable HIV RNA copies after 6 months. CONCLUSIONS: HAART was effective in 70% of patients; low compliance and previous AIDS diagnosis represented predictive factors of therapy failure.

Adult↗

Predictors of cytomegalovirus disease, natural history and autopsy findings in a cohort of patients with AIDS.

OBJECTIVE: To identify the predictors of acquiring cytomegalovirus (CMV) disease, and to describe natural history, therapeutic management and autopsy findings in affected patients. DESIGN: Observational study of a consecutive cohort of AIDS patient diagnosed and followed in the same institution. METHODS: All of the patients with CMV were included. Statistical analyses were performed to establish the risk of acquiring the disease at or after AIDS presentation, survival, and the occurrence and time of relapses in relation to maintenance therapy. The presence of CMV infection at autopsy was also investigated. RESULTS: CMV disease was diagnosed in 304 (24.8%) out of 1,227 patients, its incidence increasing according to the year of AIDS diagnosis. Women, homosexual men, patients given zidovudine and Pneumocystis carinii pneumonia (PCP) prophylaxis before AIDS, and severely immunodepressed patients were at higher risk for the disease. CMV disease was an independent factor of worse survival (hazard ratio, 1.7 versus PCP; 95% confidence intervals, 1.28-2.13). Patients untreated during the acute phase had a 4.3 higher risk of dying than those treated. Relapses occurred less frequently and later in patients given continuous maintenance treatment (23 out of 113; 17 months) than in untreated patients (13 out of 16; 3 months) or those given discontinuous therapy (22 out of 40; 7 months), whereas survival was independent from treatment. CMV infection was found in 97 out of 134 patients at autopsy, but was unassociated with relapse. CONCLUSIONS: CMV is a severe disease whose frequency is higher in severely immunodepressed patients. Continuous treatment leads to a lower relapse rate even if it does not change survival or eradicate the infection.

AIDS-Related Opportunistic Infections↗

[Not Available].

UNLABELLED: Toxoplasmic encephalitis (TC) is the most common opportunistic infection of the Central Nervous System (CNS) in patients with the acquired immunodeficiency syndrome (AIDS). In order to investigate its clinical course, we reviewed the records of 133 patients with AIDS and central nervous system (CNS) toxoplasmosis treated at the Clinic of Infectious Diseases, University of Milan, between 1987 and 1992. The most common presenting symptoms were headache, confusion, disorientation and fever. Focal neurologic deficits were present in more than half of cases. Median CD4+ cell count at presentation was 65 per cubic millimeter. 25 (19%) out of 133 patients diagnosed with TC had undetectable anti-T. gondii IgG antibodies using an Elisa technique. Enhancing lesions on Computered Tomography (CT) were demonstrated in 119 (90%) patients. Solitary lesions were present in 26 cases; edema was evident in 19 patients. A complete clinica! and neuroradiological improvement after the acute episode was obtained in 126 (95%) of the cases. Adverse drug reactions occurred in 40 (30%) cases. Relapses occurred in 18/92 patients after a median time of 6 months. IN CONCLUSION: TC occurs in advanced stages of human immunodeficiency syndrome, and the absence of anti-T.gondii antibodies does not exclude the diagnosis. The clinical and radiographic response to therapy is usually rapid, but long-term treatment is frequently limited by adverse drug effects.

English Abstract↗