Abstract: Progressive multifocal leukoencephalopathy (PML) is a fatal neurological disease affecting the central nervous system. JC polyomavirus is the agent related to this disease. PML usually occurs in patients with HIV infection or other immunodeficiencies. We report a case of PML in a patient with idiopathic CD4+ cells deficit. The symptoms began with right arm hyposthenia followed by right hemiplegia. Blood analyses were normal, the only abnormal value was a marked decrease in CD4+ cells count with normal CD8+ cells. The magnetic resonance imaging (MRI) of the brain, showed multiple non-homogeneous lesions without enhancement in the left callous circumvolution and in the sub-cortical left frontal white matter. In the following two weeks, the patient had relevant progression in neurological deficits and a subsequent MRI demonstrated significant worsening. Because of the rapid clinical progression, we decided to start therapy with Cidofovir. The patient, after one month of admission, was slowly worsening in neurological functions. Clin Ter 2008; 159(5):325-327.
Abstract: OBJECTIVE: To evaluate the prevalence and incidence of nephrotoxicity in HIV-infected patients enrolled in the SCOLTA Project tenofovir cohort and to identify possible risk factors. DESIGN: The SCOLTA Project is a prospective, observational, multicenter study involving 25 infectious disease departments in Italy created to assess the incidence of severe adverse events in patients receiving new antiretroviral drugs. PATIENTS: The SCOLTA Project tenofovir cohort includes a total of 754 HIV infected patients. RESULTS: Data including grade II-IV creatinine elevations according to ACTG scale were available in 354 patients, 237 (67%) males with a mean age of 40.1+/-7.6 years enrolled in the SCOLTA Project tenofovir cohort. During a mean follow up of 19.5+/-11.5 months creatinine elevations were reported in 9/354 (2.5%) patients, all males. Mean duration of tenofovir therapy at the event was 9.5+/-5 months. The overall incidence was 1.6 (95% CI 1.5-1.7) per 100 person-years (p-y) and 0.5 (95% CI 0.4-0.6) p-y for grade III. No grade IV creatinine elevations were reported. Patients with nephrotoxicity were older and more frequently male, HCV infected, in CDC stage C and their CD4 cell count was significantly lower than those without nephrotoxicity. No significant difference was found between tenofovir co-administered antiretroviral drugs. CONCLUSIONS: Both prevalence and incidence of nephrotoxicity were low in patients receiving tenofovir in a non-selected clinical setting. Renal injury in patients receiving tenofovir seems associated with the presence of co-morbidities and with advanced HIV infection.
Abstract: BACKGROUND: It is not known whether antiretroviral therapy (ART) including lopinavir/r has a different effect on the lipid metabolism in HIV patients co-infected with HCV. This study investigated changes in lipid levels, comparing patients with HIV infection alone and those with HCV too, in the lopinavir/r cohort of the SCOLTA project. METHODS: We analyzed the data for the lopinavir/r nationwide cohort from 25 Italian infectious disease departments, which comprises 743 HIV-infected patients followed prospectively, comparing subjects with HIV-HCV co-infection and those with single-infection. RESULTS: At enrolment, co-infected patients had significantly lower mean cholesterol than HCV negative cases (162+/-43mg/dL vs. 185+/-52mg/dL, p=0.0009). Total and non-HDL cholesterol and triglycerides rose significantly from baseline in HIV single-infection patients, but not in those with co-infection. The patients with dual HIV-HCV infection, treated with an ART regimen including lopinavir/r, have only limited increases in total and non-HDL cholesterol and triglycerides. CONCLUSIONS: Changes in serum lipids in co-infected patients differed significantly from those in patients without HCV. It remains to be seen whether this is associated with a lower risk of progression of atherosclerotic disease.
Abstract: OBJECTIVE: To identify and characterize HIV-infected patients at higher cardiovascular risk in ordinary clinical settings. DESIGN: Multicenter, nationwide cross-sectional study. METHODS: Consecutive HIV-patients, attending scheduled visits at facilities involved in the Italian coordination group for the study of allergies and HIV infection (CISAI), were included between February and April, 2005. Their 10-year probability of acute coronary events was calculated using the Framingham Risk Score (FRS) as well as 3 other cardiovascular algorithms ("PROCAM", "PROGETTO CUORE", "SCORE"); Metabolic Syndrome (MS) was diagnosed according to the National Cholesterol Education Program definitions. An estimated 10-year CVD >or=10% and/or MS led to the diagnosis of high CV risk. We compared selected clinical features between high- and low-risk patients. RESULTS: A total of 1230 HIV infected patients (72% males, mean age of 43+/-9 years), 185 of whom treatment-naive, were evaluated. FRS gave the highest estimate of CV risk. The mean 10-year risk for acute coronary events according to FRS was 7.4+/-7.0. MS was present in 22% of the observed patients. Accordingly, 443 patients (36%) were classified at high risk. Twelve percent of the patients (n=142) had both a FRS >or=10% and a diagnosis of MS. The main single predictor of increased cardiovascular risk was smoking (60% of whole sample). A higher prevalence of clinically evident lipodystrophy and a higher CD4 T-cell counts were found both in patients with higher FRS and in patients with high FRS and MS (both p<0.001). CONCLUSIONS: The worst estimation of CV risk was obtained with the FRS algorithm. Clinical evidence of lipodystrophy and higher CD4 T-cell counts were closely associated to a worse cardiovascular risk profile.
Abstract: OBJECTIVE: To compare the prevalence of metabolic syndrome (MS) in HIV-positive patients with that from a sample of a general Italian population. DESIGN: Cross-sectional study. METHODS: A total of 1263 HIV-infected patients 18 years of age or older were recruited in 18 centers for infectious diseases in northern and central Italy. Controls were 2051 subjects aged 25 to 74 years representative of the residents of Monza, a town in Milan province, who were enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni study. RESULTS: The prevalence of MS in the HIV group was 20.8%, whereas in the control group, it was only 15.8%, with the difference being statistically significant. The age- and gender-adjusted risk of having MS in HIV-infected patients was twice as great as that in controls. Compared with controls, HIV-infected patients had a greater prevalence of the impaired fasting glucose, increased plasma triglycerides, and reduced high-density lipoprotein cholesterol components. MS prevalence was similar in treated and never-treated HIV-infected patients, and so were the various MS components. CONCLUSIONS: The risk of MS is greater in HIV-infected patients compared with the general population because of a greater prevalence of lipid and glucose abnormalities. The prevalence of MS and its components is similar in treated and untreated HIV-positive patients.
Abstract: The present document contains recommendations for assessment, prevention and treatment of cardiovascular risk for HIV-infected patients. All recommendations were graded according to the strength and quality of the evidence and were voted on by 73 members of the Italian Cardiovascular Risk Guidelines Working Group which includes both experts in HIV/AIDS care and in cardiovascular and metabolic medicine. Since antiretroviral drug exposure represents only one risk factor, continued emphasis on an integrated management is given. This should include prevention and treatment of known cardiovascular risk factors (such as dyslipidaemia, diabetes, insulin resistance, healthy diet, physical activity, avoidance of smoking), but also rational switch of antiretroviral drugs. A rational switch strategy should consider both metabolic and anthropometric disturbances and effectiveness of antiretroviral regimens.
Abstract: HIV-infected patients may undergo renal damage related to the HIV infection itself, to the presence of co-infections, arterial hypertension, diabetes or to the exposure to nephrotoxic drugs. Tenofovir has been associated with the development of acute renal failure with Fanconi syndrome and acute tubular necrosis and, albeit rarely, with chronic liver disease. Patients with low CD4 cell count, low body weight and with concomitant diseases such as arterial hypertension and diabetes or co-infections with HCV, HBV or Treponema pallidum seem at higher risk of tenofovir-related nephrotoxicity. Other risk factors include previous exposure to nephrotoxic drugs and the association of tenofovir with boosted protease inhibitors or with didanosine. However, from the analysis of published papers the incidence of tenofovir-related renal toxicity seems low, as confirmed also by our personal casuistry (SCOLTA Project). Thus, a careful selection of patients including the evaluation of existent renal disease before starting an antiretroviral regimen including tenofovir is necessary to prevent renal damage. Furthermore, frequent monitoring of renal function in patients at higher risk of renal damage is strongly recommended, as well as a tenofovir dose adjustment if an alteration of renal function is detected.
Abstract: Hepatitis C virus common transmission routes and HCV coinfection is frequent in persons living with HIV. Liver enzyme elevation following the initiation of antiretroviral therapy is frequently seen in HIV-infected patients with chronic liver disease, particularly those with chronic hepatitis C. This complication may lead to treatment discontinuation, complicating HIV therapeutic management. Multiple factors influence the risk of liver toxicity under antiretroviral therapy, including the specific drug in use (e.g. use of full doses of ritonavir), and environmental factors (e.g. alcohol abuse). However a beneficial effect of antiretroviral therapy on liver disease has been supported by some studies. Despite increasing knowledge of HCV/HIV coinfection, there is no clear consensus on how to treat HIV in HCV-coinfected patients An Italian group of experts were invited to discuss in detail the current risks and implications of antiretroviral treatment in HIV-infected persons with chronic hepatitis C, and their main conclusions are summarized in this consensus document.
Abstract: The SCOLTA project (Surveillance Cohort Long-term Toxicity Antiretrovirals) is a system for online surveying of adverse reactions to recently commercialized antiretroviral drugs and a "sentinel" for unexpected and late adverse reactions arising during any antiretroviral treatment (available at: http://www.cisai.info). To date, 25 Italian departments of infectious diseases have participated at the project. The New Drugs Project is a prospective, multicenter, observational pharmacovigilance study involving 1 cohort of patients for each new drug. All patients who were consecutively started on lopinavir (LPV), tenofovir (TDF), peginterferon (IFN), atazanavir (ATZ), enfuvirtide (T-20), and tipranavir (TPV) were enrolled. All grade III or IV adverse events (according to the AIDS Clinical Trials Group definitions) are reported on the web site. The Unexpected Events Project identifies unexpected adverse reactions during treatment and reports them. This paper presents the preliminary findings for the New Drugs Project. Between October 1, 2002, and March 30, 2004, 1184 patients were enrolled. The lopinavir/ritonavir (LPV/r) cohort comprises 703 patients, the TDF cohort 585, IFN 35, ATZ 95, T-20 10, and TPV 8. So far 100 grades III and IV adverse events have been reported, 73 in the LPV/r group. In this cohort the rate of adverse events per 100 person-years was 14.2 on the basis of all patients treated, 9.8 for treatment-naive patients, and 15 for treatment-experienced patients. These findings, though preliminary, show that this data collection method gives timely real-life information from which to assess the impact of short- and long-term toxicity of new antiretroviral drugs.
Abstract: We describe the hepatotoxicity encountered in a cohort of HIV-positive patients treated with lopinavir/ritonavir. We used the database from the SCOLTA project, an on-line pharmacovigilance programme involving 25 Italian infectious disease centres. A total of 755 patients were followed, over a mean observation period of 16 months. The incidence of severe events was low despite the high prevalence of patients co-infected with hepatitis virus at enrollment.
Abstract: In the last few years there are increasing evidences suggesting that osteopenia and osteoporosis are frequent among HIV positive patients. It is still not clear if the bone demineralization is a direct consequence of viral infection or of the antiretroviral drugs. Studies to date therefore give conflicting results. We performed a study to evaluate the prevalence of osteopenia and osteoporosis in HIV positive patients, either untreated or receiving antiretroviral therapy, to asses the frequency of these conditions and the role of antiretroviral drugs.
Abstract: PURPOSE: This study set out to describe the frequency of lipodystrophy, and identify its risk factors, in HIV-positive patients treated with HAART containing at least one protease inhibitor (PI). We analyzed the data collected in the CISAI study. METHODS: The CISAI is a multicenter cohort study that has enrolled 1480 patients. We assessed whether patients had lipodystrophy at a medical visit, with follow-up visits by the same physician at least every 2 months, and also on the basis of patients' own reports. RESULTS: The lipodystrophy syndrome was detected in about 25% of the patients. Multivariate analysis showed the risk of lipodystrophy was correlated with female sex (RR 1.5; 95% confidence interval, CI, 1.2-2.1), with older age, with homosexuality (RR 1.5; 95% CI 1.0-2.4), with overt disease (RR 1.4; 95% CI 1.1-1.8) and with the duration of treatment before entering this study. The RR for ritonavir was higher than for the other PI (RR 1.4; 95% CI 0.9-1.9). Among patients receiving concomitant antiretroviral therapy the risk of lipodystrophy was greater with stavudine (RR 1.7; 95% CI 1.3-2.3). CONCLUSIONS: The study confirmed the high frequency of the lipodystrophy syndrome among patients treated with PI.
Abstract: Risk factors in the development of adverse reactions in HIV-1-infected patients treated with highly active antiretroviral therapy (HAART) containing protease inhibitors are poorly understood. To identify predictors of protease inhibitor-associated adverse events, we are conducting a prospective, cohort, multicenter study on HIV-positive patients starting treatment with at least one protease inhibitor. Rate ratios (RR) of adverse events were calculated, and logistic regression was used to adjust simultaneously for the potentially confounding effects of selected variables, according to the Cox model. A total of 1477 patients have been enrolled up to April 2000, having an average age of 37.1 years (SD +/- 8.1); 1066 (72.2%) were male. Where risk factors for HIV infection are concerned, the distribution was as follows: 48.1% intravenous drug users, 31.6% heterosexual contacts, 16.2% homosexual males and 0.7% blood transfusion. Average CD4+ lymphocyte count at enrollment was 265 cells/mmc (SD +/- 201). Average follow-up time is equal to 17.8 months (range 1-32). The risk of developing adverse reactions is significantly increased in female patients, older patients, hemophiliac subjects and in subjects with hepatitis. Patients treated with ritonavir, the association ritonavir-saquinavir HGC, stavudine and efavirenz have significantly increased incidence of adverse reactions in PI-containing regimens; conversely, saquinavir HGC, zidovudine and lamivudine use was associated with a lower risk of developing adverse reactions.
Abstract: The introduction of protease inhibitors has proven a watershed in human immunodeficiency virus infection therapy and has initiated an era of highly active antiretroviral therapy. However, the numerous data on the effectiveness of these therapeutic regimens have been cited with an ever-growing number of communications concerning adverse reactions. In particular, the widescale use of protease inhibitors has underlined a series of events not evidenced in the controlled clinical studies that permitted the registration of these drugs. We are conducting a cohort multicenter study to evaluate the incidence of adverse events during treatment with protease inhibitors. To date, 4 cases of bilateral osteonecrosis of the femoral head have been reported out of 1073 person-years. While the pathogenesis of this event is unclear, it may be a long-term complication of protease inhibitor treatment.
Abstract: OBJECTIVE: To assess the probability that protease inhibitor (PI) therapy might be discontinued because of adverse events (AE) and to evaluate the incidence rate of adverse reactions during PI treatment. DESIGN: A prospective cohort, multicenter study on HIV-positive patients starting treatment with at least one PI. SETTING: Ten departments of infectious diseases in Northern Italy. PATIENTS: A total of 1207 patients who started PI therapy in September 1997 and were consecutively observed up to April 1999. MAIN OUTCOME MEASURES: Adverse reactions following initiation of PI therapy, and time to therapy discontinuation due to AE. RESULTS: During the study period, 35.9% patients presented adverse reactions of any grade, whereas 9.7% presented at least one serious AE. After 12 months of treatment, the percentage of patients who had interrupted treatment was 36% of ritonavir-treated patients, 14.2% of those treated with indinavir, 13.6% of ritonavir-saquinavir hard gel capsules (HGC)-treated patients, and 8.5% and 2.1%, respectively, for those treated with nelfinavir and saquinavir HGC. Women and patients with hepatitis experienced a significantly greater number of adverse events compared with other categories. Gastrointestinal events were more frequently observed in patients treated with either ritonavir alone or in combination with saquinavir HGC, as well as in patients receiving nelfinavir, although in this group serious events were rare. Here again, neurologic, metabolic, and hepatic toxicity occurred more frequently in ritonavir and ritonavir-saquinavir HGC treated patients. Allergic reactions were more often observed in patients receiving nelfinavir. Indinavir-treated patients presented the highest incidence of renal toxicity. CONCLUSION: Ritonavir is the drug associated with the largest number of reactions, which appear during the first few months of treatment. Saquinavir HGC and nelfinavir are the best tolerated drugs in a clinical setting.
Abstract: Our study was undertaken to evaluate if desensitization treatment is more effective than rechallenge in preventing hypersensitivity reactions in HIV-positive patients with previous allergic reactions to TMP-SMX; the secondary aim was to evaluate the frequency of reactions to TMP alone. This was a randomized, multicentre open study. Patients with previous documented hypersensitivity to TMP-SMX who required primary or secondary PCP prophylaxis were enrolled; subjects who had previously had serious adverse reactions to TMP-SMX were excluded. All eligible patients assumed 200 mg TMP for 14 days and in case of no reactions were randomized for desensitization or rechallenge with TMP-SMX. The patients were then followed up by periodical visits for six months. Seventy-three patients were enrolled; 14 subjects (19%) presented reactions on TMP alone during the pre-enrollment phase. The remaining 59 subjects were randomly assigned to the two treatment groups: 34 carried out desensitization (group 1) and 25 rechallenge (group 2) with TMP-SMX. Seven patients in group 1 (20.5%) and seven in group 2 (28%) showed hypersensitivity reactions during treatment; this difference was not statistically significant. No serious reaction occurred in either group. This study showed the comparable effectiveness of the desensitization procedure and rechallenge in patients with a previous, not serious, allergic reaction to TMP-SMX.
Abstract: The aim of our study is to compare the tolerability of zidovudine/lamivudine/indinavir when used in post-exposure prophylaxis (PEP) subjects and in HIV-infected patients. HIV-negative patients were enrolled as part of the surveillance protocol for professional exposure at the Luigi Sacco Hospital in Milan. HIV-positive patients were selected among all subjects undergoing treatment with zidovudine/lamivudine/indinavir from the CISAI cohort, an Italian cohort for the evaluation of adverse reactions to HAART. In both studies patients were followed prospectively and the severity of the reactions was evaluated using the AIDS Clinical Trial Group adverse experience grading scales. Up to September 1999, 37 HIV-seronegative subjects had undergone treatment with zidovudine/ lamivudine/indinavir. From a total of 1207 patients belonging to the CISAI cohort, 199 were identified as being treated with the same regimen. The frequency of adverse events in the PEP subjects was 70.3% compared to 11.1% for HIV-infected patients. In the first group, adverse events caused treatment interruption in 21 subjects (56.7%) versus 14 patients (7%) among the HIV-infected group. Only one case of a severe event (grade 3-4) was observed in the prophylaxis group against 12 in the treatment group. Our study shows that treatment interruption is eight times higher in HIV-negative subjects compared to HIV-seropositive patients, and that the incidence of adverse events is approximately six times higher, though such events, are for the most part, not severe.
Abstract: PURPOSE: To establish the exact cause and effect relationship between protease inhibitors (PIs) and adverse events. MATERIALS AND METHOD: Prospective, cohort, multicenter study on HIV-positive patients who are beginning treatment with a PI. Causal relationships are evaluated using the RUCAM algorithm. RESULTS: Since the beginning of the study 1207 patients have been enrolled. Average time of observation is 10.7 months. To date, 784 adverse events have been observed, distributed as follows: excluded 3.8%, improbable 18.5%, possible 41.3%, probable 30.1%, and highly probable 6.3%. Saquinavir shows a statistically significant difference in the rate of non-correlated events with respect to other groups. CONCLUSIONS: Over 20% of adverse events during PI treatment are shown to be non-correlated to these drugs. Saquinavir shows the highest rate of non-correlated events.
Abstract: 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.
Abstract: This trial was conducted to study the frequency of the slow acetylator phenotype in asymptomatic HIV patients having no previous reaction to sulfa-drugs, and to compare this frequency with the frequency found in healthy controls. Results show that HIV alone is not capable of modifying the acetylator phenotype; the prevalence of slow acetylator phenotype is the same in immune competent subjects and HIV-positive patients. It is more common in HIV-positive patients with a CD4+ lymphocyte count of less than 200 mm-3.
Abstract: In this study, 9 patients with primary hypercholesterolemia were treated with pravastatin. They received a daily dose of 20 mg for 12 weeks. Results showed a significant reduction in total and LDL cholesterol, whereas no significant difference was observed in HDL and triglyceride levels after treatment. No adverse effects were observed.
