Efficacy and safety of boosted and unboosted atazanavir-containing antiretroviral regimens in real life: results from a multicentre cohort study.

BACKGROUND: Atazanavir (ATV) has demonstrated high efficacy and safety in both treatment-naïve and treatment-experienced patients. Some comparative data are available on the durability of ritonavir-boosted (ATV/r) and unboosted formulations, but there are no data on clinicians' motivations for choosing one or another in everyday practice. The aim of this study was to evaluate the long-term efficacy of boosted and unboosted ATV in a cohort of treatment-experienced patients. METHODS: All patients included in the study were enrolled in an observational cohort within the Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) Project. Data on CD4 cell count, HIV viral load, metabolic parameters and adverse events of grade 3-4 are collected through an on-line system every six months. The duration of treatment with ATV was evaluated using the Kaplan-Meier curve and boosted and unboosted regimens were compared using the log-rank test. RESULTS: A total of 509 patients starting ATV as a component of their antiretroviral therapy were enrolled in the SCOLTA Project at the time of the study. Boosted ATV was received by 379 patients (74.5%) while 130 (25.5%) were treated with the unboosted formulation. The last therapeutic regimen did not influence the choice of ATV formulation. The mean observational time was 23.9 months. At the end of follow-up, 58.5% of patients on unboosted ATV and 58.1% of patients on ATV/r continued the treatment and no statistically significant differences were observed for ATV durability between the formulations or among the single causes of therapy interruption. CONCLUSIONS: Our results suggest that, in unselected clinical settings, ATV-containing antiretroviral therapy is durable and safe in both its formulations.

[A case of community-acquired MRSA (CA-MRSA) sepsis complicated by meningoencephalitis and cerebral abscess, successfully treated with linezolid]. / Un caso di sespi da MRSA comunitario (CA-MRSA) complicata da meningoencefalite ed ascesso cerebrale trattato con successo con linezolid.

The authors describe a clinical case regarding a young female patient affected by sepsis due to methicillin-resistant Staphylococcus aureus (MRSA), associated to meningoencephalitis and cerebral abscess. The patient had no contact with hospitals in the months prior to illness and had always been healthy. She recovered thanks to linezolid therapy. The MRSA strain proved positive for Panton-Valentine leukocidin (PVL positive) and was therefore defined as community-acquired MRSA (CA-MRSA).

[Prevention of nosocomial infections: surveillance based on microbiological data]. / Effetti del monitoraggio sistematico sulla prevenzione delle infezioni ospedaliere: la sorveglianza basata sui dati del laboratorio di microbiologia.

BACKGROUND: In the C. Poma Hospital of Mantua we have been using a system of continuous surveillance of nosocomial infections based on microbiological data for the past 4 years. This monitoring estimates the incidence of the microorganisms found in cultures, especially those at risk of causing nosocomial infections. MATERIALS AND METHODS: Since June 2001 microbiological data have been registered using the Mercurio-Dianoema software and elaborated by means of Microsoft Excel in order to obtain information about isolated bacteria, especially those resistant to antibiotics. RESULTS: Surveillance in "critical" wards revealed the presence of Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans in the intensive care unit in the period 2003-2005. The most frequent bacteria in hemodialysis have been coagulase-negative Staphylococci and Staphylococcus aureus, with variable methicillin resistance. CONCLUSION: The analysis of microbiological data has promoted effective measures to reduce the incidence of these bacteria (increased rules of good practice, hand washing, etc.). If nosocomial infections or high-risk microorganisms occur, assessments are carried out; monitoring of the antibiotic resistance of the bacteria is very important.

[Epidemiologic surveillance of multi-drug resistant Pseudomonas aeruginosa in Mantova Hospital (Italy)]. / Sorveglianza epidemiologica di Pseudomonas aeruginosa multiresistente nell'Ospedale di Mantova.

For the period 2002-2005 we verified and compared the data of the prevalence and resistance of Pseudomonas aeruginosa (PA) isolated in Mantova Hospital (Italy) with the data from the international database. From the first six-month period of 2004 a significant increase was found (9% vs 28.8%) in the prevalence of multi-drug resistant PA (MDR-PA). The principal wards involved were the Intensive Care Unit and the Department of Respiratory Diseases. A significant increase in resistance rates was observed for all antimicrobials tested, in particular for aztreonam, ceftazidime, ciprofloxacin, gentamycin and imipenem. The lowest dual resistance rates were observed between amikacina with piperacillin/tazobactam, while the highest were for those that included ciprofloxacin and beta-lactams (aztreonam, cefepime). In this study we confirm the importance of continuous surveillance of laboratory data and tightening local control measures for nosocomial infections in order to prevent the spread and selection of MDR-PA.

Holmes' tremor following midbrain Toxoplasma abscess: clinical features and treatment of a case.

The label Holmes' tremor defines a rare symptomatic movement disorder frequently occurring with midbrain damage. It appears at rest and worsens adopting a posture and on attempting movements. We describe the case of a patient with Holmes' tremor due to a presumed Toxoplasma abscess of the midbrain. The positive response to a combined therapy with levodopa and isoniazid is also reported.

Short-term adverse effects from and discontinuation of antiretroviral post-exposure prophylaxis.

OBJECTIVE: To evaluate short-term toxicity from and discontinuation of antiretroviral combination prophylaxis in HIV-exposed individuals in Italy. DESIGN: Longitudinal, open study conducted by prospective collection of data in the National Registry of PEP. SETTING: All the Italian centres dedicated to HIV related care and licensed by the Ministry of Health to dispense antiretroviral drugs. STUDY POPULATION: Health care workers and other persons consenting to be treated with post exposure prophylaxis (PEP) after exposures to HIV. RESULTS: Until October, 2000, 207 individuals receiving two nucleoside reverse transcriptase inhibitors (NRTIs), and 354 receiving two NRTIs plus a protease inhibitor (PI) were enrolled. More individuals experienced side-effects in the 3-drug group (53% and 62%, respectively; OR 0.68, (95% CI 0.48-0.98), p < 0.03). However, the proportion of individuals discontinuing prophylaxis because of side-effects did not differ significantly between the 2 groups (21% and 25% respectively; OR 0.82 (95% CI 0.53-1.26); p=0.4). The 43 individuals in the 2 NRTI group discontinued PEP after a mean of 10.4 days of treatment (median 8, range 1-27), similarly to the 88 discontinuations observed in the 3-drug group (mean duration 10.5 days, median 7.5, range 1-26). Type and incidence of specific adverse effects were similar to those reported in the literature. CONCLUSION: Our study indicates that the difference in the proportion of individuals developing side effects and discontinuing PEP is not significant. The rate of discontinuation because of protease inhibitor side-effects does not justify per se the initial use of a less potent PEP regimen. We suggest initiating PEP with a three-drug regimen and discontinuing the protease inhibitor in the case of adverse effects.

Computed tomography and magnetic resonance imaging of pathologic conditions of the middle ear.

Computed tomography (CT) is an excellent technique for demonstrating even small abnormalities of the thin and complex bony structures of the middle ear. For this reason, it is the modality of choice in the study of conductive hearing loss (CHL). However, not every patient complaining of CHL requires a CT study. In fact, established indications encompass complex conditions, such as the complications of acute and chronic otomastoiditis, the postoperative ear in chronic otomastoiditis or in the localization of prosthetic devices, and the assessment of congenital or vascular anomalies. Particularly, the precise extent of bone erosion associated with cholesteatoma is correctly demonstrated by high resolution CT. Conversely, although fistulization through the tegmen tympani or the posterior wall of temporal bone is usually detectable by CT, the actual involvement of meninges and veins are better assessed by magnetic resonance (MR). MR is also indicated when complicated inflammatory lesions are suspected to extend into the inner ear or towards the sigmoid sinus or jugular vein. Neoplasms arising from or extending into the middle ear require the use of both techniques as their combined data provide essential information. Most important data for surgical planning concern the destruction of thin bony structures and the relationships of the lesion with the dura and surrounding vessels. DSA and interventional vascular techniques maintain an essential role in the presurgical work-up and embolization of paragangliomas extended into the middle ear.

Naive CD4+ T lymphocytes express high levels of Bcl-2 after highly active antiretroviral therapy for HIV infection.

The mechanism causing the increasing number of peripheral T cells after highly active antiretroviral therapy (HAART) is still unclear. The bcl-2 oncogene prevents spontaneous apoptosis (SA) in lymphocytes. Spontaneous apoptosis could be a determinant of HIV immunodeficiency and can be reversed by HAART including protease inhibitors (PI-HAART). The aims of our study were to measure Bcl-2 protein expression in memory (CD45RO+) and naive (CD45RO-) CD4+ and CD8+ T lymphocytes of HIV+ patients and to correlate it with efficacy of PI-HAART. Forty-nine HIV+ patients (cases) and 26 HIV- individuals (controls) were evaluated. Patients receiving PI-HAART, and who had undetectable HIV plasma viral load (VL-, n = 21), had higher levels of Bcl-2 than did VL+ patients (n = 28), both in CD4+ cells (p < 0.0001) and in CD8+ cells (p < 0.001). VL+ patients had lower Bcl-2 levels than did controls in CD8+ cells (p = 0.02), but not in CD4+ cells (p > 0.05). Interestingly, VL- patients had higher Bcl-2 expression than did controls both in CD4+ cells (p < 0.0001) and in CD8+ cells (p = 0.03). In a subcohort of the same patients, Bcl-2 was significantly higher in VL- patients (n = 10) than in controls (n = 12), both in naive CD4+ cells (p < 0.0001) and in naive CD8+ cells (p = 0.01). Naive CD4+ cells had higher Bcl-2 expression in VL- than in VL+ patients (p = 0.01). In a subsequent longitudinal study of nine HIV patients, naive CD4+ cells increased after effective PI-HAART (p = 0.03), which paralleled an increase in Bcl-2 expression in the same cells (p = 0.02). In conclusion, upregulation of bcl-2 could be a mechanism of immune reconstitution of naive CD4+ T cells induced by PI-HAART.

Liver damage and kinetics of hepatitis C virus and human immunodeficiency virus replication during the early phases of combination antiretroviral treatment.

In order to assess the relationship between human immunodeficiency virus (HIV) RNA, hepatitis C virus (HCV) RNA, CD4, CD8, and liver enzymes during combination antiretroviral therapy, these parameters were measured in 12 HIV-HCV-coinfected patients (who were naive for antiretrovirals) on the day before and 3, 7, 14, 28, 56, and 84 days after initiating the following treatments: stavudine and lamivudine in all patients, indinavir in 6 patients, and nevirapine in 6 patients. HIV RNA declined rapidly, CD4 cells increased slowly, and CD8 cells and liver enzymes were stable. HCV RNA showed a transient significant increase at days 14 and 21 (7.33+/-0.16 [mean +/- SE] and 7.29+/-0.2 log copies/mL vs. 7+/-0.2 log copies/mL at baseline; P<.05). These changes were similar in both treatment groups. A 2-fold alanine aminotransferase increase was observed in 4 of 12 patients; 4 of 4 patients showed increased HCV RNA. The relationship between HCV RNA increase and HIV RNA decrease indicates virus-virus interference. An HCV RNA increase may cause significant liver damage only in a minority of patients.

Prognostic factors correlated with survival in AIDS patients.

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.

HIV-1 pharmacoresistance: clinical and therapeutic implications.

The primary objective of antiretroviral therapy is to suppress viral replication as soon as possible, as much as possible and for as long as possible, a concept so clearly emphasized by David Ho in 1995: "Treat HIV early and hard!". That, however, seems an ideal objective by a number of reasons, recently recognized as fundamental: unavailability of treatments able to eradicate the infection, difficulty to reach compliance to HAART (Highly Active Antiretroviral Therapy), emergence of drug resistance and cross-resistance. (Cross)-resistance in particular has the potential both to waste future therapeutic options and to be transmitted during HIV infection. Therefore, HIV pharmacoresistance has to be considered one of the most challenging focal point in research on antiretroviral therapy. Understanding of causes, evolutionary patterns and consequences of resistance in terms of viroimmunological and clinical response appears inescapable to strategically plan and monitor treatment. Rather than to eradicate the infection with regimens more and more hard but more and more difficult to comply with, the realistic approach is to construct a strategic therapeutic itinerary tailored to the bio-psycho-social patient conditions and to the saving of therapeutic options. The latter means the rational sequencing of the drug employment for a long-term therapy, potentially life-long.

Changing patterns of HIV transmission and better targeting for intervention strategies.

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.

Beta-blockade antagonism of tyramine-induced rise in blood pressure.

The effect beta-adrenoceptor blockade on the pressor response to tyramine has been investigated in 6 healthy volunteers, each submitted to an i.v. tyramine pressor test before and after 7 days of propranolol 40 mg b.d. or indenolol 60 mg o.d. Tyramine was given as i.v. boluses of 1-6 mg, alternating with saline, in a randomized, single blind fashion. Prior to treatment tyramine caused a temporary, dose-dependent increase in systolic and diastolic blood pressure, whilst the heart rate remained unaffected. Both propranolol and indenolol reduced the pressor response to tyramine, as shown by a significant increase in ED15, i.e. the dose of tyramine required to increase systolic blood pressure by 15%.