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G Carosi

Publications and source records attributed to G Carosi.

At least 19 recordsLinked to original sources
PubMed2006

Key questions in antiretroviral therapy: Italian Consensus Workshop (2005).

A panel of leading Italian specialists in infectious diseases, virologists and immunologists met in Rome in 2005 to review critical data and discuss recommendations for each of the key questions in antiretroviral therapy today: When to start treatment? How to start? When to switch? What to switch to? Whether to stop or not to stop treatment, and how? The method of a nominal group meeting was used and recommendations were graded for their strength and quality using a system based on the one adopted by the Infectious Diseases Society of America. Main conclusions are summarized and critically discussed in this consensus statement, as well as some of the most recent data supporting these recommendations are provided.

Anti-HIV Agents↗
PubMed2006

Impact of unreported HIV-1 reverse transcriptase mutations on phenotypic resistance to nucleoside and non-nucleoside inhibitors.

An extended spectrum of HIV-1 reverse-transcriptase (RT) mutations in HAART-treated patients has been recently described. To verify the possible association of previously unreported RT mutations with a decrease of phenotypic susceptibility to nucleoside (NRTIs) and non-nucleoside (NNRTIs) RT inhibitors, the RT sequence of 328 HIV-1-positive patients (102 naïve and 226 treated with HAART participating in either the PhenGen or Genpherex study) was analyzed. All treated patients were tested at the time of therapeutic failure with both phenotypic (Antivirogram, Virco) and genotypic analyses (VircoGen); the frequency of RT substitutions (positions 1-240) with respect to consensus B was compared to that of naïve patients using a Chi-square test. Amino acid changes at 13 positions not included in the IAS list of resistance-associated mutations were detected more frequently in treated than in naïve subjects. The mutations involving 10 of these positions were associated with a reduced susceptibility to antiretroviral drugs; K20R, T39A, K43EQN, E203KD, H208Y, and D218E were correlated with NRTI resistance while mutations K101EQP, H221Y, K223EQ, L228HR were associated to NNRTI resistance. A correlation was found between K20R and lamivudine resistance (P = 0.006) while T39A (P = 0.005), K43EQN (<0.001), E203KD (P = 0.010), and H208Y (P = < 0.001) seemed to be associated with a previous use of zidovudine and stavudine and with the development of thymidine analog resistance. For H208Y, an association with use/resistance to abacavir (P = 0.004) was also noted. D218E showed a weak association to didanosine resistance (P = 0.013). The data confirm that previously unreported mutations are associated with antiretroviral drug experience and, more importantly, with a reduced susceptibility to NRTIs and NNRTIs.

Adult↗
PubMed2005

HIV-1 genotype resistance pattern and evolution in patients failing nelfinavir-containing regimens.

Clinical and in vitro studies have suggested that nelfinavir (NFV)-containing regimens may not preclude the use of other protease inhibitors (PIs) in treatment sequencing. We have studied the prevalence of 30N mutation in a human immunodeficiency virus-1 (HIV-1)-infected cohort and the virological response to a PI-containing regimen in patients who had previously failed NFV. A total of 335 patients were included in the study; 32 of them were antiretroviral-naive and 303 were antiretroviral-experienced (251 were PI-experienced). Mutations 30N and/or 90M were not detected in sequences obtained either from the antiretroviral naive or non-PI-experienced patients. The 30N mutation was detected in 21/251 (8.3%) of PI-experienced patients and 90M in 103/251 (41%). Moreover, we have observed that the 88D and 77I mutations were present in more than 75% of patients harbouring the 30N HIV-1 variant and the 71T mutation was present in almost 50% of them. Finally, mutations 30N+90M were never detected together in the same HIV-1 strain. The 30N and 90M mutations were not observed together. The presence of mutations at positions 36, 46, 71, 77, and/or 88 in a 30N background, increases the risk of the cross-resistance to other PIs. The use of NFV as a first-line PI, as an application of drug sequencing strategies, may help preserve future PI options.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Risk factors for myocardial infarction in HIV-positive patients.

We describe the clinical characteristics of 12 HIV-infected patients who suffered from myocardial infarction (MI) in our clinical cohort. They were compared with a control group matched (1:2) for factors related to cardiovascular risk (age, gender, smoking habit, risk factor for HIV acquisition, hypertension, family history for relevant cardiovascular events, and body mass index) by conditional (fixed-effect) logistic regression analysis. Among patients with MI, 6/12 had never used protease inhibitors (PIs) or were antiretroviral therapy naive. The only variables marginally associated with MI were nadir CD4+ T-cell count <50/mm(3) (odds ratio (OR): 7.2; 95% confidence interval (CI) 0.81-64.2; P: 0.077) and zenith >100,000 HIV RNA copies/mL (OR: 7; 95% CI 0.81-60.2; P: 0.076) at univariate analysis. Moreover, the use of PIs did not result in being associated with the risk of MI. Our data show that in HIV-infected patients, PI use does not seem to have any negative impact on MI while the possible impact of advanced HIV infection itself needs further investigations.

Adult↗
PubMed2004

Lopinavir plasma levels in salvage regimes by a population of highly active antiretroviral therapy-treated HIV-1-positive patients.

Increased lopinavir (LPV) exposure obtained in vivo through combination with low-dose ritonavir may overcome a certain grade of resistance but not all. We sought to analyze LPV variability and possible risk factors. LPV trough plasma concentrations were determined by high-performance liquid chromatography after 1, 4, and 12 weeks from salvage regimens and tested in both univariate and multivariate regression analyses with age, gender, weight, risk factors for HIV acquisition, hepatitis C virus reactivity, hepatitis B surface antigen positivity, baseline aspartate transferase (AST) or alanine transferase (ALT) levels, creatinine, non-nucleoside reverse transcriptase inhibitors (NNRTIs) or tenofovir as concomitant drugs, and NNRTIs administered in the previous regimen. Fifty-six patients were included into the study. Among them, 8 of 56 (14.3%) at week 1, 12 of 56 (21.4%) at week 4, and 9 of 56 (16.1%) at week 12 had suboptimal LPV plasma concentrations, defined as trough concentration less than 4 microg/mL. No correlation was found between LPV trough concentrations and assessed variables. In conclusion, pharmacokinetic variability and low LPV concentrations have been found, supporting the use of therapeutic drug monitoring in those starting this drug.

Adult↗
PubMed2004

Prevalence of drug resistance and newly recognised treatment-related substitutions in the HIV-1 reverse transcriptase and protease genes from HIV-positive patients naïve for anti-retrovirals.

The aim of this study was to assess the prevalence of genetic changes in either the HIV reverse transcriptase (RT) or protease (Pro) genes in a cohort of patients naïve for anti-retroviral therapy. Of 61 patients, 43 (70.5%) were infected with HIV strains harbouring at least one resistance-related mutation, with 41 (67.2%) harbouring newly recognised treatment-related mutations. Among the 61 patients, the prevalence of specific mutations in the RT gene was as follows: 39A, 1.6%; 43E, 1.6%; and 228H, 1.6%. The prevalence of specific mutations in the Pro gene was as follows: 11I, 1.6%; 13V, 26.2%; 35D, 19.6%; 45R, 1.6%; 58E, 1.6%; 62V, 31%; 72V, 11.4%; 72M, 6.5%; 72T, 3.2%; 75I, 1.6%; and 89M, 13%. A higher prevalence of newly recognised mutations was found in strains from patients infected through sexual practices (30/36 = 83.4% vs. 11/25 = 44%; p 0.0023; OR 10.91; 95% CI 3.14-40.39). These findings support the use of resistance testing in patients naïve for anti-retroviral therapy, and suggest that the possible impact of newly recognised treatment-related mutations on clinical outcome requires further investigation.

Adult↗
PubMed2004

"Solving the puzzle" of current HAART: what key strategic trials are needed?

A growing number of antiretroviral drugs have brought substantial advancements into treatment for HIV-1 infection, reducing AIDS-related mortality and morbidity in HIV infected patients. However, antiretroviral regimens are complex, cause several side effects, pose difficulties to patients' adherence to treatment and can determine emergence of viral drug resistances, the main draw back of non-adherence to drug regimens and/or sub-optimal drug bioavailability. As a consequence, new more effective and tolerable antiretroviral agents and regimens are needed, as well as new strategies for HIVdisease management. Strategically driven clinical researches are needed to address these issues.

Anti-HIV Agents↗
PubMed2003

Clinical stability in human immunodeficiency virus-infected patients with community-acquired pneumonia.

Clinical stability (CS), defined as normalization of vital signs, is often used to manage inpatients with community-acquired pneumonia (CAP). The main objective of our study was to identify a reliable definition of CS for human immunodeficiency virus (HIV)-positive patients with CAP. During an 18-month period, 437 HIV-positive Italian inpatients with CAP were enrolled in the study. We used 3 definitions of CS (from a less conservative [definition 1] to a more conservative [definition 3] definition) based on combinations of different thresholds for vital signs. Assessments were performed at admission and daily during the hospital stay. For the 3 definitions, 14.9%, 8.0%, and 4.8% of patients were stable at baseline, with deterioration after reaching CS in 7.16%, 4.76%, and 2.05%, respectively. The 8 patients whose conditions deteriorated after reaching CS definition 3 (systolic blood pressure, >90 mm Hg; pulse, <90 beats/min; respiratory rate, <20 breaths/min; oxygen saturation, >90%; temperature, <37 degrees C; ability to eat; and normal mental status) survived and were discharged from the hospital. The more conservative definition of CS appears to be reliable for the management of HIV-infected patients with CAP.

Adult↗
PubMed2003

HIV/HTLV co-infection: frequency and epidemiological characteristics among patients admitted to an Italian hospital.

BACKGROUND: Human T-cell leukemia/lymphoma viruses (HTLV) and HIV share identical modes of transmission and co-infections may be detected in populations that are highly exposed to common risk factors. MATERIALS AND METHODS: A total of 599 serum samples from HIV-positive patients attending our outpatient clinic during the last semester of 2000 were tested to assess the prevalence of HTLV co-infection in both Italian (n = 472) and non-European HIV-infected patients (n = 127). RESULTS: 72 samples were positive for HTLV-II. Most of the HTLV-II-positive patients were Italian (71/72, 98.6%) and 98.5% of them had acquired the HIV infection through use of intravenous recreational drugs. CONCLUSION: These data demonstrate a high HTLV-II exposure among HIV-positive intravenous drug users in our area which was not previously considered to be an area of endemicity for HTLV-II.

Adult↗
PubMed2003

Characterization of viro-immunological responses in a closely followed cohort of heavily pretreated patients: evidence from the GenPheRex Study.

OBJECTIVES: To assess prevalence and predictive factors of viro-immunological discordant trends in a cohort of heavily pretreated patients. METHODS: Factors associated with viro-immunological discordant trends either as categorical or continuous measures have been studied in 159 heavily pretreated HIV-positive patients from a multicentre prospective study of real- vs. virtual-phenotype. Univariate and multivariate logistic regressions were used to assess risk factors for categorical discordant responses, ceasing follow-up at week 32 since enough patients had been on the original drug combination for a sufficient amount of time to evaluate their immune response. Complementary linear regression analysis was performed over the entire 48 weeks' follow-up considering CD4 and plasma viral load (pVL) as continuous measures. RESULTS: Among 58 virological responder patients (> or =1 log10 HIV-1 RNA copies/mL decrease) and 101 virologically non-responders, immunological discordances (increase in CD4 count of< or > or =100 cells/microL) were observed in 58.6% and 38.6%, respectively. Baseline CD4 count was associated with discordant responses in both groups. Multivariable linear regression over the entire 48 weeks' follow-up demonstrated significant correlation between absolute decrease in pVL and increase in CD4 count (HR 28.06, 95%CI 35.32-20.79; P<0.001), also the use of protease inhibitors (PIs) in the salvage regimen (HR 36.57, 95%CI 15.45-57.68; P<0.001) and >8 months on treatment (HR 41.64, 95%CI 19.27-64.01; P<0.001) correlated with highly significant immune recovery. CONCLUSIONS: These data confirm that therapy, possibly including PIs, should be continued in heavily pretreated patients and that hard-to-reach pVL undetectability is not essential to obtain immunologic recovery; however, this is strongly increased by the degree of pVL reduction that should be achieved.

Anti-HIV Agents↗
PubMed2003

Antibiotic lock-technique for the treatment of catheter-related bloodstream infections.

The management of central venous catheter-related bloodstream infections (CRBSI), though still debated, requires the removal of the line in most cases: we investigated the efficacy of an alternative approach, based on higher concentrations of antibiotics locked within the catheter lumen, in an open, pilot study aimed at preserving the line in place and at eradicating the infection. Thirty consecutive patients carrying a central line over 10 days and who fulfilled criteria for ascertained diagnosis of bacterial CRBSI, had the catheter "locked" with antimicrobials therein; all patients also received systemic antibiotic therapy within the first 48 hours. Subsequently, 15 patients underwent locks alone, and 15 locks plus systemic therapy. Twenty-eight out of 30 (93.3%) patients retained the catheter in place, appearing to be cleared of infection and no treatment-related untoward events were observed. Locks should be considered as effective as line removal in the management of bacterial CRBSI in unselected patients, and could thus provide advantages in terms of resource sparing and lowered antibiotic pressure in the hospital setting.

Adult↗
PubMed2003

Clustering of tuberculosis among senegalese immigrants in Italy.

OBJECTIVE: To study clustered Mycobacterium tuberculosis isolates as an indicator of recent TB transmission in a small urban setting in Italy, and to determine associated risk factors. METHODS: M. tuberculosis strains isolated between 1991 and 1997 were characterised by IS6110 restriction fragment length polymorphism (RFLP) analysis. RESULTS: One hundred and ninety-five isolates were available for RFLP analysis, which revealed 163 different patterns. Available cases were represented by 137 Italians (70%), 32 Senegalese (17%), and 26 other foreign-born cases (13%). A unique fingerprint pattern was found in 143 cases (73.3%), while 52 strains (26.7%) were grouped into 20 clusters. Nineteen cases (10%) were resident in the same quarter of Brescia with a high density of Senegalese immigrants (Area A). An increased probability of yielding clustered M. tuberculosis strains was associated with residence in Area A (OR 3.87, 95%CI 1.42-10.56; P = 0.02) and being Senegalese (OR = 5.96, 95%CI 1.48-23.97; P = 0.005). In the logistic regression analysis, being Senegalese was independently associated with yielding a clustered M. tuberculosis strain. CONCLUSIONS: Our results demonstrate a clustering of TB cases among Senegalese immigrants and suggest that RFLP analysis may be used to identify geographical areas where efforts can be targeted to interrupt TB transmission.

Adult↗
PubMed2002

Management of hepatitis C in human immunodeficiency virus-infected patients.

Hepatitis C virus-related liver disease and its associated complications are steadily emerging health concerns in persons co-infected with human immunodeficiency virus. The increasing number of liver-related deaths in human immunodeficiency virus-hepatitis C virus co-infected individuals supports the compelling argument for more aggressive treatment in these patients. The safety and efficacy of interferon/ribavirin in human immunodeficiency virus/hepatitis C virus co-infected patients is currently under evaluation. Despite well-documented concern over highly active antiretroviral therapy-associated hepatotoxicity human immunodeficiency virus/hepatitis C virus co-infected patients should be offered antiretroviral therapy. Since management of co-infected patients is complex a multidisciplinary approach is needed in order to facilitate care and help patients to achieve a positive outcome.

Antiretroviral Therapy, Highly Active↗