Publications (49) View all
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Article: Factors associated with virological success with raltegravir-containing regimens and prevalence of raltegravir-resistance-associated mutations at failure in the ARCA database.
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ABSTRACT: Raltegravir (RAL) is the only licensed human immunodeficiency virus (HIV) integrase inhibitor. The factors associated with the virological response to RAL-containing regimens and the prevalence of integrase mutations associated with RAL failure deserve further investigation. From the Antiretroviral Resistance Cohort Analysis database, we selected triple-class-experienced subjects failing their current treatment with complete treatment history available. Selection criteria included HIV-RNA, CD4 count and HIV genotype within 3 months of RAL initiation. Factors associated with 24-week response were analysed; genotypic sensitivity scores (GSS) and weighted-GSS were evaluated. Virological response was achieved in 74.3% of 105 subjects. Mutations associated with RAL failure were detected in 12/24 subjects with an integrase genotype, with the prevalence of Q148H + G140S. Each extra unit of GSS (p 0.05, OR 2.62; 95% CI 1.00-6.87). was found to be a associated with response. Weighted-GSS had borderline statistical significance (p 0.063, OR 2.04; 95% CI 0.96-4.33) When stratifying for different cut-offs (<1 as reference, 1-1.49, ≥1.5), a borderline significant increase in the probability of response appeared for GSS ≥1.5 (p 0.053, OR 4.00; 95% CI 0.98-16.25). GSS ≥1 showed the highest sensitivity, 82.6%. Receiver operating characteristic curves depicted the widest area under the curve (0.663, p 0.054) of GSS ≥1. Unresponsiveness to RAL-containing regimens among triple-class-experienced subjects was low. The activity of the background regimen was strongly associated with response. Although few integrase genotypes were available at failure, half of these were without integrase resistance mutations. The substantial rate of RAL failure in the absence of known RAL-resistance mutations may be associated with adherence issues and this issue warrants further analysis in longer observations.Clinical Microbiology and Infection 01/2013; · 4.54 Impact Factor -
Article: HIV-HCV co-infection: epidemiology, pathogenesis and therapeutic implications.
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ABSTRACT: Hepatitis C virus (HCV) is the cause of more than three-quarters of liver-related deaths in HIV-seropositive individuals and it is remarkable that today approximately one-quarter of HIV-infected individuals in Europe and the USA have a HCV coinfection. HIV/HCV coinfected patients were more likely to develop cirrhosis, had an increased risk of developing AIDS, of HIV-related disease and of overall mortality. How HCV may affect the course of HIV infection is not well known even if it was suggested that HCV co-infection is able to increase immune activation and to sensitize CD4+ T-cells towards apoptosis in the absence of HIV therapy. There are many evidences that the simultaneous presence of HIV infection accelerates the liver damage from HCV favouring the evolution to cirrhosis in co-infected patients. HIV increasing of TNF alpha liver production and of HCV replication in peripheral blood lymphomonocytes are the mechanisms at the basis of this phenomenon. HAART had a positive effect on HIV/HCV co-infection, otherwise it does not appear to fully correct the adverse effect of HIV infection on HCV-related outcomes. Traditional treatment with pegilated Interferon plus ribavirin have low rates of sustained virological response in co-infected patients especially if infected with HCV genotype 1, and better results were often obtained in patients in which the use of antiretroviral treatment was avoided to reduce the occurrence of adverse effects. The recent preliminary results on the use of anti-HCV protease inhibitor drugs, boceprevir and telapravir, in co-infected people seems to demonstrate an enhanced antiviral efficacy in the HIV/HCV co-infected population of triple anti-HCV treatment even is some important limitation as interactions with antiretroviral agents and selection of HCV drug resistance, lead to consider the need for further studies designed to assess the best therapeutic strategies.European review for medical and pharmacological sciences 11/2012; 16(11):1473-83. · 1.04 Impact Factor -
Article: Long-term follow-up of HIV-infected patients in salvage therapy with raltegravir plus optimized background regimens: a multicentre Italian experience
Journal of the International AIDS Society 04/2012; 13:1-2. · 3.26 Impact Factor -
Article: Incidence and risk factors of major cardiovascular events in a multicentre HIV cohort.
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ABSTRACT: Cardiovascular (CV) [1] and cerebrovascular [2] events threaten HIV+ subjects, affecting them earlier as compared to the general population and the current algorithms seem inadequate to estimate the CV risk, in particular concerning the weight of drugs, immunity and virus-related inflammation as risk factors. We analysed three Italian HIV cohorts from January 2005 to August 2011, extracting cases of acute myocardial infarction (AMI) or stroke. We analysed at the time of the event the subjects' age, the risk factors, the Framingham score, the antiviral regimen and the time spent on each drug, the CDC stage, the nadir CD4+ T cells and the outcome. Out of 4893 patients 92 experienced major CV events (76 AMI and 19 stroke, 2 subjects having both) and 10 died, at a median age of 50 years (range 33-77). Classical risk factors were widely represented, mainly smoke (72.8%) and dyslipidemia (53.3%). Three young subjects had no risk factors and dramatic coronary patterns, leading in one case to transplantation. No one ever had pathological bone fractures, and only 4/81 had GFR <60 mL/min (range 33.6-57.4). The median 10 years' Framingham score was 10.5 (range 1-31). Abacavir had been taken by 19 subjects, equal to tenofovir and less than zidovudine (n=55), and lopinavir/ritonavir by 20, and no single drug emerged as risk. The median time spent on abacavir and/or on lopinavir/ritonavir was 48 weeks (range 1-552) and 106 weeks (range 8-256), respectively. One patient was antiretroviral-naïve. The CD4 nadir was 183/mm(3) and 41.3% were CDC stage C. Although infrequent (1.8%), major CV events affect HIV people at younger age. Classical risk factors are common, while no drug effect emerged clearly. HIV infection was managed late in most of the patients. Early initiation of HAART [3] and reduction of risk factors seem the key points for preventing the occurrence of CV disease.Journal of the International AIDS Society 01/2012; 15(6):18272. · 3.26 Impact Factor -
Article: Update on emergence of HIV-1 resistance to antiretroviral drug classes in an Italian national database: 2007-2009.
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ABSTRACT: We analysed trends of human immunodeficiency virus type 1 (HIV-1) drug resistance during 2007-2009 in the Italian national HIV drug resistance database 'ARCA'. Prevalence of resistance in each year was examined on the basis of the presence of major International AIDS Society-2009 mutations. Predictors of resistance were analysed by multivariable logistic regression. Nine hundred and sixty-six patients were selected. Resistance to nucleoside reverse transcriptase inhibitors and protease inhibitors showed a significant decline with respect to previous surveys. Resistance to any class of drug and three drug classes remained stable. Independent predictors of three-class resistance were the number of treatment regimens experienced, prior suboptimal nucleoside reverse transcriptase inhibitor therapy and the current use of ritonavir-boosted protease inhibitors.Clinical Microbiology and Infection 04/2011; 17(9):1352-5. · 4.54 Impact Factor
