Publications by authors named "Raffaella Rosso"

36 Publications

Pharmacokinetics of lopinavir determined with an ELISA test in youths with perinatally acquired HIV.

Indian J Pediatr 2014 Sep 7;81(9):856-60. Epub 2013 Sep 7.

Infectious Diseases Clinic, San Martino Hospital, University of Genoa, Genoa, Italy.

Objective: To investigate the plasma levels of lopinavir by enzyme-linked immunosorbent assay (ELISA) in a cohort of patients who were vertically infected with human immunodeficiency virus 1 (HIV).

Methods: Plasma levels of lopinavir (Cmin) were determined by ELISA test in patients treated with lopinavir/ritonavir-based combined antiretroviral therapy who had achieved virological response after 4 wk of therapy. Reference lopinavir concentrations were Cmin 1-8 μg/mL. Correlation between lopinavir plasma concentration and continuous variables was evaluated by mean of Pearson correlation coefficient. Differences in lopinavir (LPV) concentration for binary categorical variables were assessed by Mann-Whitney test, while for variables with more than two categories Kruskal-Wallis test was used.

Results: Thirty-four patients were enrolled; median age was 133 mo (15-265). The median lopinavir dose tested was 383.5 mg/kg (IQR: 266.6-400 mg/kg), with a median plasma concentration of 8.8 μg/mL (IQR: 5-14 μg/mL). Lopinavir Cmin was <1 μg/mL in only one sample (2.9 %), while 14 samples had Cmin between 1 and 8 μg/mL (41.2 %) and 19 (55.9 %) > 8 μg/mL. No significant correlations were found between plasma concentrations of lopinavir and the continuous variables considered in the study. A negative but, not completely significant, correlation was found between plasma drug concentration and body mass index (r = -0.29; p = 0.09).

Conclusions: The use of a simple and relatively cost-effective methodology might render therapeutic drug monitoring (TDM) appeal in the daily clinical practice.
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http://dx.doi.org/10.1007/s12098-013-1198-1DOI Listing
September 2014

Inflammation markers correlate with common carotid intima-media thickness in patients perinatally infected with human immunodeficiency virus 1.

J Ultrasound Med 2013 May;32(5):763-8

Infectious Disease Clinic, University of Genoa, San Martino Hospital, Genoa, Italy.

Objectives: To investigate common carotid intima-media thickness in a cohort of patients who were vertically infected with human immunodeficiency virus 1 (HIV-1).

Methods: We conducted a cross-sectional observational study. Human immunodeficiency virus 1-infected patients were compared with age-, sex-, and body mass index-matched healthy participants. Common carotid intima-media thickness was measured in all participants on both sides of the neck, and the mean intima-media thickness was calculated. Metabolic parameters and markers of inflammation were measured only in HIV-1-infected patients. Statistical analysis was performed by multiple regression and by a matrix of Pearson correlation coefficients. The Student t test was used to compare mean common carotid intima-media thickness values between groups.

Results: Forty patients (21 female) with HIV-1 infection acquired from birth with a mean age ± SD of 16.3 ± 4.7 years and 27 healthy participants (11 female) with a mean age of 17.7 ± 4.6 years were included in the study. Mean common carotid intima-media thickness in the HIV-1-infected group (0.450 ± 0.088 mm) was significantly higher (P < .05) than in the control group (0.407 ± 0.079 mm). No significant association was found between intima-media thickness and a specific antiretroviral regimen, exposure to combined antiretroviral agents, and HIV status. In multiple regression analyses, higher levels of insulin (P= .007) and elevated levels of glycated hemoglobin (P= .01) were associated with intima-media thickness changes.

Conclusions: Patients perinatally infected with HIV have increased common carotid intima-media thickness compared with healthy individuals. These changes were more pronounced with increasing age and inflammation markers. Interventions that improve cardiovascular risk profiles should be considered in HIV-infected young adults.
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http://dx.doi.org/10.7863/ultra.32.5.763DOI Listing
May 2013

Antiretroviral use in Italian children with perinatal HIV infection over a 14-year period.

Acta Paediatr 2012 Jul 4;101(7):e287-95. Epub 2012 Apr 4.

Department of Science for Woman and Child Health, University of Florence, Italy.

Background: Information on the use of new antiretroviral drugs in children in the real setting of clinical fields is largely unknown.

Methods: Data from 2554 combined antiretroviral therapy (cART) regimens administered to 911 children enrolled in the Italian Register for HIV infection in children, between 1996 and 2009, were analysed. Factors potentially associated with undetectable viral load and immunological response to cART were explored by Cox regression analysis.

Results: Proportion of protease inhibitor (PI)-based regimens significantly decreased from 88.0% to 51.2% and 54.9%, while proportion on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens increased from 4.5% to 38.8% and 40.2% in 1996-1999, 2000-2004 and 2005-2009, respectively (p < 0.0001). Significant change in the use of each antiretroviral drug occurred over the time periods (p < 0.0001). Factors independently associated with virological and immunological success were as follows: later calendar periods, younger age at regimen (only for virological success) and higher CD4(+) T-lymphocyte percentage at baseline. Use of unboosted PI was associated with lower adjusted hazard ratio (aHR) of virological or immunological success with respect to NNRTI- and boosted PI-based regimens, with no difference among these two latter types.

Conclusion: Use of new generation antiretroviral drugs in Italian HIV-infected children is increasing. No different viro-immunological outcomes between NNRTI- and boosted PI-based cART were observed.
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http://dx.doi.org/10.1111/j.1651-2227.2012.02675.xDOI Listing
July 2012

Effects of hepatitis C virus infection on the pharmacokinetics of ritonavir-boosted atazanavir in HIV-1-infected patients.

J Infect Chemother 2012 Aug 16;18(4):587-90. Epub 2012 Mar 16.

Department of Infectious Diseases, San Martino Hospital Genoa, University of Genoa, Largo Rosanna Benzi, 10, 16132, Genoa, Italy.

Most antiretrovirals are metabolized in the liver, and overexposure could be more common in human immunodeficiency virus (HIV)-infected patients with hepatic impairment. Careful monitoring of potential drug-related liver injury in clinical practice is necessary. The aim of our study was to analyze the trough concentrations (C (trough)) of atazanavir (ATV) in the plasma of HIV/hepatitis C virus (HCV)-co-infected patients and to compare the values with those of a HIV-infected control population. C (trough) values (22-26 h after last intake) of atazanavir, following the administration of atazanavir/ritonavir 300/100 mg once daily as part of antiretroviral therapy, were assessed by HPLC. We also collected data on dosing of atazanavir, and on demographic (age, gender, and ethnicity), physiological (weight and body mass index), and clinical parameters (CD4+ cell count, HIV-RNA viremia, co-medication, and hepatitis C co-infection). A total of 28 Caucasian HIV-infected adults were studied, of whom 13 were HIV/HCV co-infected. No baseline characteristics differed between the two cohorts, except statistically significant differences regarding ALT, AST, and total bilirubin. The median (range) plasma ATV C (trough) levels were 0.62 (0.05-3.22) μg/ml in HIV patients and 0.32 (0.04-3.37) μg/ml in HIV/HCV patients. Thus, there was no significant difference in plasma trough levels of atazanavir in the two cohorts. In our patients with mild impairment of hepatic function caused by HCV infection, atazanavir C (trough) was comparable in HIV-infected and HIV/HCV-co-infected patients.
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http://dx.doi.org/10.1007/s10156-012-0402-yDOI Listing
August 2012

Pharmacokinetics and short-term safety and tolerability of etravirine in treatment-experienced HIV-1-infected children and adolescents.

AIDS 2012 Feb;26(4):447-55

Department of Pediatrics and Adolescent Medicine, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.

Objectives: To evaluate the pharmacokinetics, weight-based dose selection and short-term safety and tolerability of etravirine in HIV-1-infected children and adolescents.

Design: Phase I, nonrandomized, open-label study in two stages.

Methods: Children and adolescents aged at least 6 years to 17 years or less on a stable lopinavir/ritonavir-based antiretroviral regimen with HIV-1 RNA plasma viral load less than 50 copies/ml were enrolled. In both stages, etravirine (4 mg/kg twice daily in stage I, 5.2 mg/kg twice daily in stage II), added to the existing antiretroviral regimen, was administered for 7 days followed by a morning dose and 12-h pharmacokinetic assessment on day 8. Pharmacokinetic parameters were determined using noncompartmental analysis. Data were compared with those previously established in HIV-1-infected adults on a similar etravirine (200 mg twice daily) combination antiretroviral regimen.

Results: Twenty-one patients were recruited to each stage; 19 and 20 had evaluable pharmacokinetics in stages I and II, respectively. Mean (SD) maximum plasma concentrations in stages I and II were 495 (453) and 757 ng/ml (680), respectively; area under the plasma concentration-time curve over 12 h was 4050 (3602) and 6141 ng h/ml (5586), respectively. Statistical/qualitative comparisons showed comparable exposures with adults in stage II; however, the upper 90% confidence interval fell outside the predefined range. Plasma viral load remained undetectable on day 8 in all patients, and etravirine was well tolerated at both doses.

Conclusion: Etravirine 5.2 mg/kg was well tolerated in this study and this dose was selected for further investigation in clinical trials.
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http://dx.doi.org/10.1097/QAD.0b013e32834f30b1DOI Listing
February 2012

Nevirapine-based regimens in routine clinical settings: results from a large Italian cohort of HIV-1 infected adults.

Curr Drug Saf 2011 Jul;6(3):138-44

Department of Internal Medicine and Infectious Diseases, "San Martino" Hospital, Genoa, Italy.

Unlabelled: We assessed the safety and efficacy of different nevirapine-based regimens in patients starting this drug in a large cohort of Caucasian subjects during the 1999-2007 periods.

Methods: A retrospective database review of all patients receiving nevirapine was performed; clinical, biochemical (hepatic and metabolic profiles), immuno-virological parameters were evaluated in the overall population and in different subgroups (according to gender, therapy-experience and HBV/HCV co-infection). We determined risk factors related to dyslipidemia development and to nevirapine interruption within 1 year.

Results: We evaluated 277 patients; 58 (20.9%) were naïve, 180 (65%) females and 137 (49.5%) HBV/HCV co-infected. After 48 weeks, 73.6% patients continued antiretroviral regimens. Among these, nevirapine showed little hepatic and metabolic impact, as well as good immuno-virological outcome despite sex, drug experience and co-infection. Factors related to development of dyslipidemia were higher in total cholesterol, female gender with high CD4 count and male gender with low CD4 count (p<0.05). Factors related to discontinue nevirapine were age and HBV/HCV co-infection (p<0.05).

Conclusions: We observed a high rate of discontinuation probably because of the special composition of our population (huge proportion of women and co-infected individuals). Nevertheless, nevirapine was a well-tolerated drug with a favorable impact on hepatic, metabolic and immuno-virological parameters in all the analyzed subgroups.
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http://dx.doi.org/10.2174/157488611797579339DOI Listing
July 2011

Lamivudine resistance mutations in European patients with hepatitis B and patients co-infected with HIV and hepatitis B.

J Med Virol 2011 Nov;83(11):1905-8

Infectious Diseases Department, San Martino Hospital and University of Genoa, Genoa, Italy.

Evaluation of resistance pattern in patients with chronic hepatitis B. Retrospective study of hepatitis B virus (HBV) resistance mutations in patients found viraemic after first-line treatment. HBV viral load was determined by a real-time polymerase chain reaction and the substitutions in HBV-DNA were studied by polymerase sequencing test. First line treatment had failed in 12 out of 33 patients (36%) receiving anti-HBV drugs. The 12 patients with persistent viraemia were all lamivudine (LAM) experienced and 7 had a polymerase sequencing test available. LAM substitution mutations L180M + M204V/I were found in six out of seven cases, with an accompanying V173L mutation in three cases. These mutations were also related with changes in HBsAg. The use of potent drugs in the first line anti-HBV therapy may reduce the resistance mutations in the future.
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http://dx.doi.org/10.1002/jmv.22192DOI Listing
November 2011

Patient-reported outcomes and low-level residual HIV-RNA in adolescents perinatally infected with HIV-1 after switching to one-pill fixed-dose regimen.

AIDS Care 2012 29;24(1):54-8. Epub 2011 Jul 29.

Clinica Malattie Infettive, Ospedale San Martino, Università degli Studi di Genova, Genova, Italy.

The choice of an antiretroviral regimen can often impact on adherence, treatment satisfaction and therefore influence on clinical outcome. These concerns are particularly true in adolescents. In this setting, adherence is usually affected by multifactor events and biopsychosocial factors, which connect and changeover time. We evaluated the effect of a switch to a single-pill fixed-dose regimen on patient-reported outcomes, virologic and immunologic outcomes, and safety in a cohort of adolescents with perinatal HIV-1 infection. In addition, we evaluated the effect on low-level residual HIV-RNA. An open-label, non-randomised study was performed: 12 adolescents with a confirmed viremia <50 copies/mL treated with lamivudine or emtricitabine, tenofovir and efavirenz were switched to one-pill fixed-dose regimen of emtricitabine/tenofovir/efavirenz. At the end of follow-up, the new regimen was associated with improvements in treatment satisfaction, HIV-symptoms, whereas adherence remained high. No immunological or virological significative changes were observed. No side-effects were registered. Moreover, the low-level residual HIV-RNA was <3 copie/mL in all patients. One-pill fixed-dose regimen is an added value that favours adherence, reduces HIV-symptoms, improves patients' satisfaction and could better control of HIV-RNA in adolescents, too.
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http://dx.doi.org/10.1080/09540121.2011.596511DOI Listing
May 2012

HIV and accelerated atheroprogression: role of antiretroviral therapy.

Curr Pharm Biotechnol 2012 Jan;13(1):88-96

Clinica Malattie Infettive, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy.

The introduction of effective and potent treatments for human immunodeficiency virus (HIV) infection resulted in prolonged survival and better quality of life of HIV-infected patients. However, the longer survival and the anti-HIV medication side effects caused the emergence of new clinical issues, such as the increase in cardiovascular risk, favored by multiple factors, partly related to HIV infection itself, partly to the anti-HIV molecules. HIV infection itself may affect cardiovascular risk through chronic inflammation induced by uncontrolled viral replication, whereas long-term antiretroviral therapy may increase the cardiovascular risk through several mechanisms. Thus, due to the multiple and conflicting causes of cardiovascular disorders in HIV-infected patients, clinicians should take into consideration all modifiable risk factors, in order to implement an effective prevention of this clinical issue.
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http://dx.doi.org/10.2174/138920112798868520DOI Listing
January 2012

Osteonecrosis in human immunodeficiency virus (HIV)-infected patients: a multicentric case-control study.

J Bone Miner Metab 2011 May 22;29(3):383-8. Epub 2011 Jan 22.

Unità di Malattie Infettive, Ospedale Civile Spirito Santo, Via C. Barbella 10, 65126 Pescara, Italy.

Osteonecrosis (ON) is a rare disabling complication occurring in patients with human immunodeficiency virus (HIV) infection at a higher frequency than in the general population despite effective combination antiretroviral therapy being made available, as recently documented by several retrospective studies. We designed a multicentric case-control study among HIV-infected patients cared for at institutions in the Italian CISAI group (Italian Study Group for Adverse Events in HIV Infection) to search for additional predictors of ON in this special population. All centers which observed at least one case of ON were requested to report data for central re-evaluation. Parallel HIV-positive, ON-free controls were randomly selected and matched with confirmed cases of ON for sex, age and CD4 T-cell counts at the time of HIV diagnosis. Fifteen cases and controls were included in the final sample. Univariate statistical analyses revealed a significant association between ON and exposure to steroids (P = 0.001), exposure to one or more drugs in addition to HAART (Highly Active Anti-Retroviral Therapy) (P = 0.03), high titers of total serum IgE (P = 0.02), loss of working ability (P = 0.03), triglycerides levels over 200 mg/dL before antiretrovirals (P = 0.03) and cholesterol levels over 200 mg/dL before and after antiretrovirals (P = 0.03 and 0.05, respectively). High serum IgE levels and loss of working ability in advance of ON appeared for the first time as possible predictors of ON in HIV patients, while long-term exposure to steroids, combined hyperlipemia and chronic treatment with other drugs in addition to antiretrovirals were confirmed. Predicting and preventing ON in the individual HIV-infected patient is therefore a clinically challenging opportunity.
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http://dx.doi.org/10.1007/s00774-010-0245-5DOI Listing
May 2011

Safety and efficacy of pegylated interferon and ribavirin in adolescents with human immunodeficiency virus and hepatitis C virus acquired perinatally.

J Med Virol 2010 Jul;82(7):1110-4

Infectious Diseases Clinic, University of Genoa, San Martino Hospital, Genoa, Italy.

Limited evidence is available currently regarding the efficacy and safety of pegylated interferon (PEG-IFN) and ribavirin in patients co-infected perinatally with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). No information is available on whether or not these patients should be treated earlier for infection with HCV. This report describes four patients with HIV and HCV co-infection acquired perinatally, who were treated with PEG-IFN and ribavirin for chronic viral hepatitis caused by HCV.
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http://dx.doi.org/10.1002/jmv.21802DOI Listing
July 2010

Whole body bone scintigraphy in tenofovir-related osteomalacia: a case report.

J Med Case Rep 2009 Jul 22;3:8136. Epub 2009 Jul 22.

Introduction: Tenofovir disoproxil fumarate (Viread((R))) is the only nucleotide reverse transcriptase inhibitor currently approved for the treatment of HIV. It is frequently prescribed not only for its efficacy but also for its decreased side effect profile compared with other nucleotide analogs. In addition, it is now increasingly recognized as a cause of acquired Fanconi's syndrome in individuals with HIV.

Case Presentation: We describe a 48-year-old woman infected with HIV, with chronic renal insufficiency, who developed Fanconi's syndrome after inclusion of tenofovir disoproxil fumarate in her antiretroviral therapy. A whole body bone scintigraphy was performed, revealing an abnormal distribution of radiotracer uptake, with characteristic changes compatible with osteomalacia. All symptoms disappeared after tenofovir discontinuation and mineral supplementation. No other explanation for the sudden and complete resolution of the bone disease was found.

Conclusion: The case highlights the role of whole body bone scintigraphy in the diagnosis of tenofovir-related osteomalacia.
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http://dx.doi.org/10.4076/1752-1947-3-8136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737799PMC
July 2009

Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy.

BMC Infect Dis 2009 Aug 26;9:140. Epub 2009 Aug 26.

Department of Pediatrics, University of Florence, Florence, Italy.

Background: Early highly active antiretroviral therapy (HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking.

Methods: We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range [IQR]:4.21-7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided.

Results: Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71-5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4+ T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4+ T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001).

Conclusion: Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed.
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http://dx.doi.org/10.1186/1471-2334-9-140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753343PMC
August 2009

Evaluation of insulin resistance in a cohort of HIV-infected youth.

Curr Diab Rep 2009 Aug;9(4):260-1

Infectious Diseases Clinic, University of Genoa, San Martino Hospital, 16132 Genova, Italy.

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http://dx.doi.org/10.1007/s11892-009-0052-3DOI Listing
August 2009

Efficacy and safety of darunavir and etravirine in an antiretroviral multi-experienced youth with vertically HIV-1 infection.

Eur J Med Res 2009 Mar;14(3):136-8

Department of Infectious Diseases, University of Genoa, San Martino Hospital, Genova, Italy.

Multiclass-drug resistance, often caused by poor treatment compliance, is a challenging problem in all categories of HIV-infected patients. Selective pressure is higher in youth for both biological and behavioral reasons. We report the case of a 15-year-old Caucasian male, with vertically acquired HIV-1 infection, who failed several lines of antiretroviral therapy and was successfully treated with darunavir/ritonavir and etravirine.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352063PMC
http://dx.doi.org/10.1186/2047-783x-14-3-136DOI Listing
March 2009

Infectious complications of cancer chemotherapy in HIV patients.

Curr Infect Dis Rep 2008 May;10(2):149-56

Infectious Diseases Clinic, University of Genoa, San Martino Hospital, Largo R. Benzi 10, 16132, Genoa, Italy.

The outcome for HIV-infected patients with cancer has dramatically improved in the highly active antiretroviral therapy (HAART) era, probably due to improvements in immune status and bone marrow function that allow the possibility of increased drug-dose intensity with a higher complete remission rate. Although data regarding the optimal management of these cancers are lacking, current studies suggest that patients with HIV-associated malignancies could be treated using approaches similar to those for their counterparts in the general population (ie, with chemotherapy, radiation, and appropriate use of supportive measures). In the HAART era, the AIDS-related mortality rate has decreased by approximately 70%, and so the cause of the growing number of reports of cancers in HIV patients is unclear. Clearly, non-AIDS-defining malignancies account for more morbidity and mortality than AIDS-defining malignancies. Prevention strategies are needed to adequately deal with HIV-associated cancers in an aging and growing HIV-positive population.
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http://dx.doi.org/10.1007/s11908-008-0026-7DOI Listing
May 2008

Effects of the change from Stavudine to tenofovir in human immunodeficiency virus-infected children treated with highly active antiretroviral therapy: studies on mitochondrial toxicity and thymic function.

Pediatr Infect Dis J 2008 Jan;27(1):17-21

Infectious Diseases Clinics, San Martino Hospital, University of Genoa, Genoa, Italy.

Background: Changing from drugs that have significant mitochondrial toxicity to less toxic compounds may be of benefit in human immunodeficiency virus (HIV)-positive patients who receive highly active antiretroviral therapy. Few data on mitochondrial toxicity of antiviral drugs are available in HIV-positive children.

Methods: Eighteen HIV-positive children (median age, 10.9 years) receiving a stavudine-containing regimen were randomized to maintain stavudine (arm A) or change to tenofovir (arm B), while preserving the remaining drugs. Glucose, lipidic, and viro-immunologic factors were assessed at months 0, 1, 3, 6, 12, and 18. Thymic output and mtDNA content were measured in peripheral blood mononuclear cells at 0 and 6 months, mtDNA in isolated CD4+ and CD8+ T cells after 18 months.

Results: From baseline to month 6, arms A and B showed similar thymic output and mtDNA. After 18 months, a significant decrease in plasma HDL was observed in arm B, along with a small increase in blood glucose; mtDNA showed no difference. In the 2 arms other factors did not show significant differences from the baseline and from the previous values at 18 months.

Conclusions: Changing from stavudine to tenofovir was well-tolerated, and viro-immunologic success was maintained.
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http://dx.doi.org/10.1097/INF.0b013e31814689beDOI Listing
January 2008

Evaluation of insulin resistance in a cohort of HIV-infected youth.

Eur J Endocrinol 2007 Nov;157(5):655-9

Department of Infectious Diseases, San Martino Hospital, University of Genoa, Largo R. Benzi 10, 16132 Genoa, Italy.

Objective: Metabolic abnormalities, including impairment of glucose homeostasis, have been well characterized in HIV-infected patients. In contrast to adults, insulin resistance and diabetes mellitus appear to be relatively uncommon finding in youth.

Design: We assessed insulin resistance, and associated risk factors, in a population of vertically HIV-infected children and young adults, when compared with a control population of healthy children.

Methods: At the time of enrolment, weeks of pregnancy, birth weight, sex, age, weight, height, body mass index (BMI), pubertal stages, CDC classification, blood pressure, clinical lipodystrophy, hepatitis B or C co-infection, antiretroviral therapy, CD4 T lymphocyte counts, and HIV-RNA levels were recorded. Fasting plasma glucose and insulin levels and homeostatic model assessment-insulin resistance (HOMA-IR) were determined. These parameters were compared between HIV patients and healthy controls with multivariate analyses.

Results: Fasting insulin levels (OR=1.21, P<0.001) and glycemia (OR=0.89, P<0.001) were significantly different between HIV-infected patients and controls. Antiretroviral therapy duration (r=0.281, P<0.05), triglyceride levels (r=0.286, P<0.05), age (r=0.299, P<0.05), and BMI SDS (r=0.485, P<0.001) were significant predictor variables of insulin resistance, expressed as HOMA-IR. Moreover, clinical lipodystrophy seems to be strongly correlated to glycemia (P<0.05), triglyceride levels (P<0.05), serum insulin levels (P<0.001), HOMA-IR (P<0.05), and also with therapy duration (P<0.05).

Conclusions: Both HIV infection and antiretroviral therapy demonstrate differential effects on glucose metabolism in HIV-infected children. Targeted prevention of insulin resistance and diabetes mellitus in HIV-infected children and young adults is needed in order to avoid the associated long-term complications that would otherwise occur, given the improvement in life expectancy of HIV-infected individuals.
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http://dx.doi.org/10.1530/EJE-07-0414DOI Listing
November 2007

Changing patterns of clinical events in perinatally HIV-1-infected children during the era of HAART.

AIDS 2007 Jul;21(12):1607-15

Department of Paediatrics, University of Florence, Via Luca Giordano 13, I-50132 Florence, Italy.

Background: The introduction of HAART has decreased mortality and progression to AIDS in perinatally HIV-1-infected children, but information on modification of the rate of specific clinical events is limited.

Method: An observational population study on changes in HIV-1-related morbidity was conducted on 1402 perinatally HIV-1-infected children enrolled in the Italian Register for HIV Infection in Children and prospectively followed in the pre-HAART (1985-1995) and post-HAART periods (1996-2000, and 2001-2005). Of this group, 773 children (55.1%) were followed from birth. Median observation time was 8.58 years (interquartile range, 3.71-13.72).

Results: Overall, 666 (47.5%) children developed AIDS and 420 (29.9%) died. Improved survival over time was evidenced at Kaplan-Meier analysis (P < 0.0001). Poisson regression analysis indicated that Centers for Disease Control and Prevention class B and C clinical event rates and most of the HIV-1-related organ complication rates significantly decreased starting from 1996-2000. Significant reductions in rates of cancer and opportunistic infections were evidenced after 2000. Nevertheless, opportunistic infections still occurred at high rates (6.09/100 person-years) in 2001-2005, with high rate of bacterial infections (3.55/100 person-years), particularly pneumonia (1.66/100 person-years), in this period. CD4 cell percentage was > 15% in 58.5% children with pneumonia.

Conclusions: Progressive reductions of both mortality and rates of class B and C clinical events, including organ complications, were evidenced in the HAART era. Nevertheless, severe bacterial infections, particularly pneumonia, still occurred at considerable high rates, even in the absence of a severe CD4 cell depletion.
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http://dx.doi.org/10.1097/QAD.0b013e32823ecf5bDOI Listing
July 2007

Efficacy of ertapenem in the treatment of early ventilator-associated pneumonia caused by extended-spectrum beta-lactamase-producing organisms in an intensive care unit.

J Antimicrob Chemother 2007 Aug 31;60(2):433-5. Epub 2007 May 31.

Infectious Diseases Division, San Martino University Hospital, Genoa, Italy.

Objectives: Ventilator-associated pneumonia (VAP) is a frequent complication of patients admitted to intensive care units (ICUs). Ertapenem is a newer carbapenem with good in vitro activity against extended-spectrum beta-lactamase (ESBL)-producing organisms. However, there are no clinical data to support the use of ertapenem in VAP. Our purpose is to evaluate the usefulness and safety of ertapenem in the treatment of VAP caused by susceptible ESBL strains.

Methods: Ertapenem 1 g daily intravenously was given to adult patients with signs and symptoms of VAP beginning within 7 days of mechanical ventilation and caused by ESBL-producing Gram-negative organisms.

Results: From June 2005 to June 2006, we enrolled 20 adult patients hospitalized in an ICU and diagnosed with VAP due to Gram-negative ESBL strains. Causative organisms identified as ESBL producers susceptible to ertapenem were Klebsiella pneumoniae (alone in 10 cases and with methicillin-resistant Staphylococcus aureus in 4 cases), Enterobacter cloacae (2), Proteus mirabilis (2) and Citrobacter freundii (2). Clinical success was achieved in 16/20 (80%) of the clinically evaluable patients and in 15/20 (75%) of the microbiologically evaluable patients. The drug was well-tolerated; one patient presented a transient increase in liver enzymes.

Conclusions: We believe this is one of the first reports to demonstrate that ertapenem has clinical utility in treating serious infections caused by ESBL-producing organisms. Ertapenem appears to be suitable for ESBL VAP therapy. This pilot study suggests subsequent controlled randomized trials in this indication.
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http://dx.doi.org/10.1093/jac/dkm180DOI Listing
August 2007

A randomized controlled trial of genotypic HIV drug resistance testing in HIV-1-infected children: the PERA (PENTA 8) trial.

Antivir Ther 2006 ;11(7):857-67

MRC Clinical Trials Unit, London, UK.

Objective: To evaluate the longer-term utility of genotypic resistance testing in HIV-1-infected children with virological failure.

Methods: Children aged 3 months-18 years switching antiretroviral therapy (ART) with HIV-1 RNA > 2,000 copies/ml were randomized between genotypic testing (Virtual Phenotype) and no testing at baseline and subsequent virological failures. Children were followed to at least 96 weeks.

Results: One hundred and seventy eligible children, from 24 clinical centres in six countries, were randomized to resistance testing (n = 87) or no testing (n = 83) between June 2000-July 2003. At baseline, mean HIV-1 RNA and CD4+ T-cell percentage were 4.7 log10 copies/ml and 20%, respectively. Children had taken ART for a mean of 5 years; 24% had received all three classes, 53% nucleoside reverse transcriptase inhibitors (NRTIs)+protease inhibitors (PIs), 9% NRTIs+non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 14% NRTIs only. There was no difference between the arms in the drug classes or the individual PIs/NNRTIs prescribed. However, 49% in the resistance test arm (RT) versus 19% in the no-test arm (NT) continued at least one NRTI from their failing regimen; 56% versus 19% were prescribed didanosine+stavudine as their NRTI backbone. Adjusting for baseline HIV-1 RNA, mean reductions in HIV-1 RNA at 48 weeks were 1.51 log10 copies/ml in the RT arm and 1.23 in the NT arm (P = 0.3); the difference between the arms was smaller at week 96 (RT: 1.50, NT: 1.47; P = 0.9).

Conclusion: In this first paediatric trial of resistance testing, we observed a substantial difference in NRTI-prescribing behaviour across arms. However statistically significant evidence of a long-term virological or immunological benefit was not observed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN14367816.
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March 2007

Cancer rates after year 2000 significantly decrease in children with perinatal HIV infection: a study by the Italian Register for HIV Infection in Children.

J Clin Oncol 2007 Jan;25(1):97-101

Department of Pediatrics, University of Florence, Florence, Italy.

Purpose: To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period.

Patients And Methods: An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%.

Results: Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004).

Conclusion: Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.
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http://dx.doi.org/10.1200/JCO.2006.06.6506DOI Listing
January 2007

Candida infections in the intensive care unit: epidemiology, risk factors and therapeutic strategies.

Expert Rev Anti Infect Ther 2006 Oct;4(5):875-85

Clinica Malattie Infettive, A.O. U. San Martino, R. Benzi 10 16132, Genoa, Italy.

This article reviews the epidemiology, predisposing risk factors and outcome of systemic Candida spp. infections in the intensive care unit setting. Incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years; while diagnosis of serious Candida infection may be difficult, the clinical conditions which predispose patients to these infections are now better understood and effective antifungal therapies are becoming increasingly available. Severe fungal infections are generally associated with poor outcomes in these patients. Patients at highest risk for Candida infection may be potential candidates for early, presumptive therapy. In this article we review antifungal treatment, including the use of polyenes, azoles and echinocandines, and the role of prophylaxis.
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http://dx.doi.org/10.1586/14787210.4.5.875DOI Listing
October 2006

Benign lymphoepithelial parotid lesions in vertically HIV-infected patients.

AIDS Patient Care STDS 2006 Aug;20(8):536-41

Department of Infectious Diseases, DICMI, University of Genoa, San Martino Hospital, Genoa, Italy.

Benign lymphoepithelial parotid lesions (BLL) are frequently reported in HIV-infected patients, although their clinical and prognostic significance in HIV infection has not been clearly defined. Ultrasonography (USG) has been shown to be a reliable method in monitoring the progression of such lesions. The purpose of this study was to describe the spectrum of sonographic and Doppler findings and to monitor any clinically evident physical change of parotid glands in a cohort of congenitally HIV-infected patients taking antiretroviral therapy. USG findings-based on their severity-have been grouped in three different patterns (0, 1, 2). Our cohort consisted of 51 patients with HIV in various Centers for Disease Control (CDC) stages and being given different antiretroviral protocols. The median USG follow-up was 36 months. The most frequent USG pattern was aspecific parotid gland enlargement (type 0, 45,1%). Patients with either lower CD4+ % (p < 0.20) and higher absolute and percent CD8+ cell count (p < 0.001 and p < 0.003) presented more frequently a type 2 USG pattern. None of them had any symptoms ascribed to "sicca syndrome" and only one patient developed non-Hodgkin's lymphoma during the follow-up, although his USG pattern at baseline was type 0. In summary, the spectrum of USG findings of BLL in vertically HIV-infected patients is broad. Because of the reported, although rare, possible malignant transformation of BLL in HIV-infected children, it is advisable to perform-even in asymptomatic patients-USG at least once per year or in concomitance with any physical modification of the parotid lesions.
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http://dx.doi.org/10.1089/apc.2006.20.536DOI Listing
August 2006