Raffaella Rosso

Epidemiological trends in nosocomial candidemia in intensive care

BackgroundInfection represents a frequent complication among patients in Intensive Care Units (ICUs) and mortality is high. In particular, the incidence of fungal infections, especially due to Candida spp., has been increasing during the last years.MethodsIn a retrospective study we studied the etiology of candidemia in critically ill patients over a five-year period (1999–2003) in the ICU of the San Martino University Hospital in Genoa, Italy.ResultsIn total, 182 episodes of candidaemia were identified, with an average incidence of 2.22 episodes/10 000 patient-days/year (range 1.25–3.06 episodes). Incidence of candidemia increased during the study period from 1.25 in 1999 to 3.06/10 000 patient-days/year in 2003. Overall, 40% of the fungemia episodes (74/182) were due to C.albicans, followed by C. parapsilosis(23%), C.glabrata (15%), C.tropicalis (9%) and other species (13%). Candidemia due to non-albicans species increased and this was apparently correlated with an increasing use of azoles for prophylaxis or empirical treatment.ConclusionThe study demonstrates a shift in the species of Candida causing fungemia in a medical and surgical ICU population during a 5 year period. The knowledge of the local epidemiological trends in Candida species isolated in blood cultures is important to guide therapeutic choices.

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

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.

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

BackgroundEarly 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.MethodsWe 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.ResultsNineteen 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).ConclusionOur 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.

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

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.

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

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.

Cancer Rates After Year 2000 Significantly Decrease in Children With Perinatal HIV Infection: A Study by the Italian Register for HIV Infection in Children

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.

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

IntroductionTenofovir disoproxil fumarate (Viread®) 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 Fanconis syndrome in individuals with HIV.Case presentationWe describe a 48-year-old woman infected with HIV, with chronic renal insufficiency, who developed Fanconis 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.ConclusionThe case highlights the role of whole body bone scintigraphy in the diagnosis of tenofovir-related osteomalacia.

Risk factors for chronic kidney disease among human immunodeficiency virus-infected patients: A European case control study.

OBJECTIVES Renal dysfunction is a common complication in human immunodeficiency virus (HIV)-infected patients and can be attributed to direct viral damage, comorbidities or drug toxicity. The aim of this study was to assess cross-sectional correlates of renal damage in a contemporary European cohort of patients. METHODS We performed a case-control study from our cohort of 750 HIV-infected adults over a period of 5 months. We assessed renal damage by either proteinuria (≥+ on urine dipstick), reduced creatinine clearance (< 60 ml/min) or reduced estimated glomerular filtration rate (eGFR) of < 60 ml/ min/1.73 m2. The characteristics of cases and controls were compared in analysis and in multivariate logistic regression models with stepwise selection. RESULTS Approximately 50% of the screened 106 patients had a qualifying abnormality. Altogether, we identified 55 cases with 110 age- and gender-matched controls. Mean eGFR was 90.7 (4.8) for cases vs. 106.1 (2.3) ml/min/1.73 m2 for controls (p = 0.001). Cases had a longer duration of HIV infection, more complex regimen, longer exposure to antiretroviral therapy and a more frequent diagnosis of acquired immune-deficiency syndrome (AIDS) and hepatitis C virus (HCV) infection. In the logistic multivariate model, renal damage remained significantly associated with longer known duration of HIV infection (OR 2.88, 95% CI: 1.28 - 6.46, p = 0.01), AIDS defining condition (OR 1.09 95% CI: 1.03 - 1.16, p = 0.002) female gender (OR 2.01, 95% CI: 0.96 - 4.18, p = 0.06), and HCV infection (OR 2.12, 95% CI: 0.99 - 4.52, p = 0.05). CONCLUSIONS Duration, antiretroviral regimen and coincidental HCV impacted the frequency of renal abnormalities in our patients.

Letter to the Editor: Successful Rescue Therapy with Raltegravir (MK-0518) and Etravirine (TMC125) in an HIV-Infected Patient Failing All Four Classes of Antiretroviral Drugs

It is mandatory to find antiretroviral therapies that offer increased efficacy in treatmentexperienced patients with HIV-1 infection, a population whose extensive drug resistance restricts treatment options and has a severe effect on infection management.1 The aim in salvage therapy in patients who were highly treatmentexperienced and in whom multiple regimens had failed was so far limited to the new protease inhibitors (PI) and combination with enfuvirtide.2,3 The new antiretrovirals currently in expanded access programs, such as raltegravir and etravirine, show unprecedented level of virologic efficacy. Raltegravir, formerly MK0518, the first integrase inhibitor under clinical development, showed high potency in multidrug-resistant HIV patients including those resistant to currently available antiretroviral drugs.4 Etravirine, formerly TMC-125, a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) appears to be effective against a variety of HIV viruses that are resistant to efavirenz and nevirapine.5 Few data are available regarding the performance of these drugs combinations in heavily PI-experienced patients, including those for whom tipranavir, darunavir, and enfuvirtide have failed. Hereby, we describe the outcome of salvage therapy based on raltegravir and etravirine in a heavily antiretroviral-experienced patient. A 37-year-old Caucasian male, CDC status C3, had experienced multiple failures to all current classes of antiretroviral agents. Specifically, he had failed eight ritonavir-boosted PI combinations, including tenofovir-lamivudine-enfuvirtide-tipranavir/ritonavir, given in May 2004 with replacement of the latest with darunavir/ritonavir in December 2006. Plasma HIV-RNA levels were measured at baseline and during therapy using a commercial assay, the Versant HIV-1 RNA 3.0 Assay (bDNA; Siemens Medical Solutions Diagnostics, Malvern, PA), with a dynamic range of 50–500,000 HIV-1 RNA copies per milliliter. CD4 cell count was determined by direct immunofluorescence in flow cytometry (Beckman Coulter, Fullerton, CA). Genetic analysis of the pol gene including both HIV-1 reverse transcriptase (codons 4-99) and protease (codons 35-247) regions was performed using the Trugene HIV-1 Genotyping Kit (Siemens Medical Solutions Diagnostics).

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

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.