High HIV prevalence in male patients with acute hepatitis A in the Rome metropolitan area, Italy 2002-2008.

BACKGROUND & AIMS: Several outbreaks of hepatitis A affecting homosexual men have been reported in Europe. However, the prevalence of HIV infection in patients affected by hepatitis A has not been extensively studied and hepatitis A is not considered as an indicator disease for routine HIV testing. METHODS: We retrospectively analyzed all adult cases of acute hepatitis A, reported by the National Institute of Infectious Disease "L. Spallanzani", Rome-Italy, in 2002-2008. Data on HIV infection were obtained by chart review and cross-linkage with laboratory. Information on exposure to risk factors were collected from the standard questionnaire of the Local Health Unit. RESULTS: We analyzed a total of 473 cases of hepatitis A, 368 (77.2%) males that accounted for 75% of all reported cases in Rome, aged 25-64 years (same gender distribution). During the study period, we diagnosed a high proportion of cases among male individuals (78%). Among the male patients, HIV serology was available for 203/368 (55.2%). The overall HIV prevalence was 15.2% (56/368); it was significantly associated with same gender sex and was significantly higher than that observed among patients with hepatitis B (4.0%). CONCLUSIONS: We found a high HIV prevalence, associated with same gender sex, among adult male patients diagnosed with hepatitis A in the period 2002-2008, except for 2006. Our data suggest that in a low incidence area for hepatitis A, with a constant high proportion of cases among male individuals, all individuals with acute hepatitis A should be routinely offered an HIV test.

Neurocognitive impairment and survival in a cohort of HIV-infected patients treated with HAART.

Before the introduction of HAART, HIV-associated neurocognitive impairment (NCI) was recognized as an independent risk factor for death. Since 1996, we conducted a prospective study to assess whether NCI still represents a negative prognostic factor for mortality. Patients were administered measures of neurocognitive function (a battery of 17 neuropsychological tests), clinical and neurological evaluation, laboratory testing, and brain imaging studies. Among the 412 enrolled patients, 224 (54.4%) were neurocognitively impaired and 188 (45.6%) were neurocognitively unimpaired. A durable virological suppression under highly active antiretroviral therapy (HAART) was achieved by 63.3% of unimpaired patients and by 49.6% of impaired patients (p = 0.007). Overall, 47 deaths were recorded, 38 among impaired and 9 among unimpaired patients. At 84 months, the estimated survival proportions in impaired and unimpaired patients were 68.5% and 84.9%, respectively (p < 0.001). At univariate analysis the virological response to HAART was the variable most strongly associated with survival, since patients with virological failure had a nearly 10-fold increased risk of death than those with durable virological suppression (HR = 9.9, 95% CI: 3.9-25.0). After stratification for virological response to HAART, an increased risk of death for neurocognitively impaired patients was seen only among the 182 patients with virological failure (HR: 2.9, 95% CI: 1.2-7.1), while the survival probability of the 230 patients with durable virological suppression was not affected by neurocognitive impairment (p = 0.89). Our results highlight the clinical relevance of HIV-related central nervous system (CNS) involvement in the HAART era, and raise concerns regarding the clinical relevance of CNS involvement as potent antiretroviral therapies become less effective.

Using a database of HIV patients undergoing genotypic resistance test after HAART failure to understand the dynamics of M184V mutation.

OBJECTIVE: M184V/I mutation is associated with high-level phenotypic resistance to lamivudine (3TC). The aim of the present analysis was to correlate the time of appearance/disappearance of M184V/I with duration of 3TC treatment. METHODS: Overall, 211 patients were selected from a database of HIV patients undergoing genotypic resistance test after virological failure of HAART regimens in two major reference centres in Rome between 1999 and 2001. At the time of genotyping, 120 of them (56.9%) were failing a 3TC-including HAART, while 91 (43.1%) received 3TC only in previous HAART. Duration of the current 3TC-containing regimen and the time from the end of last 3TC treatment to genotypic resistance test (GRT) were analysed. RESULTS: Among patients currently undergoing 3TC-containing HAART, the prevalence of M184V/I was 82.5% (78.3/4.2%, respectively) and significantly associated to current 3TC use at GRT. Prevalence of M184V/I was associated to longer history of 3TC (from 47.1% in patients treated with 3TC for <6 months, to 84.0% among those treated for 7-12 months; 100.0% of patients with >42 months of current 3TC carried M184V. At logistic regression analysis, the rate of increase of M184V/I in 3TC-failing patients was statistically significant (OR: 1.066 per month of current 3TC therapy, 95% CI: 1.020-1.114, P<0.01), suggesting a 6.6% monthly increase of probability of M184V/I. Among patients who interrupted 3TC, overall prevalence of M184V/I was 23.1%: proportion of patients carrying the M184V/I dropped from 83.3% among those who interrupted 3TC from < or = 3 months, to 56.3, 20, 10.5 and 0% for those interrupting 3TC from 6, 12, 24 and > or = 24 months, respectively. At logistic regression, the rate of disappearance of M184V/I was also statistically significant (OR: 0.883 per month, 95% CI: 0.804-0.970, P=0.01), indicating a 11.7% monthly decrease of probability of M184V/I after 3TC interruption. CONCLUSIONS: Dynamics of appearance/disappearance of M184V/I mutation is rapid after 3TC failure/interruption, suggesting ease of development of such a mutation, but also suggesting a remarkable growth disadvantage for HIV. From the clinical perspective, recycling of drugs whose antiviral activity is affected by M184V mutation can be successful after appropriate drug wash-out, also in heavily pretreated patients.

Neurocognitive performance and quality of life in patients with HIV infection.

We examined the relationship of HIV-related cognitive impairment and health-related quality of life (QoL). Subjects were administered measures of cognitive function (a battery of 17 neuropsychological tests) and of QoL (the MOS-HIV questionnaire). Study measures also included comprehensive clinical and neurological evaluation, laboratory testing, and brain imaging studies in patients with impaired neuropsychological evaluation. One-hundred and eleven subjects were examined. Cognitively impaired patients (33.3%) reported poorer QoL scores in all domains (p < 0.05): physical health summary score (PHS) (44.6 vs. 49.9), mental health summary score (MHS) (37.7 vs. 44.4), pain (67.6 vs. 79.4), physical functioning (75.9 vs. 87.7), role functioning (32.4 vs. 41.5), social functioning (70.3 vs. 83.5), mental health (48.2 vs. 61.0), energy (53.1 vs. 63.0), health distress (60.8 vs. 75.5), cognitive functioning (CF) (60.5 vs. 71.8), general health perceptions (29.2 vs. 43.4), and QoL (36.5 vs. 47.0). The number of altered neuropsychological tests correlated significantly with MHS (p < 0.001), PHS (p < 0.03), CF (p < 0.02), and QoL (p < 0.02) scores. A correlation between seven of seven neuropsychological measures exploring speed of mental processing, three of four exploring mental flexibility, four of six exploring memory, and two of two exploring fine motor functioning and MHS, PHS, CF, or QoL scores was also found. Poor performance on the Digit Symbol test was most strongly associated with poor MHS (OR 1.04, 95% CI 1.01-1.08, p < 0.009) and PHS (OR 1.04, 95% CI 1.01-1.08, p < 0.01) scores, controlling for CD4 count, previous AIDS diagnosis, receiving HAART, and drug abuse. Cognitive impairment is associated with poor QoL. People with more severe cognitive impairment have the highest probability of having a poor QoL. Cognitive impairment in any cognitive domain explored in our battery is also associated with poor QoL. Poor performance on the Digit Symbol Test is the strongest predictor of poor QoL.

Extra-cerebral severe infections associated with haemorrhagic hereditary telangiectasia (Rendu-Osler-Weber Disease): five cases and a review of the literature.

Hereditary haemorrhagic telangiectasia (HHT) is one of the most common autosomal dominant disorders and is characterized by genetically determined abnormalities of vascular structure. People affected by HHT are predisposed to severe infections such as cerebral abscesses, typical of patients with pulmonary arteriovenous malformations, and extra-cerebral infections such as bacteraemia, septic arthritis, osteomyelitis, hepatic abscesses, skin infections and infective endocarditis. We present a retrospective series of severe bacterial extra-cerebral infections in five patients affected by HHT, admitted to our Institute from January 2007 to June 2013. We also reviewed the literature of the last five years concerning infectious complications in people affected by HHT. Our study shows that HHT patients with infectious complications exclusively localized in extra-cerebral sites are usually fragile, old and affected by comorbidities. Moreover, we recognized a trend of Staphylococcus aureus (SA) severe infection recurrence in such patients, both in our series and in the literature. In our opinion these results suggest the need to evaluate the possible benefits of SA nasal colonization screening and decolonization in such patients.

Molecular characterization of hepatitis A outbreak in the province of Rome, Lazio region, Italy, January-July 2013.

Reduced circulation of hepatitis A virus lead to an increase of susceptible individuals, and outbreaks occurred recently. In Northern Italy an outbreak is ongoing, attributed to a monophyletic genotype IA strain, with mixed frozen berries as probable source. From 01/01/2013 to 07/15/2013, 30 cases were diagnosed at National Institute for Infectious Diseases, Rome, Italy, representing about twice the number of cases in whole 2012. Phylogenetic analysis indicated that most, although not all, infections were attributable to the same monophyletic genotype IA strain identified in the contemporary Northern Italy outbreak. This strain is also very similar to previous isolates from Venezuela.

Salmonella enterica ssp. arizonae infection in a 43-year-old Italian man with hypoglobulinemia: a case report and review of the literature.

INTRODUCTION: Salmonella enterica ssp. arizonae is an uncommon human pathogen with serious infections reported in immunocompromised hosts. In Europe, only a few cases have been described. Patients with this infection usually have a history of contact with reptiles or travel abroad. We present a case report of infection in a patient with hypoglobulinemia and a literature review. CASE PRESENTATION: We describe the case of a 43-year-old Caucasian Italian man with hypoglobulinemia who presented to our hospital with sepsis and diarrhea. A stool culture yielded S. enterica ssp. arizonae. Our patient was treated with oral ciprofloxacin and made a full recovery. We also present a review of the cases of S. enterica ssp. arizonae infections previously reported in Europe. CONCLUSIONS: The majority of infections from S. enterica ssp. arizonae occur in patients who are immunocompromised. Data from the literature suggests that it may be difficult to eradicate the bacteria and thus, prolonged antibiotic courses are often used. It would be advisable for clinicians to investigate for pre-existing immune dysfunction if S. enterica ssp. arizonae is isolated. In Italy, although there have only been a few cases, the likely route of transmission remains unclear and requires further surveillance.

Hemolytic anemia due to acute cytomegalovirus infection in an immunocompetent adult: a case report and review of the literature.

INTRODUCTION: Cytomegalovirus is a common virus responsible for a wide range of clinical manifestations. Hemolysis is a rare but potentially life-threatening complication of cytomegalovirus infection, described mostly in immunocompromised patients, the pathogenesis of which is still unclear.We performed a review of the literature regarding cases of hemolytic anemia during acute cytomegalovirus infection in apparently immunocompetent individuals. We searched for relevant articles in PubMed for the period of 1980 through 2008. CASE PRESENTATION: We describe a case of Coombs-negative hemolytic anemia in a 44-year-old Caucasian immunocompetent man with acute cytomegalovirus infection. CONCLUSION: Clinicians should consider cytomegalovirus infection in the differential diagnosis of hemolytic anemia in immunocompetent adults. Possible therapeutic options include antiviral therapy and steroids, although the best treatment strategy is still controversial.

The effect of age on response to therapy with peginterferon alpha plus ribavirin in a cohort of patients with chronic HCV hepatitis including subjects older than 65 yr.

OBJECTIVES: In many industrialized countries HCV infection is characterized by an increasing prevalence during ageing; however, data on the efficacy of treatment among older patients are scarce. This study was set up to evaluate the effect of age on the treatment of chronic HCV hepatitis with peginterferon alpha plus ribavirin. METHODS: We retrospectively reviewed medical records of 153 adult patients with chronic HCV hepatitis treated with combination therapy; 30 of them (19.6%) were 65 years of age or older. RESULTS: In multivariable analysis, age groups >/=40 years had similar odds of achieving sustained virologic response (P= 0.71) and significantly lower odds of sustained response compared with younger patients (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.05-0.59, P= 0.006; OR 0.13, 95% CI 0.03-0.49, P= 0.002; OR 0.21, 95% CI 0.05-0.91, P= 0.037 for patients aged 40-49 years, 50-64 years, and older than 64 years, respectively). The effect of age was present in the 74 patients infected with genotype 1 or 4 (P= 0.04), while among the 79 patients with genotype 2 or 3 sustained virologic response rates were relatively uniform, with no statistically significant differences. CONCLUSIONS: The probability of good response to combination treatment with peginterferon alpha plus ribavirin is decreased for patients aged more than 40 years infected with genotype 1 or 4, but patients aged more than 65 had a similar rate of response to those aged 40-64 years. Combination treatment may be safely extended to elderly patients with no major contraindications.

Streptococcus salivarius meningitis and sphenoid sinus mucocele. Case report and literature review.

We report a case of meningitis caused by Streptococcus salivarius in a 49-year-old woman with a previously undiagnosed cerebrospinal fluid fistula due to a sphenoid mucocele. We reviewed the literature concerning meningitis caused by this uncommon organism and to the best of our knowledge this is the first case of S. salivarius meningitis associated with sphenoid mucocele.

Prevalence and risk factors for human immunodeficiency virus-associated neurocognitive impairment, 1996 to 2002: results from an urban observational cohort.

To assess prevalence and risk factors for human immunodeficiency virus (HIV)-related neurocognitive impairment (NCI), the authors performed a 7-year survey in the period 1996 to 2002. A total of 432 patients were examined. HIV-related NCI was diagnosed in 238 patients (55.1%), meeting the HIV dementia (HIV-D) criteria in 45 (10.4%). The prevalence of both NCI and HIV-D did not change significantly during the study period. Compared with patients without NCI, patients with NCI were older (40.4 versus 38.2 years; P = .003), had a higher prevalence of positive HCV serology (61.1% versus 38.9%; P = .003), and a lower nadir CD4 cell count (156 versus 222 cells/microl; P < .001). Compared with patients seen during 1996 to 1999, patients with NCI seen during 2000 to 2002 were older (40.7 versus 38.8 years; P = .004), had a less advanced disease stage (previous acquired immunodeficiency syndrome [AIDS] 28.8% versus 65.7%; P < .001) and a higher nadir CD4 count (174 versus 132 cells/microl; P = .026). This study showed an unchanged prevalence of both HIV-related NCI and HIV-D in the period 1996 to 2002. The authors found evidences for new additional potential risk factors for HIV-related NCI (older age, lower nadir CD4 count, positive hepatitis C virus [HCV] serology), and for a change of risk factors for NCI in the late highly active antiretroviral therapy (HAART) era (older age, less advanced disease, higher nadir CD4 count).

Correlates and predictors of adherence to highly active antiretroviral therapy: overview of published literature.

Knowledge of factors associated with medication adherence could help HIV clinicians to target persons in need of intervention, design these interventions, and help researchers to plan studies of adherence. This review summarizes the results of 20 studies investigating the issue of barriers to optimal highly active antiretroviral therapy (HAART) adherence. Only a few determinants were consistently associated with nonadherence. Symptoms and adverse drug effects, psychologic distress, lack of social or family support, complexity of the HAART regimen, low patient self-efficacy, and inconvenience of treatment were the factors most consistently associated with nonadherence. There were inconsistent findings regarding the relationship of adherence and the following variables: sociodemographic characteristics, substance abuse, depressive symptoms, quality of life, CD4+ cell count, knowledge and beliefs about treatment, patients' satisfaction with health care, and patient-provider relationship. A synthesis of findings relating various factors to adherence to HAART is difficult to reach because of several limitations of the existing body of research. These limitations concern the measurement of adherence, the assessment of correlates and predictors of adherence, the study population, and the study design.

Behavioral correlates of adherence to antiretroviral therapy.

The objective of this study was to analyze the relationships between adherence to treatment and sexual and drug-taking behaviors among persons with HIV, who started combination antiretroviral therapy as their first regimen. The authors analyzed data from 366 patients enrolled in a multicenter observational cohort study conducted in infectious disease hospital units in Italy. Adherence measurement was based on responses to a self-administered questionnaire regarding following HIV physician advice on taking medications and missed appointments. Questions on sexual and drug-taking behaviors were also included in the questionnaire. The median time since starting antiretroviral therapy was 11.8 months; 37.4% of patients were on a two-drug regimen and 62.6% were on a three-drug regimen. Overall, 68 patients (18.6%) could be classified as nonadherent. The proportion of patients with viral load < or = 500 copies/mL was significantly higher among adherent patients (68%) compared with nonadherent patients (40.4%; p = .001). In multivariable analysis, age (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.42-0.98, per 10-year increment) and current use of injection (OR, 3.47; 95% CI, 1.40-8.5) or noninjection drugs (OR, 4.23; 95% Cl, 1.85-9.67) were significantly associated with nonadherence. No significant association was found between adherence and sexual behaviors. The data do not support the hypothesis that among HIV-infected person on antiretroviral therapy, poor adherence is associated with high-risk sexual behaviors that may further spread the infection.

Patient-reported and physician-estimated adherence to HAART: social and clinic center-related factors are associated with discordance.

OBJECTIVES: To evaluate the rate of discordance between patients and physicians on adherence to highly active antiretroviral therapy (HAART) and identify factors related to discordance in these two assessments. DESIGN: Prospective, multicenter, cohort study (AdICONA) nested within the Italian Cohort Naive Antiretrovirals (ICONA) study. SETTING: Tertiary clinical centers. PARTICIPANTS: The patients filled out a 16-item self-administered questionnaire on adherence to HAART. At the same time, physicians estimated the current HAART adherence of their patient. MAIN OUTCOME MEASURE: Discordance between patient and physician on adherence to antiretroviral therapy. RESULTS: From May 1999 to March 2000, 320 paired patient-physician assessments were obtained. Patients had a mean plasma HIV RNA of 315 copies/ml (64% had undetectable HIV RNA) and a mean CD4+ cell count of 577 cells x 10(6)/L. Nonadherence was reported by 30.9% of patients and estimated by physicians in 45.0% cases. In 111 cases (34.7%), patients and physicians were discordant on adherence to HAART. Kappa statistics was 0.27. Using patient-assessed adherence as reference, sensitivity, specificity, positive predictive value, and negative predictive value of physician-estimated adherence were 64.7%, 66.6%, 81.2%, and 45.8%, respectively. On multivariable analysis, low education level, unemployment, absence of a social worker in the clinical center, and unavailability of afternoon visits were significantly correlated with patient-physician discordance on adherence to antiretrovirals. CONCLUSIONS: Physicians did not correctly estimate patient-reported adherence to HAART in more than one third of patients. Both social variables and factors related to the clinical center were important predictors of discordance between patients and physicians. Interventions to enhance adherence should include strategies addressed to improve patient-physician relationship.