HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels.

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.

Different impact of NNRTI and PI-including HAART on bone mineral density loss in HIV-infected patients.

OBJECTIVE: To evaluate the changes in Bone Mineral Density (BMD) and bone remodelling markers in a group of HIV patients treated with HAART and controlled in a long follow-up and to identify possible risk factors for accelerated bone mass loss. PATIENTS AND METHODS: In a series of 172 HIV patients treated with HAART a total of 67 patients (44 males and 33 females) underwent repeated bone mineral density measurement by DEXA in lumbar spine and in femur; the patients were classified according to T-score WHO criteria. Serum bone alkaline phosphatase (BAP), by IRMA, and urine pyridinoline/deoxypyridinoline (PYD&DPD), by EIA, were also assayed in all cases. RESULTS: At baseline, 62/67 patients were on HAART, while 5 were naïve; 44.8% were previous intravenous drug users (IVDU), 46.3% heterosexual and 8.9% homosexual, mean age being 40.2 ± 6.5 years, and 23.9% had previous AIDS diagnosis. Fifteen/67 (22.4%) of treated patients had osteoporosis and 25/67 (37.3%) osteopenia in spine and/or femur including 3 naïve, 27/67 (40.3%), including 2 naïve, had normal BMD in both sites. Fifty-one/67 patients were monitored during follow-up (56.8 ± 5.3 months); 27 (52.9%) of these (Group 1), received protease inhibitors (PI) and 24 (47.1%), including naïve, (Group 2) received not nucleoside reverse transcriptase inhibitors (NNRTI) for > 50% of follow-up period. In Group 1 patients, BMD reduction was observed after follow-up in respect of basal condition in both spine and femur, but significantly (p = 0.011) only for the latter. However, mean BMD values remained stable in both sites in Group 2 patients. Basal BAP and PYD&DPD levels were higher in Group 1 than Group 2, but not significantly. Moreover, only PYD&DPD levels at the follow-up evaluation were significantly (p = 0.031) higher in Group 1 than Group 2. Of the remaining 16/67 patients with osteoporosis/osteopenia, 10 received PI and 6 NNRTI and were treated with therapies that could increase bone density, in particular, 9 with Alendronate/Vitamin D/Calcium and 7 with only vitamin D/calcium; these patients were excluded from statistical analysis of 51 Group 1/Group 2 cases. In the 16 patients, after these specific treatments, mean spine and femur BMD increased over time, but significantly only in those cases including alendronate in their protocol. CONCLUSIONS: The study showed that in HIV patients on HAART BMD decrease, even osteoporosis, can be present persisting over time, particularly in PI in respect of NNRTI treated patients. The pathogenesis is probably multifactorial, the different antiviral drugs seeming to differently affect bone metabolism. Alendronate/Vitamin D/Calcium therapy can be useful to slow down bone mass loss and also improve osteoporosis/osteopenia conditions, thus, reducing fracture risk also continuing HAART.

HPV infection in HIV-positive females: the need for cervical cancer screening including HPV-DNA detection despite successful HAART.

PURPOSE: To identify the presence of Human Papilloma Virus (HPV) infection and evaluate the role of Highly Active Antiretroviral Treatment (HAART) in patients with HIV-HPV co-infection. We also compared cytological screening results with HPV-DNA detection to implement screening programs and prevention of invasive cervical cancer (ICC) in HIV-infected females. PATIENTS AND METHODS: We enrolled HIV-infected females presenting for routine clinical evaluation. HPV-DNA of high/intermediate and low-risk types was detected from cervical specimens by nucleic acid hybridization assay with signal-amplification. Patients were divided into two groups according to the presence of HPV co-infection (HPV+) or not (HPV-). RESULTS: We enrolled 57 HIV-infected females. Median age was 40 (IQR 35-44) years, mean CD4 count was 547 ± 227 cells/mm(3), 45 (78.9%) had undetectable HIV-RNA and 52 (91.2%) received HAART. Globally, 19/57 (33.3%) patients were HPV-infected, 16/57 (28.1%) with high/intermediate and 3/57 (5.3%) with low-risk types. Five of the 19 (26.3%) HPV+ patients carried both types. Correlating high-risk genotype HPV-DNA detection with cytology, 17.5% of women with negative cytology, 36.4% with ASCUS (Atypical Squamous Cells of Uncertain Significance) and 83.4% of women with positive cytology (50% of LSIL: low-grade squamous intraepithelial lesion and 100% of HSIL: high grade SIL) were HPV positive. No statistical difference when comparing HPV+ and HPV-patients in age, CD4 cell count, in the proportion of previous intravenous-drug use, previous AIDS and of those receiving HAART with undetectable HIV-RNA was observed. CONCLUSIONS: Cervical cancer screening including HPV-DNA detection should be implemented in HIV infected females across Europe, also when receiving successful HAART, to early identify the HIV patients at risk for ICC to be submitted to more frequent follow up and proper treatment.

Proteomic characterization of hepatitis C eradication: enzyme switch in the healing liver.

Lipid pathway impairment, decrease in the antioxidant pool and downregulation in amino-acid metabolism are just some of the metabolic variations attributed to chronic HCV infection. All of them have been studied separately, mainly in animal models. Thanks to proteomic analysis we managed to describe (for the fist time to the best of our knowledge), in vivo and in humans, the metabolic alterations caused by HCV, and the recovery of the same alterations during HCV treatment. We performed proteomic analysis on liver specimens of a 28-year-old woman affected by hepatitis C genotype 1a, alcoholism and diabetes mellitus type 1, before and after antiviral treatment with pegylated interferon alpha 2b and ribavirin. The subject, thanks to a patient-tailored therapy, reached Sustained Virological Response. Throughout the treatment period the patient was monitored with subsequent biochemical, clinical and psychological examinations. The data obtained by the patient's close monitoring suggest a direct interaction between insulin resistance and an active HCV genotype 1 infection, with a leading role played by the infection, and not by insulin resistance, as demonstrated by the sharp fall of the insulin units needed per day during treatment. The proteomic analysis showed that after therapy, a downregulation of enzymes involved in amino acid metabolism, glycolysis/gluconeogenesis and alcohol catabolism takes place, the latter probably due to cessation of alcohol abuse. On the contrary, the metabolic pathways linked to metabolism of the reactive oxygen species were upregulated after therapy. Finally, a significant alteration in the pathway regulated by peroxisome proliferator-activated receptor alpha (PPARA), a major regulator of lipid metabolism in the liver, was reported. These "real time" data confirm in vivo, in humans, that during HCV infection, the pathways related to fatty acids, glucose metabolism and free radical scavenging are inhibited. The same enzyme deficit is completely recovered after HCV eradication.

Chronic obstructive pulmonary disease: an emerging comorbidity in HIV-infected patients in the HAART era?

PURPOSE: The objective of our study was to evaluate the presence of respiratory symptoms and chronic obstructive pulmonary disease (COPD) in a human immunodeficiency virus (HIV)-infected outpatient population and to further investigate the role of highly active antiretroviral therapy (HAART) and other possibly associated risk factors. METHODS: We consecutively enrolled in a cross-sectional study HIV-infected patients and HIV-negative age, sex and smoking status matched controls. All participants completed a questionnaire for pulmonary symptoms and underwent a complete spirometry. RESULTS: We enrolled 111 HIV-infected patients and 65 HIV-negative age- and sex-matched controls. HIV-infected patients had a significantly higher prevalence of any respiratory symptom (p = 0.002), cough (p = 0.006) and dyspnoea (p = 0.02). HIV-infected patients also had a significantly higher prevalence of COPD in respect of HIV-negative controls (p = 0.008). Furthermore, HIV-infected individuals had significantly (p = 0.002) lower forced expiratory volume at one second (FEV1) and FEV1/forced vital capacity (FVC) ratio (Tiffeneau index) (p = 0.028), whereas the total lung capacity (TLC) was significantly higher (p = 0.018). In the multivariate analysis, significant predictors of respiratory symptoms were current smoking [adjusted odds ratio (AOR) 11.18; 95 % confidence interval (CI) 3.89-32.12] and previous bacterial pneumonia (AOR 4.41; 95 % CI 1.13-17.13), whereas the only significant predictor of COPD was current smoking (AOR 5.94; 95 % CI 1.77-19.96). HAART receipt was not associated with respiratory symptoms nor with COPD. CONCLUSIONS: We evidenced a high prevalence of respiratory symptoms and COPD among HIV-infected patients. HIV infection, current cigarette smoking and previous bacterial pneumonia seem to play a significant role in the development of respiratory symptoms and COPD. Thus, our results suggest that the most at-risk HIV-infected patients should be screened for COPD to early identify those who may need specific treatment.

Hepatitis E virus and hepatitis A virus exposures in an apparently healthy high-risk population in Italy.

PURPOSE: The prevalence of anti-hepatitis E virus (HEV) and anti-hepatitis A virus (HAV), as well as the possible links with socio-demographic and other viral risks factors, were evaluated in an inmates population. METHODS: The study population consisted of 973 consecutively recruited inmates of eight Italian prisons. RESULTS: The anti-HEV prevalence was 11.6 % (113/973). It increased significantly by age (χ(2) for linear trend: p = 0.001) and was significantly higher among non-Italian compared to Italian inmates (15.3 vs. 10.7 %, respectively). Age >40 years [odds ratio (OR) 2.1; 95 % confidence interval (CI) 1.4-3.1], non-Italian citizenship (OR 1.8; 95 % CI 1.1-2.9) and anti-HIV seropositivity (OR 2.2; 95 % CI 1.2-4.2) were the only factors independently associated to anti-HEV positivity by logistic regression analysis. The overall anti-HAV prevalence was 86.4 %, and was significantly higher in non-Italian compared to Italian prisoners (92.6 vs. 84.9 %, respectively; p = 0.02). Age older than 40 years (OR 3.6; 95 % CI 2.2-5.9), <5 years formal education (OR 2.1; 95 % CI 1.3-3.2) and non-Italian nationality (OR 2.7; 95 % CI 1.5-4.8) were factors independently associated to anti-HAV positivity by the logistic regression analysis. CONCLUSIONS: Compared to the general population, significantly higher anti-HEV and anti-HAV prevalences were observed in an inmates population in Italy. Old age and non-Italian nationality were factors independently related to both HEV and HAV exposures. This data suggest the important role of low socio-economic factors in the transmission of both infections in high-risk populations. The possible epidemiological and/or pathogenetic links between HEV and HIV exposures need to be studied further.

Acute respiratory distress syndrome due to influenza virus A/H1N1v in a patient with HIV/HCV co-infection.

The clinical severity of human infection with the novel influenza virus A/H1N1v has not been completely defined, especially in HIV/hepatitis C virus (HCV) infected patients. Although most patients develop mild to moderate symptoms, severe disease may occur in a limited proportion of cases. We report the case of a 44-year-old man infected with HIV and HCV with a high CD4 cell count who developed acute respiratory distress syndrome associated with influenza virus A/H1N1v infection. The patient recovered completely after oseltamivir therapy and mechanical ventilation.

Interferon-γ release assay in people infected with immunodeficiency virus.

The present study aimed to use QuantiFERON TB Gold in tube (Cellestis Limited, Carnegie, Victoria, Australia) as a tool for the screening for tubercular infection in HIV-positive patients. Seventy-three HIV-positive subjects were tested. For each individual, QuantiFERON TB in tube was performed. The immunoassay was negative in 53 subjects, positive in eight and indeterminate in 12. The data obtained indicate that factors such as the CD4 cell count and their percentage, as well as the stage of the disease, could affect the performance of the interferon-γ release assay in populations at risk such as HIV-positive subjects.

Serum leptin and bone metabolism in HIV patients treated with highly active antiretroviral therapy.

AIM: The role of leptin in bone metabolism has not yet been fully elucidated and results remain controversial. We investigated whether changes in serum leptin correlated to bone mineral density (BMD) occur in human immunodeficiency virus (HIV) patients on highly active antiretroviral therapy (HAART). METHODS: The study population was 117 HIV patients (67 men, 50 women) on HAART and 50 healthy controls, all with normal body mass index (BMI). Based on whole body BMD as measured by dual energy x-ray absorptiometry (DEXA), patients were classified as having a low (< -1) T-score (L) or a normal (> -1) T-score (N); DEXA scans were also used to determine total body fat (TFM) and percent fat (F%); radioimmunologic assays were used to measure leptin, osteocalcin (OC), bone alkaline phosphatase (BAP), 1,25 (OH)2 D in serum, and pyridinium cross-links (PYD & DPD) in urine. RESULTS: Of the 117 HIV patients, 54 (46.1%) were classified as L and 63 (53.9%) as N; BMD in both sexes was lower (P <0.01) among the L patients than among either the N patients or the controls; 25/32 L men and 19/22 women were osteopenic, the remaining were osteoporotic. The mean TFM, F%, OC, BAP and PYD & DPD values were higher and the mean 1,25 (OH)2 D values were lower in the L than in the N patients; leptin was higher among the L men (P <0.002) and the L women (P <0.03) than in the N patients. In both sexes. leptin positively correlated with TFM, F%, BAP and PYD & DPD; however, leptin, TFM and F% correlated negatively with BMD. A negative correlation was found between 1,25 (OH)2 D and PYD & DPD in women. At follow-up assessment of 56 HIV patients continuing HAART, leptin and BAP increased and 1,25 (OH)2 D decreased, but not significantly; BMD significantly decreased in women and PYD & DPD increased in men (P <0.02). CONCLUSIONS: An inverse relationship was found between leptin and BMD in HIV patients with osteopenia/osteoporosis treated with HAART. While the role of leptin in bone metabolism in a setting of HIV is still unclear, an inhibitory effect of leptin associated with a negative action by HAART may be hypothesized.

Profile of patients triply infected with HIV and the hepatitis B and C viruses in the HAART era.

HIV-HCV-HBV-coinfected patients were assessed to characterize the viral interactions in the setting of HIV coinfection and in the HAART era. All positive anti-HCV antibody and HBs antigen-positive HIV-infected patients were identified at five HIV clinics. Antihepatitis delta (HDV) antibody, serum HIV RNA, HCV RNA, and HBV DNA quantification and genotype determinations were performed. Out of 67 patients identified 47 (70%) were receiving anti-HBV therapy. HCV RNA and HBV DNA were detectable in 52.5% and 37% of patients, respectively. All possible patterns were found, regardless of anti-HBV therapy. HDV coinfection was associated with undetectable HCV RNA [RR 9.52 (95% CI 1.85-49.01); p = 0.007]. Independent factors predicting undetectable HBV DNA lacked HBeAg [RR 13.94 (95% CI 3.05-63.72); p = 0.001] and use of anti-HBV therapy [RR 11.42 (95% CI 2.43-53.54); p = 0.002]. Replication and genotypes of HCV or HBV had no impact on the replication of the other virus. In conclusion, in this cohort of triple infection (HBV/HCV/HIV) various viral patterns were identified. Spontaneous HCV clearance was frequent, and it was independently associated with HDV coinfection. In the absence of HBV therapy, HBV most often actively replicates. HBV/HCV replication or genotypes were not related to the replication of the other virus.

Bacterial community acquired pneumonia in HIV-infected inpatients in the highly active antiretroviral therapy era.

INTRODUCTION: Highly active antiretroviral therapy (HAART) has deeply modified HIV/AIDS related morbidity and mortality. However, bacterial community acquired pneumonia (BCAP) still represents one of the most frequent causes of morbidity in HIV-infected patients with an inpatient 10% mortality rate. OBJECTIVES: We retrospectively studied the characteristics of BCAP in consecutive HIV-infected inpatients hospitalized from 1999 to 2004 and evaluated the presence of risk factors and the influence of combination antiretroviral therapy receipt on BCAP outcomes. RESULTS: We studied 84 BCAP episodes in 76 HIV-infected inpatients (63 males and 13 females) aged 27-80 years. Thirty-two (42.1%) patients were receiving combination antiretroviral treatment (CART) while 44 (57.9%) were not treated (NART). BCAP incidence progressively increased from 1999 to 2004. The overall percentage of injection drug users was >84%, of smokers >88% and alcohol abusers >32% with no statistical difference between CART and NART. Streptococcus pneumoniae was the most frequently identified pathogen (60%). Time to clinical stability was significantly longer in NART in respect of CART (p=0.011). In multivariate analysis, CDC stage C, CD4 cell count <100 x 10(6) cells/l, and S. pneumoniae etiology were predictors for time to clinical stability >7 days, while receipt of antiretroviral therapy was protective. The percentage of deaths did not differ between CART and NART; most patients had a CD4 count <200 x 10(6) cells/l or severe concomitant diseases. CONCLUSIONS: The incidence of BCAP was high in HIV-infected inpatients observed in the present study mainly due to HIV infection itself, IVDU, alcohol abuse and smoking habit. A longer time to clinical stability was associated with advanced HIV infection and with S. pneumoniae etiology, while receipt of antiretroviral therapy was protective. Injection drug abuse treatment, alcohol abuse and smoking cessation programs, antiretroviral treatment adherence support and pneumococcal vaccination should be implemented to reduce the incidence and to improve the outcomes of BCAP in HIV-infected patients.

Incidence of neutropenia and infections during combination treatment of chronic hepatitis C with pegylated interferon alfa-2a or alfa-2b plus ribavirin.

BACKGROUND: Combination therapy with pegylated interferon (peginterferon) plus ribavirin is associated with several side effects, including neutropenia and infection. AIMS: To evaluate the incidence of neutropenia and infection between all consecutive patients with hepatitis C who were treated in two centers with peginterferon-alfa-2a and peginterferon-alfa-2b, in combination with ribavirin and actively monitored for occurrence of any infection. METHODS: A total of 319 consecutive patients with chronic hepatitis C received once-weekly peginterferon alfa-2b at a weight-adjusted dose (n=162) or peginterferon alfa-2a at a flat dose (n=157), plus ribavirin. RESULTS: Neutropenia was observed in 53 patients overall (17%). There were 73 infections in 73 subjects (23% of the treated population); 4/73 required hospitalization. Infections included respiratory infections (n=23), cellulitis (n=17), dental abscesses (n=13), gastroenteric infections (n=2), and other types of infections (n=18). The incidence of all infections was significantly associated with age, especially over 60 years (p<0.01) but not with neutropenia or type of pegylated interferon. CONCLUSIONS: During the treatment with pegylated interferons and ribavirin, we did not find a correlation between neutropenia and infections. This result provides a support for the notion that current guidelines for pegylated interferons dose reduction in the treatment of chronic hepatitis C for hematologic toxicity could be overly strict.

The changing face of the HIV epidemic in Northern Sardinia: increased diagnoses among pregnant women.

BACKGROUND: Combination antiretroviral therapy has reduced both HIV/AIDS related morbidity and mortality. However, while the number of new AIDS diagnosis progressively declined in Europe from 1997 to 2004, new HIV infection diagnoses showed an increase since 1998. Unfortunately, there is no national HIV reporting system in Italy, and no information is available from the South and the islands. METHODS: Data on new HIV infections diagnosed in northern Sardinia between 1997 and 2004 were retrospectively collected. Thus, two four years periods (1997-2000 vs 2001-2004) were compared in order to assess changes in the characteristics of newly diagnosed individuals. RESULTS: Overall, 156 new HIV infection diagnoses occurred during the study period, 87 (55.8%) in males and 69 (44.2%) in females. The incidence rate per 100,000 inhabitants showed a progressive decline from 1997 (5.9) to 2001 (3.3), followed by a rapid increase in 2002 (5.0) and a new decline in 2004 (3.5). Median age progressively increased over the study period, from 33 years in 1997 to 38 in 2004. Males (55.8%) were more frequently affected than females (44.2%), who showed a trend toward a slight but progressive proportional increase. With regard to the exposure category, 95 (60.9%) individuals were heterosexual contacts, 38 (24.4%) injection drug users (IDU), 17 (10.9%) homosexual men, and 6 (3.8%) not determined (ND). There was a proportional increase for homosexual men (+7.5%) and heterosexual contacts (-7.9%), while IDU showed a slight decrease ( 2.7%). Heterosexual intercourse was the main exposure category both for women (78%) and men (47.1%), but man-to-man sex increased in the last study period. IDU still accounted for 20.3% and 27.5% of the cases among women and men, respectively. An increase in the proportion of new diagnoses in pregnant women, from 8.6% to 20.6%, was also observed. All pregnant women diagnosed in the first four years period were Italian, whereas 4 of the 7 (57.1%) women diagnosed thereafter were foreigner. Finally, the proportion of new HIV diagnoses in foreigners showed a marked increase, from 2.4% to 17.6%; of them 71.4% originated from sub-Saharan Africa. CONCLUSIONS: Our results suggest that the HIV epidemic is far from being controlled in our Region. Prevention campaigns targeted to homosexual men, women and migrants are needed. Non-HIV specialists, such as gynaecologists and obstetricians, as well as general practitioners, should routinely offer HIV testing to pregnant women.

Two cases of human granulocytic ehrlichiosis in Sardinia, Italy confirmed by PCR.

In this work we report the first two cases of human granulocytic ehrlichiosis (HGE) in Sardinia. In early September 2004, a 69-year-old woman (patient 1) was admitted to the Infectious Diseases Institute of Sassari for rickettsiosis like-syndrome: high fever (39.5-40 degrees C), dyspnea, reduced consciousness, vomiting, and cutaneous rash. In late September 2004, a 30-year-old man (patient 2) with high fever was admitted for an evident palmar and oral erythema, edema of the labium, very intense arthralgia, myalgia, and dyspnea. In these two hospitalized patients, the diagnosis was made through indirect IgM and IgG immunofluorescent technique and confirmed by the presence of the specific DNA in the leukocytes. The two patients were A. phagocytophilum-PCR positive.

Correlates of HIV, HBV, and HCV infections in a prison inmate population: results from a multicentre study in Italy.

A cross-sectional study was undertaken on the correlates of infection for the human immunodeficiency virus (HIV) and hepatitis viruses B and C (HBV and HCV) in a sample of inmates from eight Italian prisons. A total of 973 inmates were enrolled [87.0% males, median age of 36 years, 30.4% intravenous drug users (IDUs), 0.6% men who have sex with men (MSWM)]. In this sample, high seroprevalence rates were found (HIV: 7.5%; HCV: 38.0%; anti-HBc: 52.7%; HBsAg: 6.7%). HIV and HCV seropositivity were associated strongly with intravenous drug use (OR: 5.9 for HIV; 10.5 for HCV); after excluding IDUs and male homosexuals, the HIV prevalence remained nonetheless relatively high (2.6%). HIV prevalence was higher for persons from Northern Italy and Sardinia. The age effect was U-shaped for HIV and HCV infections; HBV prevalence increased with age. Tattoos were associated with HCV positivity (OR: 2.9). The number of imprisonments was associated with HIV infection, whereas the duration of imprisonment was only associated with anti-HBc. The probability of being HIV-seropositive was higher for HCV-seropositive individuals, especially if IDUs. In conclusion, a high prevalence of HIV, HCV, and HBV infections among inmates was observed: these high rates are in part attributable to the high proportion of IDUs. Frequency of imprisonment and tattoos were associated, respectively, with HIV and HCV positivity. Although it is possible that the study population is not representative of Italy's prison inmate population, the results stress the need to improve infection control measures users was prisons.

Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis.

PURPOSE: To evaluate the effects of alendronate, vitamin D, and calcium supplementation on bone metabolism and bone mineral density (BMD) in both HIV-infected men and women treated with highly active antiretroviral therapy (HAART). METHOD: We performed a 52-week prospective, multicenter, randomized, open-label clinical trial. Eligible participants were on stable HAART and had BMD values at the femoral neck or lumbar spine that corresponded to a t score less than -1. Patients were randomized to receive alendronate 70 mg weekly or no alendronate; calcium 1000 mg daily and vitamin D 500 IU daily were provided to all study recipients. Primary endpoint of the study was the change in bone metabolism evaluated by N-telopeptide of type 1 collagen and bone-specific alkaline phosphatase; the secondary endpoint was BMD variation. RESULTS: 18 patients were randomized to the alendronate and 23 to the no-alendronate group (controls). The alendronate-treatment group compared to controls had a significant decrease in serum N-telopeptides, 1914 +/- 1433.4 vs. 3967 +/- 1650.5 pM/L (p = .005) after 1 year. Lumbar spine BMD increased by 4% in the alendronate group (p = .004) vs. 3.7% (p = .062) in controls, compared to baseline values. Femoral neck BMD decreased by 0.5% in the alendronate group (p = .05) and by 3.5% in the control group (p = .04). No between-groups differences for BMD were found (Delta lumbar-BMD 0.0351 +/- 0.0406 in cases and 0.0356 +/- 0.073 in controls [p = .977], Delta femoral-BMD -0.085 +/- 0.160 in cases and -0.100 +/- 0.165 in controls [p = .795]). CONCLUSION: Alendronate plus vitamin D and calcium was effective in reducing bone resorption. Alendronate improved lumbar BMD and minimized femoral BMD decrease after 52 weeks compared to treatment with vitamin D and calcium alone in patients on HAART with osteopenia/osteoporosis.

Bone mass loss and vitamin D metabolism impairment in HIV patients receiving highly active antiretroviral therapy.

AIM: Given the few controversial data about the effect of highly active antiretroviral therapy (HAART) on bone mass in HIV patients, we investigated whether a relationship between osteopenia/osteoporosis risk and HAART exists. METHODS: In 172 HIV patients, 152 on HAART, 92 including and 60 not including protease inhibitors (PI), 20 naïve and 64 controls, we measured spine/femur bone mineral density (BMD) by DEXA, and assayed serum osteocalcin (O), bone alkaline phosphatase (BAP), 1,25(OH)2 D, parathormone (PTH), calcium (Ca) and urinary pyridinium cross-links (PYD & DPD). RESULTS: Following WHO BMD t-score criteria, osteopenia was ascertained in >35% of all HAART groups and in 30% of naive. Only HAART patients had osteoporosis, PI patients more frequently, significantly (p<0.03) in spine (21.7% vs 8.3%). Males, intravenous drug users and B-C stage patients have a higher risk for low bone mass. Mean t-score was significantly lower in both spine and femur and O and PYD & DPD higher in PI than non PI patients and controls; 1,25(OH)2 D was significantly lower in all HIV groups than controls, PI patients having the lowest values positively correlating with BMD and negatively with OC and PYD & DPD, and it decreased further in 27 non selected monitored patients continuing on HAART. PTH was higher and Ca lower in HAART patients than controls but not significantly, PTH negatively correlating with BMD. CONCLUSION: HAART could be associated with osteopenia, even osteoporosis, and it could aggravate the loss in bone mass due to HIV infection itself. We hypothesize that HAART may directly affect bone remodelling and/or may indirectly affect vitamin D metabolism.

Usefulness of 99mTc-tetrofosmin scintigraphy in different variants of Kaposi's sarcoma.

We investigated (99m)Tc-tetrofosmin scintigraphy in 27 patients with Kaposi's sarcoma: 20 had classic (CK), 5 AIDS-associated (AK) and 2 transplantation-associated (TK) variants. Twenty-three patients had clinically evident cutaneous and/or mucosal lesions, 9 of them with associated sarcomatous lymphadenopathy; 2 TK patients had only lymph nodes or other extracutaneous Kaposi sites. Both planar and SPECT (99m)Tc-tetrofosmin scintigraphies were performed in all cases and neck pinhole (P)-SPECT in selected patients. (99m)Tc-tetrofosmin uptake was observed in 88% of patients with clinically evident cutaneous and/or extracutaneous Kaposi lesions. Scintigraphy gave additional information on cutaneous lesion extent, particularly SPECT regarding deep invasion and subclinical sites in some cases. However, scintigraphy was less sensitive in the detection of small, isolated and scattered lesions. SPECT/P-SPECT were positive in 8/8 patients with sarcomatous lymph nodes, planar imaging in 5/8, ultrasonography in 7/8, while all procedures were negative in 6 other patients with reactive or HIV infection lymph nodes. SPECT demonstrated lymphadenopathy remission in 1 TK patient after immunosuppressive therapy modification and, like planar imaging, ascertained an associated lymphoma with (67)Ga-citrate combined. (99m)Tc-tetrofosmin scintigraphy, especially SPECT, can be useful both in the detection and staging of Kaposi sarcoma lesions as a complementary tool to clinical and other conventional diagnostic methods.

Identification of HIV patients with active pulmonary tuberculosis using urine based polymerase chain reaction assay.

BACKGROUND: Despite the increased dissemination of tuberculosis among HIV infected patients, the diagnosis is difficult to establish. Traditional microbiological methods lack satisfactory sensitivity. We have developed a highly sensitive and specific nested polymerase chain reaction (PCR) capable of detecting Mycobacterium tuberculosis DNA in urine specimens and have used this test to examine urine specimens from HIV patients with active pulmonary tuberculosis. METHODS: Urine specimens from 13 HIV infected patients with microbiologically proven active pulmonary tuberculosis, 10 AIDS patients with non-tuberculous mycobacterial infection (documented by blood culture), 53 AIDS patients with no evidence of mycobacterial disease, and 80 healthy subjects (25 with positive skin test to purified protein derivative) were tested for M tuberculosis using PCR, acid fast staining (AFS), and culture. RESULTS: Of the urine specimens from patients with active tuberculosis, all tested positive by PCR, two by culture, and none by AFS. No reactivity was observed in urine specimens from patients with non-tuberculous mycobacterial infection. Of the 53 AIDS patients without mycobacterial infection, one had a positive urine PCR. Normal subjects were all negative. CONCLUSIONS: Urine based nested PCR for M tuberculosis may be a useful test for identifying HIV patients with pulmonary tuberculosis.