Apulian infectious diseases network: survey on the prevalence of delta infection among chronic HBV carriers in Apulia.

Background: The current prevalence and clinical burden of Hepatitis Delta Virus (HDV) infection in Apulia are unknown. This study aimed to define the current epidemiological scenario of delta infection and to detect difficulties in the diagnosis and clinical management of HDV patients in Apulia. Methods: From May to September 2022, a fact-finding survey was conducted at eight Infectious Diseases Units of the Apulian region; each Unit was asked to complete a questionnaire on screening and diagnosis of HDV infection and demographic, virological, and clinical characteristics of HDV patients. Results: A total of 1,461 HBsAg-positive subjects were followed up on an outpatient basis. Screening for HDV ranged from 30 to 90% of HBsAg + carriers in a single center. Overall, 952 HBsAg ± subjects (65%) were tested for HDV, and 80/952 (8.4%) were anti-HDV positive. Serum HDV RNA was detected only in 15/80 (19%) anti-HDV-positive subjects, and 12/15 patients (80%) were viremic. Sixty-five anti-HDV-positive subjects (81%) were from Italy; risk factors for HDV acquisition included the presence of HDV infection in the family (29/80 = 36%), drug addiction (12/80 = 15%), and co-infection with HCV or HIV (7/80 = 9%). Liver cirrhosis and hepatocellular carcinoma were diagnosed in 41 (51%) and 4 (5%) patients, respectively. Fifty-seven patients (71%) received nucleos(t)ide analog treatment. Conclusions: The results of this survey show that HDV screening is variable and insufficient, thus real prevalence data on delta infection are lacking in Apulia. Moreover, the HDV RNA test is not available in most laboratories and is not provided by the national health system. These results underline the need for an organizational model to optimize the management of HDV patients throughout the Apulian region.

Simultaneous monitoring of SARS-CoV-2 and bacterial profiles from the air of hospital environments with COVID-19-affected patients.

The SARS-CoV-2 presence and the bacterial community profile in air samples collected at the Intensive Care Unit (ICU) of the Operational Unit of Infectious Diseases of Santa Caterina Novella Hospital in Galatina (Lecce, Italy) have been evaluated in this study. Air samplings were performed in different rooms of the ICU ward with and without COVID-19 patients. No sample was found positive to SARS-CoV-2, according to Allplex 2019-nCoV Assay. The airborne bacterial community profiles determined by the 16S rRNA gene metabarcoding approach up to the species level were characterized by richness and biodiversity indices, Spearman correlation coefficients, and Principal Coordinate Analysis. Pathogenic and non-pathogenic bacterial species, also detected in outdoor air samples, were found in all collected indoor samples. Staphylococcus pettenkoferi, Corynebacterium tuberculostearicum, and others coagulase-negative staphylococci, detected at high relative abundances in all the patients' rooms, were the most abundant pathogenic species. The highest mean relative abundance of S. pettenkoferi and C. tuberculostearicum suggested that they were likely the main pathogens of COVID-19 patients at the ICU ward of this study. The identification of nosocomial pathogens representing potential patients' risks in ICU COVID-19 rooms and the still controversial airborne transmission of the SARS-CoV-2 are the main contributions of this study. Supplementary Information: The online version contains supplementary material available at 10.1007/s10453-022-09754-7.

Compositional Data Analysis of 16S rRNA Gene Sequencing Results from Hospital Airborne Microbiome Samples.

The compositional analysis of 16S rRNA gene sequencing datasets is applied to characterize the bacterial structure of airborne samples collected in different locations of a hospital infection disease department hosting COVID-19 patients, as well as to investigate the relationships among bacterial taxa at the genus and species level. The exploration of the centered log-ratio transformed data by the principal component analysis via the singular value decomposition has shown that the collected samples segregated with an observable separation depending on the monitoring location. More specifically, two main sample clusters were identified with regards to bacterial genera (species), consisting of samples mostly collected in rooms with and without COVID-19 patients, respectively. Human pathogenic genera (species) associated with nosocomial infections were mostly found in samples from areas hosting patients, while non-pathogenic genera (species) mainly isolated from soil were detected in the other samples. Propionibacterium acnes, Staphylococcus pettenkoferi, Corynebacterium tuberculostearicum, and jeikeium were the main pathogenic species detected in COVID-19 patients' rooms. Samples from these locations were on average characterized by smaller richness/evenness and diversity than the other ones, both at the genus and species level. Finally, the ρ metrics revealed that pairwise positive associations occurred either between pathogenic or non-pathogenic taxa.

Factors Enhancing Treatment of Hepatitis C Virus-Infected Italian People Who Use Drugs: The CLEO-GRECAS Experience.

INTRODUCTION: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients. METHODS: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed. RESULTS: A total of 1,786 PWUDs who were followed up were available for assessment. Most PWUDs (85.4%) were managed inside the specialized outpatient addiction clinics (SerDs). The overall SVR rate was 95.4%. The SerDs group achieved an SVR rate of 96.2% compared with 91.6% of the non-SerDs group (P < 0.001). Comparison with the non-SerDs group and the control HCV group showed a significant difference in the dropout rate (0.6% in the SerDs group versus 2.8% in the non-SerDs group and 1.2% in the control group; P < 0.001). At multivariate analysis, factors independently associated with SVR were use of the most recent regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir; odds ratio: 3.126; P = 0.000) and belonging to the SerDs group (odds ratio: 2.356; P = 0.002). DISCUSSION: The performance of DAAs in PWUD is excellent, if 2 conditions are met: (i) that the latest generation drugs are used and (ii) that the patients are managed within the SerDs.

Resistance Associated Mutations in HCV Patients Failing DAA Treatment.

Currently, treatment of chronic hepatitis C is based on a combination of direct-acting antiviral agents (DAAs) which achieve HCV clearance in more than 95% of patients. Despite this high rate of cure, treatment failures can occur in about 3-5% of treated patients. Resistance associated substitutions (RAS) are commonly detected after virological failure, although their role in real-life DAA failures is still debated. This study aimed to evaluate in real-life DAA-failing patients the prevalence of clinically relevant RASs for the different DAA classes and to identify possible predictors. Fifty consecutive HCV-infected patients who experienced a virological failure to a DAA-containing regimen were included in the study. Direct sequencing of HCV regions involved in DAA resistance (NS3, NS5A and NS5B) was performed with Sanger-based homemade protocols. The presence of mutations in the NS3 and NS5A regions was statistically associated with regimens containing protease inhibitors (p<0.0032) and NS5A inhibitors (p<0.0006), respectively. On the contrary, for the NS5B region, the known mutations associated with the NS5B RNA polymerase inhibitors were detected in treated HCV patients, although there was no statistical significance (p>0.5). A significant correlation was found between the presence of RASs and advanced fibrosis/cirrhosis, but not with age, sex and viral load. Our study demonstrates a high frequency of RASs in patients with DAA failure, thus highlighting the usefulness of genotypic tests in this setting. The identification of RASs may guide the choice of the most appropriate drugs for HCV re-treatment.

Real-life glecaprevir/pibrentasvir in a large cohort of patients with hepatitis C virus infection: The MISTRAL study.

BACKGROUND AND AIMS: It is paramount to identify predictors of treatment failure with direct antiviral agents in 'field-practice' patients, including people who inject drugs (PWID). Data on the efficacy of glecaprevir/pibrentasvir (GLE/PIB) in a field-practice scenario are scant. The multicentre MISTRAL study enrolled 1177 patients, including PWID, to assess real-life efficacy and safety of GLE/PIB and to identify the predictive factors for this treatment. METHODS: This was a prospective, longitudinal study. The outcome variable was the rate of sustained virological response (SVR) at week 12. RESULTS: A total of 123 patients (10%) were infected from hepatitis C virus (HCV) 3. METAVIR fibrosis score was F4 in 104 subjects (9%); 118 patients (10%) were PWID. Overall, 1163/1177 (99%) patients achieved SVR. The baseline clinical factors discriminating between treatment success and treatment failure were age at treatment (P = 0.031) and creatinine level (P = 0.034). SVR rates were not influenced by gender, substance abuse, previous treatment, treatment duration, fibrosis or chronic kidney disease stage. Compared with non-substance users, the 118 PWID exhibited a significantly different genotype pattern distribution (χ2  < 0.001). A total of 40/118 (33.9%) of substance users were HCV3 compared to 83/1056 (7.9%) non-substance users. Only 6 patients (0.5%) reported a serious adverse event. CONCLUSIONS: The MISTRAL study provides evidence of GLE/PIB efficacy in a field-practice scenario in a highly epidemic HCV area in southern Italy; it unveiled significant differences in genotype distribution among the most underserved and difficult-to-treat patient subgroups including PWID.

HepaDisk - A new quality of life questionnaire for HCV patients.

BACKGROUND: Since most patients with hepatitis C virus (HCV) infection now receive treatment irrespective of liver disease severity, special attention to patient quality of life (QoL), including psycho-social aspects, is required. No QoL questionnaire is specific for patients with HCV. AIMS: To develop and validate a short Italian questionnaire (HepaDisk) assessing the QoL of patients affected by HCV with intuitive graphic results that is understandable by patients and physicians. METHODS: A questionnaire, drafted by a steering committee, underwent a Delphi survey. A multicenter, observational study was conducted to validate the developed HepaDisk versus other tools (CLDQ-I, SF-36, WPAI:HCV), and to evaluate its correlation with disease severity in Italian patients with HCV. RESULTS: The 10-item questionnaire was validated in 214 patients. HepaDisk showed a high correlation with CLDQ overall score and WPAI:HCV activity impairment (Spearman's rank correlation: 0.651 and 0.595, respectively) and a lower correlation with SF-36. Strong internal consistency (Cronbach coefficient: 0.912), good test-retest reliability (Pearson's correlation coefficient: 0.789; 95% CI, 0.714-0.865), and responsiveness to changes among improved patients were demonstrated. CONCLUSION: HepaDisk is a reliable and user-friendly tool that can monitor disease impact on patient QoL over time, providing a visual representation easily understandable by both patients and physicians.

Optimization of direct anti-viral agent treatment schedule: Focus on HCV genotype 3.

BACKGROUND AND AIM: Direct antiviral agents (DAAs) have led to high sustained virological responses (SVR) in hepatitis C virus (HCV) patients. However, genotype 3 patients respond to treatment in a suboptimal way. This study aims to identify which of the several treatment schedules recommended for genotype 3 would constitute the best option. METHODS: Twenty-four Italian centers were involved in this real-life study of HCV genotype 3 patients treated with DAAs. To expand the number of cases, we conducted a systematic review of the literature on the outcome of genotype 3 patients treated with DAAs. RESULTS: A total of 233 patients with HCV genotype 3 were enrolled. Cirrhotic patients accounted for 83.7%. Overall, the SVR12 rate was achieved by 205 patients (88.0%); the SVR rates were 78.8% after sofosbuvir/ribavirin, 92.5% after sofosbuvir/daclatasvir ± ribavirin, and 100% after sofosbuvir/ledipasvir (seven patients). No difference in rate of SVR was observed in cirrhotic and non-cirrhotic patients (92.2 vs 94.4) using a combination regimen of NS5A and NS5B inhibitors.The systematic review of the literature provided data of 3311 patients: The mean weighted SVR12 rate was 84.4% (CI: 80.4-87.8); the rates varied from 79.0% (CI: 70.9-85.3) with sofosbuvir/ribavirin, to 83.7% (CI: 66.2-93.1) with sofosbuvir/ledispavir, and to 88.2% (CI: 83.3-91.7) with sofosbuvir/daclatasvir. CONCLUSIONS: Our results reinforce the concept that patients with HCV genotype 3 should no longer be considered difficult-to-treat individuals. The optimal therapeutic regimen for these patients appears to be the combination sofosbuvir/daclatasvir, administered for 12 weeks without the use of RBV in non-cirrhotic patients. In cirrhotics the meta-analytic approach suggests extending therapy to 24 weeks.

HCV clearance after direct-acting antivirals in patients with cirrhosis by stages of liver impairment: The ITAL-C network study.

BACKGROUND: Sustained virological response (SVR12) rates at 12 weeks after treatment for HCV-infected patients with decompensated cirrhosis are used when referring to those with moderate functional impairment, while few data are available for those with more severe impairment. The use of the cirrhosis staging system proposed by D'Amico might provide new insights on timing for antiviral therapy. METHODS: We investigated efficacy (SVR12), safety, and post-treatment variations in clinical and laboratory parameters in 2612 patients with advanced fibrosis (n=575) or cirrhosis (n=2037). Cirrhosis was in the compensated phase (without/with varices) or had previously been in the decompensated stage. Different direct-acting antiviral (DAA) regimens were administered in accordance with scientific guidelines. RESULTS: The SVR12 rate was 97.6% in patients with advanced fibrosis. For patients with cirrhosis, the rate was 96.5% in stage 1, 95.1% in stage 2, 100% in stage 3, 95.7% in stage 4, and 93.6% in stage 5. These rates were independent of gender, age, HCV genotype, and treatment schedule. Positive changes in biochemical parameters and CPT classes following therapy were evident in compensated and previously decompensated patients. CONCLUSION: Our findings support the use of DAAs in patients with advanced cirrhosis (stages 3-5) who are at greatest risk and have the most to gain from therapy.

Variation in genes encoding for interferon λ-3 and λ-4 in the prediction of HCV-1 treatment-induced viral clearance.

BACKGROUND & AIMS: In patients with chronic HCV-1 infection, recent evidences indicate that determination of a dinucleotide polymorphism (ss469415590, ΔG/TT) of a new gene, designated IFN λ-4, might be more accurate than the 12979860CC type of the IL28B locus in predicting sustained virological response (SVR) following peg-interferon and ribavirin. In addition, combined genotyping of different SNPs of the IL28B locus was shown to help dissect patients most prone to SVR among those with rs12979860CT. We examined whether single or combined genotyping of two IL28B SNPs, rs12979860 and rs8099917, and ss469415590 variation might improve the prediction of SVR. RESULTS: In the study cohort of 539 patients, 38% had SVR. The SNPs 12979860CC, rs8099917TT, and rs469415590TT/TT correlated significantly with SVR (68%, 50%, and 67%). Carriers of either the triplotype rs12979860CC_ss469415590TT/TT_rs8099917TT or the diplotype rs12979860CC_ss469415590TT/TT had the highest SVR rate (72%). In carriers of the rs12979860 T allele, neither the rs8099917 nor the ss469415590 improved the response prediction. After pooling this finding with data from previous studies, in rs12979860 T heterozygous individuals the co-presence of the rs8099917TT SNP was associated with improved response prediction. CONCLUSION: In HCV-1 patients, the rs12979860 polymorphism appeared as the hit SNP better predicting response following peg-interferon and ribavirin treatment. Additional ss469415590 or rs8099917 genotyping had no added benefit for response prediction. In the subset of carriers of the rs12979860 T allele, genotyping of the rs8099917 SNP was unhelpful in the present investigation, but may inform clinical prediction of treatment response when our data were pooled with previous investigations.

Acute hepatitis C: a 24-week course of pegylated interferon α-2b versus a 12-week course of pegylated interferon α-2b alone or with ribavirin.

UNLABELLED: Therapy of acute hepatitis C (AHC) has not yet been standardized and several issues are still unresolved. This open, randomized, multicenter trial aimed to assess the efficacy and safety of a 24-week course of pegylated IFN (Peg-IFN) alpha-2b versus a 12-week course of Peg-IFN alpha-2b alone or with ribavirin (RBV) in AHC patients. One hundred and thirty HCV acutely infected patients who did not spontaneously resolve by week 12 after onset were consecutively enrolled and randomized to receive Peg-IFN alpha-2b monotherapy (1.5 µg/kg/week) for 24 or 12 weeks (arm 1, n = 44 and arm 2, n = 43, respectively) or in combination with RBV (10.6 mg/kg/day) for 12 weeks (arm 3, n = 43). The primary endpoint was undetectable HCV RNA at 6-month posttreatment follow-up (sustained virological response; SVR). All patients were followed for 48 weeks after therapy cessation. HCV RNA levels were determined by real-time polymerase chain reaction (limit of detection: 15 IU/mL) at the central laboratory at baseline, week 4, end of treatment, and 6 and 12 months posttreatment. Using an intent-to-treat analysis, overall SVR rate was 71.5%. In particular, an SVR was achieved in 31 of 44 (70.5%), 31 of 43 (72.1%), and 31 of 43 (72.1%) patients in arms 1, 2, and 3, respectively (P = 0.898). Sixteen patients (12.3%) prematurely discontinued therapy or were lost to follow-up; thus, sustained response rates with per-protocol analysis were 81.6%, 81.6%, and 81.6% for patients in arms 1, 2, and 3 respectively. With multivariate analysis, virologic response at week 4 of treatment was an independent predictor of SVR. Peg-IFN alpha-2b was well tolerated. CONCLUSION: Peg-IFN alpha-2b induces a high SVR in chronically evolving AHC patients. Response rates were not influenced by combination therapy or treatment duration.

Identification of naïve HCV-1 patients with chronic hepatitis who may benefit from dual therapy with peg-interferon and ribavirin.

BACKGROUND & AIMS: The pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified. METHODS: In 1045 patients treated with peg-interferon and ribavirin, two therapeutic strategies were confronted: the first one evaluated only baseline variables associated with sustained virological response (SVR), and the second one included the rapid virologic response (RVR) in addition to baseline predictors. An 80% SVR rate was the threshold to retain a strategy as clinically relevant. RESULTS: Overall, 414 patients (39.6%) attained SVR. In the first strategy, the hierarchy of features independently associated with SVR was IL28B CC genotype (OR 5.082; CI 3.637-7.101), low (<400,000 IU) viremia (OR 2.907; CI 2.111-4.004), F0-F2 fibrosis (OR 1.631; CI 1.122-2.372) and type 2 diabetes (OR 0.528; CI 0.286-0.972). In the alternative strategy, SVR was associated with RVR (OR 6.273; CI 4.274-9.208), IL28B CC genotype (OR 3.306; CI 2.301-4.751), low viremia (OR 2.175; CI 1.542-3.070), and F0-F2 fibrosis (OR 1.506; CI 1.012-2.242). Combining the favorable baseline variables, the rates of SVR ranged from 42.4% to 83.3%, but only 66 patients (6.3%, overall) with all predictors could be anticipated to reach the >80% SVR threshold. Only 26.6% of no-RVR patients attained SVR. Among the 255 RVR patients, the likelihood of SVR was 61.8% in those with unfavorable predictors, 80% in the presence of a single predictor, and 100% when both predictors were present. By using this model, 200 patients (19.1%) were predicted to have an 80% chance of being cured with dual therapy. CONCLUSIONS: A consistent subset of naïve HCV-1 patients, identified by some baseline characteristics and RVR, may benefit from dual treatment with peg-interferon and ribavirin.

Altered phosphate metabolism in HIV-1-infected patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors that has become a serious problem for HIV-1-infected patients. It has been proposed that disturbance of phosphate metabolism may represent a key feature of MS. Thus, we undertook the present study to investigate the relationship between phosphate levels and the presence of the characteristics of MS. METHODS: One hundred and twenty-one HIV-1-infected patients were consecutively enrolled in a prospective, cross-sectional, single-centre study. Kidney tubular function was examined using tubular resorption of phosphate and normalized renal threshold phosphate concentration. RESULTS: Univariate analysis showed that serum phosphate levels correlated negatively with systolic and diastolic blood pressure, glucose values, waist circumference, insulin, and triglycerides. Moreover, there was a positive relationship between phosphate and high-density lipoprotein (HDL) cholesterol. Multivariate analysis showed that insulin levels were correlated with serum phosphate concentration (r = - 0.24, p = 0.01). CONCLUSIONS: Our data show that HIV-1-infected patients with MS have lower phosphate levels.

Characterization of nontraumatic focal splenic lesions using contrast-enhanced sonography.

PURPOSE: To compare contrast-enhanced sonography (CEUS) with contrast-enhanced CT in the assessment of nontraumatic focal lesions of the spleen. METHODS: CEUS and CT findings in 22 patients with fever of unknown origin and ultrasound-detected splenic focal lesions were analyzed retrospectively. CEUS was performed using an ultrasound unit equipped with a 3.6-MHz probe and contrast-specific software. A 4-ml bolus of second-generation contrast medium was used. The CEUS examinations included a 4-minute recording following injection of the contrast medium. MRI, splenic biopsy, or ultrasound follow-up were used if findings from CT were inconclusive. RESULTS: The final diagnoses were as follows: seven splenic infarcts, five hemangiomas, three lacerations, two benign cysts, one lymphoma, one granuloma, one abscess, and two lesions of unknown etiology. CEUS and CT had the same specificity (77.2%). Both CEUS and CT failed to characterize nodular hypovascular lesions with a hypoenhancing pattern. CONCLUSIONS: CEUS is as effective as CT for characterizing nontraumatic focal lesions of the spleen. If CEUS findings are consistent with a benign splenic lesion, CT seems to be of limited additional value.

Association of visceral adiposity with increased intrarenal artery resistive index in HIV-1-infected patients receiving highly active antiretroviral therapy.

PURPOSE: The aim of our study was to evaluate whether perirenal fat thickness (PRFT), a parameter of central obesity, is related to kidney function and intrarenal artery resistive index (IARI) in human immunodeficiency virus (HIV)-1-infected patients. MATERIALS AND METHODS: We enrolled 102 consecutive HIV-1-infected patients receiving highly active antiretroviral therapy for more than 12 months in a prospective cohort study. Echographically, the PRFT and IARI were measured and the serum metabolic parameters were evaluated. PRFT and IARI were measured using a 3.75 MHz convex linear probe. RESULTS: The mean of PRFT and IARI in HIV-1-infected patients with visceral obesity was considerably higher than that in patients without it (P <0.001 and <0.01, respectively). Using the average IARI as the dependent variable, age (odds ratio, 1.07; 95% confidence interval [CI], 1.01-1.14; P < 0.5) and PRFT (odds ratio, 1.28; 95% CI, 1.08P-1.51; P<0.01) were independent factors associated with IARI. CONCLUSION: Our data indicate that ultrasonographic assessment of PRFT may have a potential to be a marker of increased endothelial damage with specific involvement of the renal vascular district in HIV-1-infected patients.

Severe hepatitis with autoimmune features following a HHV-6: a case report.

HHV-6 has been identified as the aetiologic agent of exanthem subitum in infants and an acute febrile illness in young children. HHV-6 probably remains latent in the body after the primary infection and it reactivates upon host immunosuppression in a manner similar to other human herpes viruses. Primary HHV-6 infection in adults is very rare and it is not clear whether disease manifestations are similar to those observed in children.We report the case of acute hepatitis in a 18-year-old immunocompetent woman presenting with sever jaundice and liver dysfunction. Serum immunoglobulin levels were elevated (3.8 gr/dl) with a titre of anti nucleus antibody of 1:640. Serological data demonstrated the presence of IgM antibodies against human herpesvirus-6 in the serum and of viral DNA on liver biopsy by real time quantitative polymerase chain reaction, with a viral load of 280 genomes/106 of cellular genomes. No other etiologic agents were found to induce hepatitis and the patient was diagnosed as having HHV-6 triggered autoimmune acute hepatitis.

Interruption of highly active antiretroviral therapy in HIV clinical practice: results from the Italian Cohort of Antiretroviral-Naive Patients.

OBJECTIVES: To investigate the frequency of a first therapy interruption (TI) > or = 12 weeks, to identify the factors associated with TI and with therapy resumption, and to compare the risk of developing clinical events during TI and during continuous therapy. METHODS: Observational study of 3142 patients who started a first highly active antiretroviral therapy (HAART) regimen. End points were time to (1) first TI of > or = 12 weeks, (2) subsequent therapy resumption, and (3) development of new AIDS-related events or death. RESULTS: Over a median follow-up period of 41 months (interquartile range: 18-60 months), 721 patients (22.9%) interrupted HAART for > or = 12 weeks, with a probability of 28.6% (95% confidence interval [CI]: 26.7-30.6) by 4 years from the date of therapy initiation. Patient decision (47.4%) and toxicity (24.0%) were the main reasons for TI. Women, injection drug users, and patients with a higher current CD4 cell count were more likely to interrupt. The median time to therapy resumption was 12 months (95% CI: 11-14). The higher the current CD4 count, the slower was the rate of resuming therapy; conversely, patients who stopped because of failure and those with a pre-HAART viral load >100,000 copies/mL resumed therapy sooner. Two hundred eighty-one patients experienced clinical progression at a rate of 2.6 per 100 person-years (pys) (95% CI: 2.3-3.0) while patients were on therapy and 3.5 per 100 pys (95% CI: 2.4-4.8) during TI. The adjusted relative hazard of clinical progression associated with TI was 2.75 (95% CI: 1.14-6.65; P = 0.03). CONCLUSIONS: TI occurring in clinical practice is associated with an increased risk of clinical progression; hence, it should be discouraged outside strictly experimental settings.

The management of hepatitis B virus/HIV-1 co-infected patients starting their first HAART regimen. Treating two infections for the price of one drug?

We examined the impact of a lamivudine-containing highly active antiretroviral therapy (HAART) regimen on 164 hepatitis B virus/HIV co-infected individuals starting their first HAART. Lamivudine-treated patients (accounting for 73% of the study population) showed a significantly lower level of alanine aminotransferase over follow-up [-81.1 mU/ml mean difference; 95% confidence intervals (95% CI): -30.3; -131.7, P=0.003] and a significantly reduced risk of liver-related morbidity/mortality [Relative hazard (RH)=0.07; 95% CI: 0.01-0.38, P=0.002] than those starting a lamivudine sparing-regimen.

Virologic and immunologic response to regimens containing nevirapine or efavirenz in combination with 2 nucleoside analogues in the Italian Cohort Naive Antiretrovirals (I.Co.N.A.) study.

This nonrandomized study compared the virologic and immunologic responses to potent regimens containing either efavirenz or nevirapine after considering potential systematic differences between patients receiving these drugs. Virologic failure was defined as the first of 2 consecutive measurements of virus load >500 human immunodeficiency virus RNA copies/mL. Of the 694 patients included in the analysis, 460 (66.3%) started nevirapine and 234 (33.7%) started efavirenz. The adjusted relative hazard of virologic failure for patients who started nevirapine, compared with those who started efavirenz, was 2.08 (95% confidence interval, 1.37-3.15; P=.0006). In addition, patients receiving efavirenz tended to recover 5 CD4 cells/microL more per quarter (P=.05). Although comparisons of drug efficacy in nonrandomized studies should be viewed with caution, no results from randomized controlled comparisons of these drugs are thought to be available. The findings of this study are in agreement with those of other observational studies.