Point-of-care testing for hepatitis C virus infection at an Italian dental clinic: portrait of the pilot study population.

The dental clinic is an appropriate place to promote the prevention of hepatitis C virus (HCV) infection and fast access for care of HCV-positive subjects with new-generation anti-HCV drugs. This study aimed to determine the socio-demographic profile of subjects screened for HCV virus in a dental clinic to acquire useful information for future campaigns of prevention. An easy, free-of-charge, screen salivary test was offered to patients referred to the dental clinic of San Raffaele Scientific Research Hospital in Milan, Italy for dental procedures. These patients were also asked to complete an anonymous questionnaire on demographics and risk behaviours. A total of 1388 of 2097 (66.19%) questionnaires were evaluable. The demographics of the population responding to this initiative was primarily Italians citizen (96.47%), homogeneous gender distribution (55.55%), age over 50 (609 subjects; 43.88%), with high-level education and stable professional positions. 905 subjects (65.20%) were never tested for HCV before. The test showed positive reactivity in 22 cases (1.05%); of these, 21 subjects were known to be HCV-positive, and the test confirmed their status. One subject was newly diagnosed as HCV-positive. The percentage of subjects who were never tested for HCV infection appears too high (905 subjects, i.e., 65.20%), especially among subjects with high level of education and professions, and among adults over 40 or young people (18-25). The easy screening test in dental clinic can help raise awareness, promote early diagnosis and prevention, and provide a fast link to care for HCV infection.

Point-of-care testing for hepatitis C virus infection at alternative and high-risk sites: an Italian pilot study in a dental clinic.

The Infectious Diseases Department and the Department of Dentistry of San Raffaele Scientific Institute in Milan conducted a screening and prevention program, the "EASY HCV-test Program," at a dental clinic to increase the identification of unrecognized infections. Using a cross-sectional community-based study design, hygienists in the dental clinic offered patients a hepatitis C virus (HCV) rapid salivary test (OraQuick ADVANCE® Rapid HCV Antibody Test) with pre- and post-test counseling prior to initiation of their oral hygiene routine. From April 2015 to November 2015, the EASY HCV test was offered to 2650 patients visiting the Center of Oral Health and Prevention at the Department of Dentistry at San Raffaele Hospital in Milan. Among them, 2077 eligible volunteers were tested. The test showed positive reactivity in 22 cases; of these, 21 subjects were known to suffer from HCV, and the test confirmed their status. One subject was newly diagnosed with HCV infection. The results of this study suggest EASY HCV test screening conducted in dental clinics may constitute an effective strategy for increasing HCV testing among people at risk for infection.

Early diagnosis and retention in care of HIV-infected patients through rapid salivary testing: a test-and-treat fast track pilot study.

Aim of this study was to evaluate the efficacy and the retention-in-care of individuals diagnosed during six years of salivary HIV testing (EASY-test project). Among those linked-to-care at the Infectious Diseases Department of San Raffaele Hospital (Milan, Italy), the proportion of patients engaged, retained in care and virologically suppressed after the antiretroviral treatment was 96%, 100% and 95.2%, respectively. Results from our study suggest that salivary HIV testing may help bring to light cases of HIV infection otherwise undiagnosed, and thus favour a more rapid and wider reduction of the HIV infection burden at the population level.

Cross-sectional study of community serostatus to highlight undiagnosed HIV infections with oral fluid HIV-1/2 rapid test in non-conventional settings.

The submerged portion of undiagnosed HIV infection in Italy is about 30% of subjects found seropositive. This fact represents one of the most important public health problems hindering the control of infection progression. This means we need to fight unawareness and social stigma and promote easy and friendly access to HIV test. We developed a Prevention Program called "EASY test Project", offering a new rapid HIV test on oral fluid, to evaluate the acceptability of an alternative, free and anonymous test available in different settings (on board a "Motor Home" at public events, Points of Care, STDs outpatient prevention units and GP surgeries). From December 2008 to December 2012 we performed 7,865 HIV saliva tests, with 50 new infections found (0.6% of the total) out of 140,000 informed subjects. From the self-reported characteristics of respondents, the population approaching the EAST test project was represented by males (70%) aged between 20 and 50 years, 61% with a medium-high education level, 62% homosexuals (MSM), 88% reported unsafe sexual behaviours, and 48% had never undergone an HIV screening test. In five years of the Prevention Program, 100% of subjects interviewed gave a general favorable consent in approaching rapid and not invasive screening, immediate return of the result, and a timely specialized approach and treatment of HIV positive subjects. Results from our study confirm that the rapid and alternative test may contribute to HIV prevention strategies and to the control of the spread of infection and HIV disease progression by reaching a larger population, particularly when and where regular screening procedures are difficult to obtain or are not preferred.

Offer of rapid testing and alternative biological samples as practical tools to implement HIV screening programs.

Implementation of HIV testing has the objective to increase screening, identify and counsel persons with infection, link them to clinical services and reduce transmission. Rapid tests and/or alternative biological samples (like oral fluid) give the option for a better general consent in approaching screening, immediate referral of HIV positives to medical treatment and partner notification. We tested the performance characteristics of an oral fluid-based rapid HIV test (Rapidtest HIV lateral flow-Healthchem diag. LLC) in comparison with routinely utilized methods in a selected population of known positive (N = 121) or negative (N = 754) subjects. The sensitivity of the rapid test was 99.1% (one false negative sample) and the specificity 98.8%. Five negatives showed a faint reactivity, 3 of these were reactive also in the reference test, one with a p24 only reaction in Western blot. If these 3 samples were excluded from the analysis the specificity increases to 99.2%. Results from our study confirm that, although a continuous improvement of the test performance is still needed to minimize false negative and positive results, rapid test and alternative biological samples may contribute to HIV prevention strategies by reaching a larger population particularly when and where regular screening procedures are difficult to obtain.

Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients.

BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent and is associated with substantial morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). We compared the efficacy and safety of pegylated interferon alfa-2a (peginterferon alfa-2a) plus either ribavirin or placebo with those of interferon alfa-2a plus ribavirin for the treatment of chronic HCV infection in patients who were also infected with HIV. METHODS: A total of 868 persons who were infected with both HIV and HCV and who had not previously been treated with interferon or ribavirin were randomly assigned to receive one of three regimens: peginterferon alfa-2a (180 microg per week) plus ribavirin (800 mg per day), peginterferon alfa-2a plus placebo, or interferon alfa-2a (3 million IU three times a week) plus ribavirin. Patients were treated for 48 weeks and followed for an additional 24 weeks. The primary end point was a sustained virologic response (defined as a serum HCV RNA level below 50 IU per milliliter at the end of follow-up, at week 72). RESULTS: The overall rate of sustained virologic response was significantly higher among the recipients of peginterferon alfa-2a plus ribavirin than among those assigned to interferon alfa-2a plus ribavirin (40 percent vs. 12 percent, P<0.001), or peginterferon alfa-2a plus placebo (40 percent vs. 20 percent, P<0.001). Among patients infected with HCV genotype 1, the rates of sustained virologic response were 29 percent with peginterferon alfa-2a plus ribavirin, 14 percent with peginterferon alfa-2a plus placebo, and 7 percent with interferon alfa-2a plus ribavirin. The corresponding rates among patients infected with HCV genotype 2 or 3 were 62 percent, 36 percent, and 20 percent. Neutropenia and thrombocytopenia were more common among patients treated with regimens that contained peginterferon alfa-2a, and anemia was more common among patients treated with regimens containing ribavirin. CONCLUSIONS: Among patients infected with both HIV and HCV, the combination of peginterferon alfa-2a plus ribavirin was significantly more effective than either interferon alfa-2a plus ribavirin or peginterferon alfa-2a monotherapy.

Rate of cirrhosis progression reduced in HIV/HCV co-infected non-responders to anti-HCV therapy.

This is a retrospective longitudinal follow-up study of 25 HIV/HCV positive cirrhotic patients not responding to peg-IFN plus ribavirin, and 25 untreated controls matched for age (+/-5 years), gender and Child-Pugh score. The primary endpoint of the study was the incidence of cirrhosis progression (CP) defined as the occurrence of at least one of the following events: death, ascites, jaundice, encephalopathy, gastrointestinal bleeding and hepatocellular carcinoma (HCC). During the median follow-up of 54 months (34-89), four treated (16%) and 13 untreated patients (52%) experienced CP (p = 0.02). Poisson's regression model showed that the independent predictors of CP were Peg-IFN therapy (p = 0.016), positive HIV-RNA (p = 0.024), and altered ALP values (p = 0.012). Peg-IFN therapy seems to slow down the rate of cirrhosis progression also in HIV/HCV co-infected patients nonresponders to anti-HCV therapy, in comparison with untreated patients.

Efficacy and safety of daclatasvir plus pegylated-interferon alfa 2a and ribavirin in previously untreated HCV subjects coinfected with HIV and HCV genotype-1: a Phase III, open-label study.

BACKGROUND: Daclatasvir (DCV) is a potent, pangenotypic, hepatitis C virus (HCV) non-structural protein 5A inhibitor with low potential for drug interactions with antiretroviral therapy (ART). We evaluated the safety and efficacy of DCV plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in HIV-1/HCV genotype-1-coinfected patients. METHODS: AI444043 (NCT01471574), an open-label, Phase III, single-arm, response-guided treatment (RGT) study included 301 patients. They received DCV doses of 30, 60 or 90 mg once daily (depending on concomitant ART), plus weight-based RBV (<75 kg, 1000 mg/day; or ≥75 kg, 1200 mg/day), and once-weekly PegIFN 180 µg, for 24 weeks. If required by RGT, PegIFN/RBV without DCV was extended for an additional 24 weeks of therapy. The primary endpoint was the proportion of patients with sustained virologic response at post-treatment Week 12 (SVR12). RESULTS: Overall, 224 (74%) patients achieved SVR12 and the lower bound of the 95% confidence interval was higher than the historic SVR rate with PegIFN/RBV alone (70 vs. 29%). Most common adverse events (AEs) were fatigue, neutropenia, anemia, asthenia and headache. On-treatment serious AEs occurred in 24/301 (8%) patients; 18/301 (6%) discontinued treatment due to AE. CONCLUSIONS: DCV + PegIFN/RBV led to sustained HCV virologic response in the majority of HIV-1-HCV-coinfected patients, regardless of concomitant ART. HIV control was not compromised and no new safety signals were identified. This study supports DCV use in HIV-1-HCV-coinfected patients, while allowing the vast majority of patients to remain on their existing ART regimen.

Dynamic of Mixed HCV Infection in Plasma and PBMC of HIV/HCV Patients Under Treatment With Peg-IFN/Ribavirin.

The extent of mixed hepatitis C virus (HCV) genotype in different compartments (plasma and peripheral blood mononuclear cell, PBMC) and possible association with treatment efficacy in HIV/HCV coinfected patients remains to be unknown.The objective of this study was to elucidate the frequency of mixed genotype infection (MG), its profile in different compartments during anti-HCV treatment, and the possible influence of different genotypes on the response rate.The compartmentalization of HCV population was investigated by next-generation sequencing in 19 HIV/HCV coinfected patients under anti-HCV treatment with peginterferon/ribavirin (P-R). Ten individuals were nonresponder (NR) or relapser (RE) to P-R treatment and 9 had a sustained virological response (SVR).Eleven/nineteen (58%) patients had MG in plasma compartment. Ten or 12 patients infected by a difficult to treat genotype (DTG) 1 or 4 as dominant strain, had an MG, whereas only 1/7 individuals infected by easy to treat genotype (ETG) harbored a mixed genotype, P = 0.006. HCV-RNA was more frequently detected in PBMC of NR (10/10) than in those of SVR (5/9), P = 0.032. Mixed genotype infection was detected in 6/15 (40%) PBMC-positive cases and was not associated with P-R treatment response. By multivariate analysis, MG in plasma samples was the most important viral factor affecting the treatment response (P = 0.0237).Detection of MG in plasma of HIV/HCV coinfected patients seems to represent the major determinant of response to P-R treatment. This finding may have important clinical implication in light of the new therapeutic approach in HIV/HCV coinfected individuals suggesting that combination treatment with direct acting antivirals could be less effective in MG.