Atazanavir-Based Therapy Is Associated with Higher Hepatitis C Viral Load in HIV Type 1-Infected Subjects with Untreated Hepatitis C

Comunicación cortaWe assessed the relationship between atazanavir (ATV)-based antiretroviral treatment (ART) and plasma hepatitis C virus (HCV) viral load in a population of HIV/HCV-coinfected patients. HIV/HCV-coinfected patients who received ART based on a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) were included. Patients were stratified by ART drug [ATV/rtv, lopinavir (LPV/rtv), efavirenz (EFV), nevirapine (NVP), and other PIs], HCV genotype (1/4 and 2/3), and IL28B genotype (CC and non-CC). The Kruskal-Wallis test and chi-squared test were used to compare continuous and categorical variables, respectively. Multivariate analysis consisted of a stepwise linear regression analysis. Six hundred and forty-nine HIV/HCV-coinfected patients were included. HCV genotype 1/4 patients who received ATV had higher HCV RNA levels [6.57 (5.9-6.8) log IU/ml] than those who received LPV [6.1 (5.5-6.5) log IU/ml], EFV [6.1 (5.6-6.4) log IU/ml], NVP [5.8 (5.5-5.9) log IU/ml], or other PIs [6.1 (5.7-6.4) log IU/ml] (p=0.014). This association held for the IL28B genotype (CC versus non-CC). The association was not found in patients carrying HCV genotypes 2/3. The linear regression model identified the IL28B genotype and ATV use as independent factors associated with HCV RNA levels. ATV-based therapy may be associated with a higher HCV RNA viral load in HIV/HCV-coinfected patients

Hepatitis E 3ra genotype infection in people living with HIV in Spain

[Abstract] Background: The objective of our study was to assess the prevalence and incidence of HEV in people living with HIV (PLWH) in a Spanish national cohort. Methods: Retrospective longitudinal study including PLWH recruited in the cohort of adult HIV-infected patients of the AIDS Research Network in follow-up at 28 Spanish hospitals with available serum samples in 2014 and 2015. All samples were tested for HEV IgG, IgM, and RNA. Samples with detectable HEV viral loads were genotyped. Prevalence and incidence of HEV infection were calculated. Results: The study sample comprised 845 PLWH. At baseline, 101 patients were positive for HEV IgG antibodies (11.9%), none had HEV IgM antibodies, and 2 presented detectable HEV RNA (0.23%). Forty-two seroconverted for IgG, supposing a cumulative incidence of 5.7%. One subject was positive for IgM (0.13%), and 2 showed detectable HEV RNA (0.27%). One case was infected by the emergent HEV genotype 3ra. Conclusion: Our study identifies one case of HEV 3ra genotype infection, the main host of which is rabbit, showing a potential zoonotic role of this emerging genotype in Spain.Instituto de Salud Carlos III; RD16/0025/0017Instituto de Salud Carlos III; RD16/0025/0034Instituto de Salud Carlos III; RD16/0025/0040Instituto de Salud Carlos III; RD12/0017/0012Instituto de Salud Carlos III; PI16/01297Junta de Andalucía; PIN-0477-201

Butchering activity is the main risk factor for hepatitis E virus (Paslahepevirus balayani) infection in southwestern Nigeria: a prospective cohort study

IntroductionPaslahepevirus balayani (Hepatitis E virus; HEV) is an emerging virus that poses as a public health threat. The virus is now reported to be the leading cause of acute viral hepatitis, with a unique impact on African settings. Our aim was to evaluate the prevalence and risk factors for HEV infection in three cohorts (animal handlers, villagers, and students).MethodsA prospective cross-sectional study was carried out on a total of 752 subjects from southwestern Nigeria. In all individuals, anti-HEV IgG and anti-HEV IgM antibodies were evaluated by using ELISA (confirming positive results via immunoblotting), and serum viral RNA was evaluated by using two RT-PCR assays.ResultsThe overall seroprevalence of HEV IgG and HEV IgM was 14.9% (95% CI: 12.5–17.6%) and 1.3% (95% CI: 0.7–2.5%), respectively. We observed the highest seroprevalence among animal contact individuals, with butchers being the population with the highest HEV IgG seroprevalence (31.1%). Similarly, HEV IgM was higher in the animal contact group (2.2%) than in the non-animal contact cohort (0%).DiscussionsViral RNA was not detected in any of the samples. Butchering was significantly associated with higher HEV prevalence. Although all efforts to prevent HEV in Africa have focused on the chlorination of water, our study suggests that most new infections could currently be linked to animal manipulation. Therefore, education and guidelines must be provided in southwest Nigeria to ensure that animal handling and processing methods are safe

Ribavirin as a First Treatment Approach for Hepatitis E Virus Infection in Transplant Recipient Patients

The hepatitis E virus (HEV) is the major cause of acute hepatitis of viral origin worldwide. Despite its usual course as an asymptomatic self-limited hepatitis, there are highly susceptible populations, such as those with underlying immunosuppression, which could develop chronic hepatitis. In this situation, implementation of therapy is mandatory in the sense to facilitate viral clearance. Currently, there are no specific drugs approved for HEV infection, but ribavirin (RBV), the drug of choice, is used for off-label treatment. Here, we present two cases of chronic HEV infection in transplant patients, reviewing and discussing the therapeutic approach available in the literature. The use of RBV for the treatment of an HEV infection in organ transplant patients seems to be effective. The recommendation of 12 weeks of therapy is adequate in terms of efficacy. Nevertheless, there are important issues that urgently need to be assessed, such as optimal duration of therapy and drug dosage

The PNPLA3 Genetic Variant rs738409 Influences the Progression to Cirrhosis in HIV/Hepatitis C Virus Coinfected Patients

Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3 gene on liver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymorphisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hundred and thirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determinations without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients who underwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 G allele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.12-3.50). Also, 21 (30.4%) of 69 G allele carriers versus 16 (15.7%) of 102 CC patients showed significant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.23-6.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95% confidence interval = 1.01-11.70). Our results strongly suggest that the rs738409 polymorphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients

Zoonotic "Enterocytozoon bieneusi" genotypes in free-ranging and farmed wild ungulates in Spain

Microsporidia comprises a diverse group of obligate, intracellular, and spore-forming parasites that infect a wide range of animals. Among them, Enterocytozoon bieneusi is the most frequently reported species in humans and other mammals and birds. Data on the epidemiology of E. bieneusi in wildlife are limited. Hence, E. bieneusi was investigated in eight wild ungulate species present in Spain (genera Ammotragus, Capra, Capreolus, Cervus, Dama, Ovis, Rupicapra, and Sus) by molecular methods. Faecal samples were collected from free-ranging (n = 1058) and farmed (n = 324) wild ungulates from five Spanish bioregions. The parasite was detected only in red deer (10.4%, 68/653) and wild boar (0.8%, 3/359). Enterocytozoon bieneusi infections were more common in farmed (19.4%, 63/324) than in wild (1.5%, 5/329) red deer. A total of 11 genotypes were identified in red deer, eight known (BEB6, BEB17, EbCar2, HLJD-V, MWC_d1, S5, Type IV, and Wildboar3) and three novel (DeerSpEb1, DeerSpEb2, and DeerSpEb3) genotypes. Mixed genotype infections were detected in 15.9% of farmed red deer. Two genotypes were identified in wild boar, a known (Wildboar3) and a novel (WildboarSpEb1) genotypes. All genotypes identified belonged to E. bieneusi zoonotic Groups 1 and 2. This study provides the most comprehensive epidemiological study of E. bieneusi in Spanish ungulates to date, representing the first evidence of the parasite in wild red deer populations worldwide. Spanish wild boars and red deer are reservoir of zoonotic genotypes of E. bieneusi and might play an underestimated role in the transmission of this microsporidian species to humans and other animal

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

Hepatitis E Infection in HIV-Infected Patients.

The hepatitis E virus (HEV) represents a major cause of acute hepatitis worldwide. The majority of HEV cases occur in low-income countries, mainly Asia and Africa, where HEV causes large outbreaks associated with the consumption of contaminated water and high mortality in specific populations. In high-income countries, HEV infection is considered a zoonotic disease that is linked to the consumption of contaminated food. Although a high proportion of cases have self-limiting asymptomatic or subclinical infections, immunosuppression may modify the pathogenesis and clinical impact of this emerging disease. Here, we review the current knowledge about the epidemiology, diagnosis, clinical manifestations, management and prevention of HEV infection in HIV-infected subjects. Despite the increasing knowledge about the pathogenesis, epidemiology and clinical impact of HEV infection, several major factors are faced by HIV-infected patients, including treatment recommendations, immunization and risk practices

Role of Hepatitis E Virus Infection in Acute-on-Chronic Liver Failure

Chronic liver disease (CLD) with a variety of causes is currently reported to be one of the main causes of death worldwide. Patients with CLD experience deteriorating liver function and fibrosis, progressing to cirrhosis, chronic hepatic decompensation (CHD), end-stage liver disease (ESLD), and death. Patients may develop acute-on-chronic liver failure (ACLF), typically related to a precipitating event and associated with increased mortality. The objective of this review was to analyze the role of acute hepatitis E virus (HEV) infection in patients with CLD, focusing on the impact of this infection on patient survival and prognosis in several world regions