Novel Therapies in HBV Infection

Current treatments for chronic hepatitis B are able to provide a sustained suppression of the viral replication (i.e., persistent undetectability of HBV DNA). This leads to improvement of liver fibrosis and reduction of clinical complications. However, hepatitis B surface antigen (HBsAg) persists in most patients, probably justifying a still increased risk of hepatocellular carcinoma. Indeed, obtaining a complete and sterilizing cure with elimination of the covalently closed circular DNA (cccDNA) or silencing its activity is still a holy grail. New molecules are under evaluation to suppress viral replication acting on multiple phases of the HBV cycle or improve specific immune response against HBV. Molecules acting on HBV cycle have already showed encouraging results, such as entry inhibitors, small interfering RNAs (siRNAs), capsid assembly modulators (CAMs), nucleic acid polymers (NAPs). Also, promising results have been observed with immune-modulators, therapeutic vaccines, and other immune-based approaches. Among these, toll-like (TLR) or anti-programmed receptor agonists antibody 1 of the cell death protein (PD1) (e.g., nivolumab) are most promising. This paper describes newer drugs appearing on the horizon, including antiviral drugs targeting different steps of the HBV life cycle and therapeutic approaches based on immune-modulation

Ecology of Italian Protura

The ecology of Protura in Italy (including Corsica) is tentatively described according to original and bibliographical data. Protura are quite common but very rarely abundant: their mean density in soil samples collected in Liguria (NW Italy) was estimated to be 372 /m\ub2 (s.d. 657 \u2013 max. 2790 /m\ub2 in a Holm oak forest). Information from the analyses of habitat and/or elevation of 3448 specimens from 269 collections and 4071 specimens from 295 collections identified to species and genus level, respectively, enabled us to outline Protura assemblages for eight different macro-habitats. The unbalanced sex ratio in favour of females observed in 12 of the dominant species of Acerentomata suggests that (based also on the sperm types known in Protura) a single male can fertilize several females through spermatophores. For one species (Proturentomon minimum) only females were collected, which may suggest the possibility of parthenogenesis in some Protura. An analysis of the phenology and population dynamics of the five dominant species, showed annual cycles with one (Acerentomon microrhinus) or more (A. gallicum, A. italicum, A. maius and Eosentomon transitorium) peaks of reproductive activity. Other ecological remarks (e.g. about the relationship between the amplitude of latitudinal/altitudinal distribution and the ecological distribution of Protura in Italy) are discussed

Emergence of Exhausted B Cells in Asymptomatic HIV-1-Infected Patients Naïve for HAART is Related to Reduced Immune Surveillance

Alterations of B cell subpopulations have been described up to date as characterizing advanced stage of HIV-1 infection. However, whether such defects are relevant in subjects with a preserved number of CD4+ T cells (>350 cells/μL) is unclear. In a cross-sectional study, we investigated if signs of B cells exhaustion and impaired viral immune surveillance are present in a cohort of 43 asymptomatic HIV-1-infected patients with preserved CD4+ T cell counts (>350 cells/μL) and highly active antiretroviral therapy (HAART) untreated. A dramatic expansion of exhausted tissue-like memory B cells (CD10−CD21lowCD27−) was observed. B cells alteration was related to an increase in Torque teno virus (TTV) load, used as surrogate marker of immune function. Successfully HAART-treated patients showed normalization of B cell subpopulations frequency and TTV load. These results provide new insights on B cell in HIV-1 infection and show that development of B cell abnormalities precedes CD4+ T cell decline

Dideoxynucleoside HIV reverse transcriptase inhibitors and drug-related hepatotoxicity: a case report

This report regards the case of a 43 year-old HIV-positive woman who developed an episode of serious transaminase elevation during stavudine-including antiretroviral therapy. Diagnostic assessment ruled out hepatitis virus co-infection, alcohol abuse besides other possible causes of liver damage. No signs of lactic acidosis were present. Liver biopsy showed portal inflammatory infiltrate, spotty necrosis, vacuoles of macro- and micro-vesicular steatosis, acidophil and foamy hepatocytes degeneration with organelles clumping, poorly formed Mallory bodies and neutrophil granulocytes attraction (satellitosis). A dramatic improvement in liver function tests occurred when stavudine was discontinued and a new antiretroviral regimen with different nucleoside reverse transcriptase inhibitors was used. The importance of considering hepatotoxicity as an adverse event of HAART including stavudine, even in absence of other signs of mitochondrial toxicity should therefore be underlined. Liver biopsy may provide further important information regarding patients with severe transaminase elevation, for a better understanding of the etiology of liver damage

Heterogeneity and penetration of HIV-1 non-subtype B viruses in an Italian province: Public health implications

SUMMARYThis study assessed changes in prevalence and distribution of HIV-1 non-subtype B viruses in Italian and immigrant patients over two decades in a province in Italy. All HIV-positive patients who underwent genotypic resistance testing were selected. Prevalence of non-subtype B viruses in 3-year periods was calculated. All sequences of non-subtype B and those provided by REGA as unassigned were analysed for phylogenetic relationships. In total, 250/1563 (16%) individuals were infected with a non-subtype B virus. Prevalence increased over time, reaching a peak (31·5%) in 2004–2006. In Italian patients, the most frequent subtypes were B (92·5%) and F1 (4%). F1 subtype was also prevalent in patients from South America (13·6%); in patients of African origin, CRF02_AG (54·9%) and G (12·3%) were the most frequent. HIV-1 non-subtype B infections in Italians were mostly found in patients who acquired HIV sexually. A phylogenetic relationship between F subtypes in Italian and representative HIV-1 sequences from Brazil was found. C subtypes in Italians were phylogenetically related to subtypes circulating in Brazil. Inter-subtype recombinants were also found in the latest years. The HIV-1 epidemic in Brescia province evolved to the point where about 1/3 patients recently diagnosed harboured non-B HIV subtypes. The distribution of HIV-1 non-B subtypes in Italian patients resembled that in South American patients and phylogenetic relatedness between some Italian and South American HIV-1 strains was found. The possible epidemiological link between these two populations would have been missed by looking only at risk factors for HIV acquisition declared by patients. The evidence of inter-subtype recombinants points to significant genetic assortment. Overall our results support phylogenetic analysis as a tool for epidemiological investigation in order to guide targeted prevention strategies

Knowledge of HIV infection and ways of its transmission: a knowledge, attitudes, beliefs and practices (KABP) survey among a sample of students at the “Magna Graecia”, University of Catanzaro

Background. Continuous spreading of HIV infection may be due to a lack of knowledge, especially among young people. Methods. We decided to assess  knowledge of HIV infection and risk factors in a sample of students at the “Magna Graecia” University of Catanzaro, using an anonymous multiple-choice questionnaire. Results. An anonymous multiple-choice questionnaire was administered in December 2015. Two hundred and sixty-six students responded (216 attending the medical school and 50 attending School of Law). Knowledge of HIV infection was scarce in a significant percentage of students who practice behaviours at risk for acquisition of HIV infection and STDs (sexually transmitted diseases) in general. Conclusion. This study shows that preventative and informative campaigns are urgently needed in earlier stage of adolescence to avoid acquisition of HIV infection and other STD

The risk of late or advanced presentation of HIV infected patients is still high, associated factors evolve but impact on overall mortality is vanishing over calendar years: Results from the Italian MASTER Cohort

BACKGROUND: We aimed at evaluating frequency and factors associated with late presentation and advanced HIV disease and excess risk of death due to these conditions from 1985 to 2013 among naïve HIV infected patients enrolled in the Italian MASTER Cohort. METHODS: All antiretroviral naive adults with available CD4+ T cell count after diagnosis of HIV infection were included. Multivariable logistic regression analysis investigated factors associated either with late presentation or advanced HIV disease. Probabilities of survival were estimated both at year-1 and at year-5 according to the Kaplan-Meier method. Flexible parametric models were used to evaluate changes in risk of death overtime according to late presentation and advanced HIV disease. The analyses were stratified for calendar periods. RESULTS: 19,391 patients were included (54 % were late presenters and 37.6 % were advanced presenters). At multivariable analysis, the following factors were positively associated with late presentation: male gender (OR = 1.29), older age (≥55 years vs. <25 years; OR = 7.45), migration (OR = 1.54), and heterosexual risk factor for HIV acquisition (OR = 1.52) or IDU (OR = 1.27) compared to homosexual risk. Survival rates at year-5 increased steadily and reached 92.1 % for late presenters vs. 97.4 % for non-late presenters enrolled in the period 2004-2009. Using flexible parametric models we found a sustained reduction of hazard ratios over time for any cause deaths between late and non-late presenters over time. Similar results were found for advanced HIV disease. CONCLUSION: Screening polices need to be urgently implemented, particularly in most-at-risk categories for late presentation, such as migrants, older patients and those with heterosexual intercourse or IDU as risk factors for HIV acquisition. Although in recent years the impact of late presentation on survival decreased, about 10 % of patients diagnosed in more recent years remains at increased risk of death over a long-term follow-up