Search

Background: In economic analyses of HIV interventions, South Africa is often used as a case in point, due to the availability of good epidemiological and programme data and the global relevance of its epidemic. Few analyses however use locally relevant cost data. We reviewed available cost data as part of the South African HIV Investment Case, a modelling exercise to inform the optimal use of financial resources for the country’s HIV programme. Methods: We systematically reviewed publication databases for published cost data covering a large range of HIV interventions and summarised relevant unit costs (cost per person receiving a service) for each. Where no data was found in the literature, we constructed unit costs either based on available information regarding ingredients and relevant public-sector prices, or based on expenditure records. Results: Only 42 (5%) of 1,047 records included in our full-text review reported primary cost data on HIV interventions in South Africa, with 71% of included papers covering ART. Other papers detailed the costs of HCT, MMC, palliative and inpatient care; no papers were found on the costs of PrEP, social and behaviour change communication, and PMTCT. The results informed unit costs for 5 of 11 intervention categories included in the Investment Case, with the remainder costed based on ingredients (35%) and expenditure data (10%). Conclusions: A large number of modelled economic analyses of HIV interventions in South Africa use as inputs the same, often outdated, cost analyses, without reference to additional literature review. More primary cost analyses of non-ART interventions are needed. [ABSTRACT FROM AUTHOR]

Marburg virus disease (MVD) presents a significant global health threat, lacking effective antivirals and with current supportive care offering limited therapeutic options. This mini review explores the emerging landscape of novel antiviral strategies against MVD, focusing on promising therapeutics currently in the development pipeline. We delve into direct-acting antiviral approaches, including small molecule inhibitors targeting viral entry, replication, and assembly, alongside nucleic acid antisense and RNA interference strategies. Host-targeting antivirals are also considered, encompassing immune modulators like interferons and cytokine/chemokine modulators, broad-spectrum antivirals, and convalescent plasma and antibody-based therapies. The paper then examines preclinical and clinical development for the novel therapeutics, highlighting in vitro and in vivo models for antiviral evaluation, safety and efficacy assessments, and the critical stages of clinical trials. Recognizing the challenges of drug resistance and viral escape, the mini review underscores the potential of combination therapy strategies and emphasizes the need for rapid diagnostic tools to optimize treatment initiation. Finally, we discuss the importance of public health preparedness and equitable access to these promising therapeutics in achieving effective MVD control and global health security. This mini review presents a comprehensive overview of the burgeoning field of MVD antivirals, highlighting the potential of these novel approaches to reshape the future of MVD treatment and prevention. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatitis B virus (HBV) affects around 300 million people worldwide and is a significant risk factor for the development of hepatocellular carcinoma (HCC). Nucleos(t)ide analog therapy has aided in decreasing mortality from HBV. However, no cure for HBV currently exists. Despite adequate treatment based on the undetectable viral load or absence of surface protein, there has been much research demonstrating persistent risk for HBV-associated HCC. The aim of this paper is to review the related factors, pathophysiology, and evidence for why this risk exists. Further clarification of the relationship and risk factors for HBV-related HCC is necessary for appropriate screening and the eventual development of a cure. Chronic hepatitis B virus (HBV) infection is the largest global cause of hepatocellular carcinoma (HCC). Current HBV treatment options include pegylated interferon-alpha and nucleos(t)ide analogues (NAs), which have been shown to be effective in reducing HBV DNA levels to become undetectable. However, the literature has shown that some patients have persistent risk of developing HCC. The mechanism in which this occurs has not been fully elucidated. However, it has been discovered that HBV's covalently closed circular DNA (cccDNA) integrates into the critical HCC driver genes in hepatocytes upon initial infection; additionally, these are not targets of current NA therapies. Some studies suggest that HBV undergoes compartmentalization in peripheral blood mononuclear cells that serve as a sanctuary for replication during antiviral therapy. The aim of this review is to expand on how patients with HBV may develop HCC despite years of HBV viral suppression and carry worse prognosis than treatment-naive HBV patients who develop HCC. Furthermore, HCC recurrence after initial surgical or locoregional treatment in this setting may cause carcinogenic cells to behave more aggressively during treatment. Curative novel therapies which target the life cycle of HBV, modulate host immune response, and inhibit HBV RNA translation are being investigated. [ABSTRACT FROM AUTHOR]

Rabies virus (RABV) causes severe neurological symptoms in mammals. The disease is almost inevitably lethal as soon as clinical symptoms appear. The use of rabies immunoglobulins (RIG) and vaccination in post-exposure prophylaxis (PEP) can provide efficient protection, but many people do not receive this treatment due to its high cost and/or limited availability. Highly potent small molecule antivirals are urgently needed to treat patients once symptoms develop. In this paper, we report on the development of a high-throughput phenotypic antiviral screening assay based on the infection of BHK-21 cells with a fluorescent reporter virus and high content imaging readout. The assay was used to screen a repurposing library of 3681 drugs (all had been studied in phase 1 clinical trials). From this series, salinomycin was found to selectively inhibit viral replication by blocking infection at the entry stage. This shows that a high-throughput assay enables the screening of large compound libraries for the purposes of identifying inhibitors of RABV replication. These can then be optimized through medicinal chemistry efforts and further developed into urgently needed drugs for the treatment of symptomatic rabies. [ABSTRACT FROM AUTHOR]

Co-diagnosis of HIV and tuberculosis presents a treatment dilemma. Starting both treatments at the same time can cause a flood of immune response called immune reconstitution inflammatory syndrome (IRIS) which can be lethal. But, how long to delay HIV treatment is less understood. In 2011, based on the conclusions of three separate studies, WHO recommended starting HIV treatment earlier for those with later HIV disease progression. This paper conducts a replication study of one of the three studies, by Havlir and colleagues. Using their publicly available data, we were able to replicate most of the results presented in the original paper. In our measurement and estimation analyses we use different estimation techniques to assess the robustness of the results. We find that adjusting for loss to follow-up does not affect the main results of the paper. However, an ANCOVA estimation and an instrumental variable model weaken the main result of the paper of better outcomes with early HIV treatment only for those who are sicker, reducing significance from the 5% to the 10% level. A change-point analysis also detects no changes in effect by timing of HIV treatment initiation or different thresholds of CD4 count for the primary outcome. This result suggests that the choice of start time for HIV treatment initiation should be based on other factors including potential drug interactions, overlapping side effects, a high pill burden and severity of illness rather than CD4 threshold and preset timeframes. While we caution against overgeneralizing, the result of this replication is aligned with more recent studies that show no evidence that early initiation of HIV treatment reduces mortality for any patients. [ABSTRACT FROM AUTHOR]

Terminal nucleotidyltransferases (TENTs) could generate a 'mixed tail' or 'U-rich tail' consisting of different nucleotides at the 3′ end of RNA by non-templated nucleotide addition to protect or degrade cellular messenger RNA. Recently, there has been increasing evidence that the decoration of virus RNA terminus with a mixed tail or U-rich tail is a critical way to affect viral RNA stability in virus-infected cells. This paper first briefly introduces the cellular function of the TENT family and non-canonical tails, then comprehensively reviews their roles in virus invasion and antiviral immunity, as well as the significance of the TENT family in antiviral therapy. This review will contribute to understanding the role and mechanism of non-canonical RNA tailing in survival competition between the virus and host. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to rapid vaccine development and large global vaccination schemes. However, patients with immune-mediated kidney disease, chronic kidney diseases and kidney transplant recipients show high non-response rates to vaccination despite more than three vaccinations and, consequently, reduced viral clearance capacity when infected while receiving certain immunosuppressants, carrying an elevated risk for coronavirus disease 2019 (COVID-19)-related morbidity and mortality. SARS-CoV-2 evolution has been characterized by the emergence of novel variants and spike mutations contributing to waning efficacy of neutralizing antibodies. To this end, the therapeutic field expands from vaccination towards a combined approach of immunization, pre-exposure prophylaxis and early post-exposure treatment using direct-acting antivirals and neutralizing monoclonal antibodies to treat early in the disease course and avoid hospitalization. This expert opinion paper from the Immunonephrology Working Group of the European Renal Association (ERA-IWG) summarizes available prophylactic and/or early treatment options (i.e. neutralizing monoclonal antibodies and direct-acting antivirals) of SARS-CoV-2-infected patients with immune-mediated kidney disease, chronic kidney disease and kidney transplant recipients. [ABSTRACT FROM AUTHOR]

A hepatitis B or C virus (HBV or HCV) epidemic model with intra- and extra-hepatic coinfection, immune delay and saturation incidence, as well as antiviral therapy is proposed in this paper. The existence of equilibria (infection-free, immune-free and immune-activated), the basic reproduction numbers, i.e., R 0 , R 1 , are given respectively, by which the criteria on (local and global) stability of above equilibria are established. Furthermore, if the immune delay τ > τ 0 , both the existence of subcritical (supercritical) Hopf bifurcation on the immune-activated equilibrium E ∗ , and the stability of bifurcating periodic solutions are obtained. Finally, the theoretical results are demonstrated by numerical simulations. We derive that the immune delay and intra- and extra-hepatic coinfection have significant influence on the transmission of HBV/HCV, could cause more complicated dynamics at E ∗ from stability to unstablity untill bifurcation, which greatly increases the difficulty of disease control. While effective antiviral therapy could evidently decrease the spread of HBV/HCV. [ABSTRACT FROM AUTHOR]

Hepatitis A and hepatitis E are relatively common causes of liver disease. Both viruses are mainly transmitted through the faecal–oral route and, consequently, most outbreaks occur in countries with poor sanitation. An important role of the immune response as the driver of liver injury is also shared by the two pathogens. For both the hepatitis A (HAV) and hepatitis E (HEV) viruses, the clinical manifestations of infection mainly consist of an acute disease with mild liver injury, which results in clinical and laboratory alterations that are self-limiting in most cases. However, severe acute disease or chronic, long-lasting manifestations may occur in vulnerable patients, such as pregnant women, immunocompromised individuals or those with pre-existing liver disease. Specifically, HAV infection rarely results in fulminant hepatitis, prolonged cholestasis, relapsing hepatitis and possibly autoimmune hepatitis triggered by the viral infection. Less common manifestations of HEV include extrahepatic disease, acute liver failure and chronic HEV infection with persistent viraemia. In this paper, we conduct a non-systematic review of the available literature to provide a comprehensive understanding of the state of the art. Treatment mainly consists of supportive measures, while the available evidence for aetiological treatment and additional agents in severe disease is limited in quantity and quality. However, several therapeutic approaches have been attempted: for HAV infection, corticosteroid therapy has shown outcome improvement, and molecules, such as AZD 1480, zinc chloride and heme oxygenase-1, have demonstrated a reduction in viral replication in vitro. As for HEV infection, therapeutic options mainly rely on the use of ribavirin, and some studies utilising pegylated interferon-alpha have shown conflicting results. While a vaccine for HAV is already available and has led to a significant reduction in the prevalence of the disease, several vaccines for HEV are currently being developed, with some already available in China, showing promising results. [ABSTRACT FROM AUTHOR]

With the extension of the COVID-19 pandemic, the large use of COVID-19 vaccines among adults and the emergence of SARS-CoV-2 variants means that the epidemiology of COVID-19 in pediatrics, particularly among younger children, has substantially changed. The prevalence of pediatric COVID-19 significantly increased, several severe cases among children were reported, and long-COVID in pediatric age was frequently observed. The main aim of this paper is to discuss which types of treatment are presently available for pediatric patients with COVID-19, which of them are authorized for the first years of life, and which are the most important limitations of COVID-19 therapy in pediatric age. Four different antivirals, remdesivir (RVD), the combination nirmatrelvir plus ritonavir (Paxlovid), molnupiravir (MPV), and the monoclonal antibody bebtelovimab (BEB), are presently approved or authorized for emergency use for COVID-19 treatment by most of the national health authorities, although with limitations according to the clinical relevance of disease and patient's characteristics. Analyses in the literature show that MPV cannot be used in pediatric age for the risk of adverse events regarding bone growth. The other antivirals can be used, at least in older children, and RDV can be used in all children except in neonates. However, careful research on pharmacokinetic and clinical data specifically collected in neonates and children are urgently needed for the appropriate management of pediatric COVID-19. [ABSTRACT FROM AUTHOR]

Anti-viral therapy is comparatively very effective for patients who get affected by the hepatitis B virus. It is of prime importance to understand the different relations among the viruses, immune responses and overall health of the liver. In this paper, mathematical modeling is done to analyze and understand the effect of antiviral therapy using LHAM which describes the possible relation to HBV and target liver cells. The numerical simulations and error analysis are done up to a sixth-order approximation with the help of Matlab. This paper analyzes how the number of infected cells largely gets reduced and also how the liver damage can be controlled. Therefore, the treatment is successful for HBV infected patients. [ABSTRACT FROM AUTHOR]

Background: CD4 cell counts is widely used as a biomarker for treatment progression when studying the efficacy of drugs to treat HIV-infected patients. In the past, it had been also used in determining eligibility to initiate antiretroviral therapy. The main aim of this was to model the evolution of CD4 counts over time and use this model for an early prediction of subject-specific time to cross a pre-specified CD4 threshold. Methods: Hospital based retrospective cohort study of HIV-infected patients was conducted from January 2009 to December 2014 at University of Gondar hospital, Northwest Ethiopia. Fractional polynomial random effect model is used to model the evolution of CD4 counts over time in response to treatment and to estimate the individual probability to be above a pre-selected CD4 threshold. Human subject research approval for this study was received from University of Gondar Research Ethics Committee and the medical director of the hospital. Results: A total of 1347 patients were included in the analysis presented in this paper. The cohort contributed a total of 236.58 per 100 person-years of follow-up. Later the data were divided into two periods: the first is the estimation period in which the parameters of the model are estimated and the second is the prediction period. Based on the parameters from the estimation period, model based prediction for the time to cross a threshold was estimated. The correlations between observed and predicted values of CD4 levels in the estimation period were 0.977 and 0.982 for Neverapine and Efavirenz containing regimens, respectively; while the correlation between the observed and predicted CD4 counts in the prediction period are 0.742 and 0.805 for NVP and EFV, respectively. Conclusions: The model enables us to estimate a subject-specific expected time to cross a CD4 threshold and to estimate a subject-specific probability to have CD4 count above a pre-specified threshold at each time point. By predicting long-term outcomes of CD4 count of the patients one can advise patient about the potential ART benefits that accrue in the long-term. [ABSTRACT FROM AUTHOR]

Recent advances in the efficacy and tolerability of hepatitis C treatments and the introduction of a universal access scheme for the new Direct Acting Antiviral (DAA) therapies in March 2016, has resulted in a rapid increase in the uptake of hepatitis C treatment in Australia. Despite these positive developments, recent data suggest a plateauing of treatment numbers, indicating that more work may need to be done to identify and address ongoing barriers to hepatitis C treatment access and uptake. This paper aims to contribute to our understanding of the ongoing barriers to DAA therapies, with a focus on people who inject drugs. The paper draws on participant interview data from a qualitative research study based on a participatory research design that included a peer researcher with direct experience of both hepatitis C DAA treatment and injecting drug use at all stages of the research process. The study’s findings show that residual barriers to DAA treatment exist at personal, provider and system levels and include poor venous access, DAA treatments not considered ‘core-business’ by opioid substitution treatment (OST) providers, and patients having to manage multiple health and social priorities that interfere with keeping medical appointments such as childcare and poor access to transport services. Further, efforts to increase access to and uptake of DAA hepatitis C treatment over time will require a focus on reducing stigma and discrimination towards people who inject drugs as this remains as a major barrier to care for many people. [ABSTRACT FROM AUTHOR]

Background/aim: The aim of this descriptive article is to share the experience in Ege University, Turkey with favipiravir in the treatment of severe SARS-CoV-2 pneumonia. Materials and methods: This retrospective descriptive study included patients diagnosed with COVID-19 who presented with or developed severe pneumonia. Results: Forty patients who completed a full course (at least 5 days) of favipiravir were included in the study. At baseline, 30 (75%) patients required treatment for respiratory distress. Thirty-three patients (82.5%) were discharged from the hospital with full recovery, 6 patients (15%) died and 1 case (2.5%) was still at the intensive care unit (ICU) when this paper was written. Conclusion: This study provides relevant information for the treatment of COVID-19, suggesting that favipiravir was associated with significant clinical and laboratory improvements in the majority of the patients, is a safe drug with no serious side effects and would merit further investigation. [ABSTRACT FROM AUTHOR]

Hepatitis B core-related antigen (HBcrAg) is a new biomarker for chronic hepatitis B (CHB) whose performance has not been critically or systematically appraised. Herein, we performed a systematic review to determine its clinical utility. We evaluated the biological pathway of HBcrAg and performed a systematic review of PubMed for clinical trials, cohort studies, and case-control studies that evaluated the clinical utility of HBcrAg. The effectiveness of HBcrAg in predicting HBV-specific clinical events (e.g. HBeAg seroconversion, phases of CHB, HBsAg loss, treatment response, and relapse after stopping therapy) was examined using receiver-operating characteristic curves. The correlation coefficients of HBcrAg with HBV DNA, quantitative HBsAg (qHBsAg), HBV RNA, and cccDNA were summarised from published studies. Median values were used as estimates. HBcrAg consists of three precore/core protein products: HBcAg, HBeAg, and a 22 kDa precore protein. HBcrAg assays have been associated with false-positive rates of 9.3% and false-negative rates of between 12-35% for CHB. The new iTACT-HBcrAg is more sensitive but does not reduce the false-positive rate. A PubMed search found 248 papers on HBcrAg, of which 59 were suitable for analysis. The clinical performance of HBcrAg was evaluated using AUROC analyses, with median AUROCs of 0.860 for HBeAg seroconversion, 0.867 for predicting HBeAg(-) hepatitis, 0.645 for HBsAg loss, 0.757 for treatment response, and 0.688 for relapse after stopping therapy. The median correlation coefficient (r) was 0.630 with HBV DNA, 0.414 with qHBsAg, 0.619 with HBV RNA and 0.550 with cccDNA. Correlation decreased during antiviral therapy, but combined biomarkers improved performance. HBcrAg has a mixed performance and has a poor correlation with HBsAg loss and antiviral therapy, hence HBcrAg results should be interpreted with caution. Hepatitis B core-related antigen (HBcrAg) has been used to assess management of patients with chronic hepatitis B (CHB) without a systematic and critical Sreview of its performance. Our finding that HBcrAg had a false-positive rate of 9% and a false-negative rate of 12-35% raises concerns, although larger studies are needed for validation. A systematic review showed that the performance of HBcrAg was variable depending on the CHB endpoint; it was excellent at predicting HBeAg seroconversion and HBeAg-negative chronic hepatitis (vs. chronic infection), which should be its main use, but it was poor for relapse after stopping antiviral therapy and for HBsAg loss. HBcrAg results should be interpreted with considerable caution, particularly by physicians, researchers, guideline committees and agencies that approve diagnostic tests. [Display omitted] • The biological pathway of HBcrAg is distinct to that of HBsAg. • HBcrAg are translation products from precore and pregenomic RNA comprising HBV core antigen, p22cr and HBeAg. • HBeAg contributes >70% to HBcrAg in HBeAg-positive patients, but its components are non-quantifiable in HBeAg-negative patients. • HBcrAg exhibits variable clinical performance. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is a life-threatening virus that causes very serious liver-related diseases from the family of Hepadnaviridae having very rare qualities resembling retroviruses. In this paper, we analyze the effect of antiviral therapy through mathematical modeling by using Liao's homotopy analysis method (LHAM) that defines the connection between the target liver cells and the HBV. We also examine the basic nonlinear differential equation by LHAM to get a semi-analytical solution. This can be a very straight and direct method which provides the appropriate solution. Moreover, the local and global stability analysis of disease-free and endemic equilibrium is done using Lyapunov function. Mathematica 12 software is used to find out the solutions and graphical representations. We also discuss the numerical simulations up to sixth-order approximation and error analysis using the same software. [ABSTRACT FROM AUTHOR]

There is a substantial interest in detailed models of viral infection and antiviral drug kinetics in order to optimize the treatment against viruses such as HIV. In this paper, we study within-viral dynamics under general intracellular distributed delays and periodic combination antiviral therapy. The basic reproduction number R 0 is established as a global threshold determining extinction versus persistence, and spectral methods are utilized for analytical and numerical computations of R 0 . We derive the critical maturation delay for virus and optimal phase difference between sinusoidally varying drug efficacies under various intracellular delays. Furthermore, numerical simulations are conducted utilizing realistic pharmacokinetics and gamma-distributed viral production delays for HIV. Our results demonstrate that the relative timing of the key viral replication cycle steps and periodic antiviral treatment schedule involving distinct drugs all can interact to critically affect the overall viral dynamics. [ABSTRACT FROM AUTHOR]

Background: Quality improvement collaboratives (QICs) have been used to improve health care for decades. Evidence on QIC effectiveness has been reported, but systematic reviews to date have little information from low- and middle-income countries (LMICs). Objective: To assess the effectiveness of QICs in LMICs. Methods: We conducted a systematic review following Cochrane methods, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for quality of evidence grading, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement for reporting. We searched published and unpublished studies between 1969 and March 2019 from LMICs. We included papers that compared usual practice with QICs alone or combined with other interventions. Pairs of reviewers independently selected and assessed the risk of bias and extracted data of included studies. To estimate strategy effectiveness from a single study comparison, we used the median effect size (MES) in the comparison for outcomes in the same outcome group. The primary analysis evaluated each strategy group with a weighted median and interquartile range (IQR) of MES values. In secondary analyses, standard random-effects meta-analysis was used to estimate the weighted mean MES and 95% confidence interval (CI) of the mean MES of each strategy group. This review is registered with PROSPERO (International Prospective Register of Systematic Reviews): CRD42017078108. Results: Twenty-nine studies were included; most (21/29, 72.4%) were interrupted time series studies. Evidence quality was generally low to very low. Among studies involving health facility-based health care providers (HCPs), for “QIC only”, effectiveness varied widely across outcome groups and tended to have little effect for patient health outcomes (median MES less than 2 percentage points for percentage and continuous outcomes). For “QIC plus training”, effectiveness might be very high for patient health outcomes (for continuous outcomes, median MES 111.6 percentage points, range: 96.0 to 127.1) and HCP practice outcomes (median MES 52.4 to 63.4 percentage points for continuous and percentage outcomes, respectively). The only study of lay HCPs, which used “QIC plus training”, showed no effect on patient care-seeking behaviors (MES -0.9 percentage points), moderate effects on non-care-seeking patient behaviors (MES 18.7 percentage points), and very large effects on HCP practice outcomes (MES 50.4 percentage points). Conclusions: The effectiveness of QICs varied considerably in LMICs. QICs combined with other invention components, such as training, tended to be more effective than QICs alone. The low evidence quality and large effect sizes for QIC plus training justify additional high-quality studies assessing this approach in LMICs. [ABSTRACT FROM AUTHOR]

Interferon-based therapies were until recently the standard of care in chronic hepatitis C (CHC), despite their side eff ects. We aimed to review the available data on the depression and suicide in CHC patients receiving or not antiviral therapy based on interferon treatment. A PubMed search was performed, identifying relevant papers published between 1991 and January 2015 concerning major depressive disorders and suicidal risk in patients under interferon. A total of 21 relevant papers were retrieved. Prospective studies reported depression as the most common side eff ect of interferon, with an incidence peak between weeks 8 and 12 of therapy. Suicide risk was analyzed in 7 of the reviewed articles, and case reports of attempted suicide were discussed. Moreover, studies have shown that pretreatment with serotonin reuptake inhibitors is a good strategy for the prevention of interferon-induced depression. [ABSTRACT FROM AUTHOR]

The global burden of hepatitis B virus (HBV) infection remains high, with chronic hepatitis B (CHB) patients facing a significantly increased risk of developing cirrhosis and hepatocellular carcinoma (HCC). The ultimate objective of antiviral therapy is to achieve a sterilizing cure for HBV. This necessitates the elimination of intrahepatic covalently closed circular DNA (cccDNA) and the complete eradication of integrated HBV DNA. This review aims to summarize the oncogenetic role of HBV integration and the significance of clearing HBV integration in sterilizing cure. It specifically focuses on the molecular mechanisms through which HBV integration leads to HCC, including modulation of the expression of proto-oncogenes and tumor suppressor genes, induction of chromosomal instability, and expression of truncated mutant HBV proteins. The review also highlights the impact of antiviral therapy in reducing HBV integration and preventing HBV-related HCC. Additionally, the review offers insights into future objectives for the treatment of CHB. Current strategies for HBV DNA integration inhibition and elimination include mainly antiviral therapies, RNA interference and gene editing technologies. Overall, HBV integration deserves further investigation and can potentially serve as a biomarker for CHB and HBV-related HCC. [ABSTRACT FROM AUTHOR]

Invasive cervical cancer is the most prevalent cancer among women in Sub-Saharan Africa. In 2013, the World Health Organization (WHO) emitted recommendations to start Highly Active Antiretroviral Therapy (HAART) regardless of CD4 count. Although HAART has been shown to reduce the prevalence of high-risk human papillomavirus (HR-HPV) genotypes, it is unclear whether it confers a protective effect specifically for HPV 16. This review summarizes the existing evidence regarding the effect of HAART on HPV 16 infection, as this genotype may not be influenced by immunity level and explores its implications for Sub Saharan Africa. A comprehensive literature review was undertaken and quality assessment was carried out on the selected papers. Four cohort studies and three cross-sectional studies were identified for which the overall quality score assessment ranged from weak/moderate (Score of 1.8) to strong (Score of 3). The evidence yielded by our review was conflicting. Thus, the high heterogeneity between study populations and results did not allow us to draw any firm conclusions as to whether HAART has an impact on HPV 16 acquisition/prevalence. As only three studies were conducted in Africa, there are insufficient grounds for solid comparison between geographic regions. In light of inadequate data, HPV unvaccinated women on HAART should still receive more frequent follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Treatment of chronic hepatitis C has considerably improved in the last few years thanks to the introduction of direct-acting antivirals able to achieve sustained virological response in more than 95% of patients. Successful anti-HCV treatment can halt liver disease progression and solve the HCV-related extra-hepatic manifestations, eventually reducing liver-related and overall mortality. Areas covered: With the aim to respond to unmet needs in patient's identification, universal access to antiviral therapy and treatment optimization in specific setting of HCV-infected patients, a group of Italian experts met in Stresa in May 2018. The summary of the considerations arising from this meeting and the final statements are reported in this paper. Expert commentary: All the advances on HCV cure may have a real clinical impact not only in individual patients but also at the social health level if they are applied to all infected patients, independently from the stage of liver disease. Further improvements are needed in order to attain HCV elimination, such as the development of an enhanced screening program working in parallel to the present treatment options. [ABSTRACT FROM AUTHOR]

Background: Although empirical evidence suggests that the adherence club model is more effective in retaining people living with HIV in antiretroviral treatment care and sustaining medication adherence compared to standard clinic care, it is poorly understood exactly how and why this works. In this paper, we examined and made explicit how, why and for whom the adherence club model works at a public health facility in South Africa. Methods: We applied an explanatory theory-building case study approach to examine the validity of an initial programme theory developed a priori. We collected data using a retrospective cohort quantitative design to describe the suppressive adherence and retention in care behaviours of patients on ART using Kaplan-Meier methods. In conjunction, we employed an explanatory qualitative study design using non-participant observations and realist interviews to gain insights into the important mechanisms activated by the adherence club intervention and the relevant contextual conditions that trigger the different mechanisms to cause the observed behaviours. We applied the retroduction logic to configure the intervention-context-actor-mechanism-outcome map to formulate generative theories. Results: A modified programme theory involving targeted care for clinically stable adult patients (18 years+) receiving antiretroviral therapy was obtained. Targeted care involved receiving quick, uninterrupted supply of antiretroviral medication (with reduced clinic visit frequencies), health talks and counselling, immediate access to a clinician when required and guided by club rules and regulations within the context of adequate resources, and convenient (size and position) space and proper preparation by the club team. When grouped for targeted care, patients feel nudged, their self-efficacy is improved and they become motivated to adhere to their medication and remain in continuous care. Conclusion: This finding has implications for understanding how, why and under what health system conditions the adherence club intervention works to improve its rollout in other contexts. [ABSTRACT FROM AUTHOR]

Copyright of China Tropical Medicine is the property of China Tropical Medicine Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Homebased index case HIV testing (HHTC) has shown higher uptake and good yield than traditional HIV testing methods. World Health Organization has called for increased operational research to evaluate HIV care processes particularly linkage to care. In this paper, we present project results of the time taken to link newly identified PLHIV to care after HHTC in the Manicaland and Midlands provinces of Zimbabwe. Methods: We retrospectively reviewed community-facility referral data from the Zimbabwe HIV Care and Treatment project for newly diagnosed PLHIV for the period March–September 2016. A referral slip was given to a client after receiving a positive HIV results and was presented and filed upon reaching a health facility. In July 2016, the project started working with trained expert clients to assist with linkage to care. Data was entered in a spreadsheet and then imported for descriptive statistical analysis with EpiInfoTM Version 7.2.0.1. Odd ratios were used to identify factors associated with linkage to care within seven days. Results: Out of 1004 newly identified PLHIV between March and September 2016, 650 (64.7%) were linked to care. The median time taken to be linked to care was four days (Interquartile range 19 days). Overall, 63.1% (410) of PLHIV were linked to care within seven days of diagnosis and 85% within 30 days. PLHIV were more likely to be linked to care within seven days of diagnosis between July and September 2016 (OR = 4.1; p< 0.001), a period when ZHCT started working with expert clients to support linkage to care. Conclusion: HHTC resulted in almost 63% of newly diagnosed PLHIV being linked into care within seven days, and 85% within 30 days. Linkage to care within seven days was significantly associated with the period of engaging expert clients in the project. We recommend community based HIV testing programs to work with expert clients to ensure timely linkages of new PLHIV. [ABSTRACT FROM AUTHOR]

Current estimates of the HIV epidemic indicate a decrease in the incidence of the disease in the undiagnosed subpopulation over the past 10 years. However, a lack of access to care has not been considered when modeling the population. Populations at high risk for contracting HIV are twice as likely to lack access to reliable medical care. In this paper, we consider three contributors to the HIV population dynamics: at-risk population exhaustion, lack of access to care, and usage of anti-retroviral therapy (ART) by diagnosed individuals. An extant problem in the mathematical study of this system is deriving parameter estimates due to a portion of the population being unobserved. We approach this problem by looking at the proportional change in the infected subpopulations. We obtain conservative estimates for the proportional change of the infected subpopulations using hierarchical Bayesian statistics. The estimated proportional change is used to derive epidemic parameter estimates for a system of stochastic differential equations (SDEs). Model fit is quantified to determine the best parametric explanation for the observed dynamics in the infected subpopulations. Parameter estimates derived using these methods produce simulations that closely follow the dynamics observed in the data, as well as values that are generally in agreement with prior understanding of transmission and diagnosis rates. Simulations suggest that the undiagnosed population may be larger than currently estimated without significantly affecting the population dynamics. [ABSTRACT FROM AUTHOR]

Viral infections are one of the major causes of death worldwide, with HIV infection alone resulting in over 1.2 million casualties per year. Antiviral drugs are now being administered for a variety of viral infections, including HIV, hepatitis B and C, and influenza. These therapies target a specific phase of the virus’s life cycle, yet their ultimate success depends on a variety of factors, such as adherence to a prescribed regimen and the emergence of viral drug resistance. The epidemiology and evolution of drug resistance have been extensively characterized, and it is generally assumed that drug resistance arises from mutations that alter the virus’s susceptibility to the direct action of the drug. In this paper, we consider the possibility that a virus population can evolve towards synchronizing its life cycle with the pattern of drug therapy. The periodicity of the drug treatment could then allow for a virus strain whose life cycle length is a multiple of the dosing interval to replicate only when the concentration of the drug is lowest. This process, referred to as “drug tolerance by synchronization”, could allow the virus population to maximize its overall fitness without having to alter drug binding or complete its life cycle in the drug’s presence. We use mathematical models and stochastic simulations to show that life cycle synchronization can indeed be a mechanism of viral drug tolerance. We show that this effect is more likely to occur when the variability in both viral life cycle and drug dose timing are low. More generally, we find that in the presence of periodic drug levels, time-averaged calculations of viral fitness do not accurately predict drug levels needed to eradicate infection, even if there is no synchronization. We derive an analytical expression for viral fitness that is sufficient to explain the drug-pattern-dependent survival of strains with any life cycle length. We discuss the implications of these findings for clinically relevant antiviral strategies. [ABSTRACT FROM AUTHOR]

Background: The WHO HIV Treatment Guidelines suggest routine viral-load monitoring can be used to differentiate antiretroviral therapy (ART) delivery and reduce the frequency of clinic visits for patients stable on ART. This recommendation was informed by economic analysis that showed the approach is very likely to be cost-effective, even in the most resource constrained of settings. The health benefits were shown to be modest but the costs of introducing and scaling up viral load monitoring can be offset by anticipated reductions in the costs of clinic visits, due to these being less frequent for many patients. Key issues for economic evaluation: The cost-effectiveness of introducing viral-load informed differentiated care depends upon whether cost reductions are possible if the number of clinic visits is reduced and/or how freed clinic capacity is used for alternative priorities. Where freed resources, either physical or financial, generate large health gains (e.g. if committed to patients failing ART or to other high value health care interventions), the benefits of differentiated care are expected to be high; if however these freed physical resources are already under-utilized or financial resources are used less efficiently and would not be put to as beneficial an alternative use, the policy may not be cost-effective. The implication is that the use of conventional unit costs to value resources may not well reflect the latter’s value in contributing to health improvement. Analyses intended to inform resource allocated decisions in a number of settings may therefore have to be interpreted with due consideration to local context. In this paper we present methods of how economic analyses can reflect the real value of health care resources rather than simply applying their unit costs. The analyses informing the WHO Guidelines are re-estimated by implementing scenarios using this framework, informing how differentiated care can be prioritized to generate greatest gains in population health. Implications: The findings have important implications for how economic analyses should be undertaken and reported in HIV and other disease areas. Results provide guidance on conditions under which viral load informed differentiated care will more likely prove to be cost effective when implemented. [ABSTRACT FROM AUTHOR]