Treatment optimisation for hepatitis C in the era of combination direct-acting antiviral therapy: a systematic review and meta-analysis.

Background: Prior to direct-acting antiviral (DAA) therapy, personalised medicine played an important role in the treatment of hepatitis C virus (HCV). Whilst simplified treatment strategies are central to treatment scale-up, some patients will benefit from treatment optimisation. This systematic review and meta-analysis explores treatment optimisation strategies in the DAA era. Methods: We systematically searched Medline, Embase, and Web of Science for studies that adopted a stratified or personalised strategy using a licensed combination DAA regimen, alone or with additional agents. We performed a thematic analysis to classify optimisation strategies and a meta-analysis of sustained virologic response rates (SVR), exploring heterogeneity with subgroup analyses and meta-regression. Results: We included 64 studies (9450 participants). Thematic analysis found evidence of three approaches: duration, combination, and/or dose optimisation. We separated strategies into those aiming to maintain SVR in the absence of predictors of failure, and those aiming to improve SVR in the presence of predictors of failure. Shortened duration regimens achieve pooled SVR rates of 94.2% (92.3-95.9%) for 8 weeks, 81.1% (75.1-86.6%) for 6 weeks, and 63.1% (39.9-83.7%) for ≤4 weeks. Personalised strategies (100% vs 87.6%; p<0.001) and therapy shortened according to ≥3 host/viral factors (92.9% vs 81.4% or 87.2% for 1 or 2 host/viral factors, respectively; p=0.008) offer higher SVR rates when shortening therapy. Hard-to-treat HCV genotype 3 patients suffer lower SVR rates despite treatment optimisation (92.6% vs 98.2%; p=0.001). Conclusions: Treatment optimisation for individuals with multiple predictors of treatment failure can offer high SVR rates. More evidence is needed to identify with confidence those individuals in whom SVR can be achieved with shortened duration treatment.

Aiming at the Global Elimination of Viral Hepatitis: Challenges Along the Care Continuum.

A recent international workshop, organized by the authors, analyzed the obstacles facing the ambitious goal of eliminating viral hepatitis globally. We identified several policy areas critical to reaching elimination targets. These include providing hepatitis B birth-dose vaccination to all infants within 24 hours of birth, preventing the transmission of blood-borne viruses through the expansion of national hemovigilance schemes, implementing the lessons learned from the HIV epidemic regarding safe medical practices to eliminate iatrogenic infection, adopting point-of-care testing to improve coverage of diagnosis, and providing free or affordable hepatitis C treatment to all. We introduce Egypt as a case study for rapid testing and treatment scale-up: this country offers valuable insights to policy makers internationally, not only regarding how hepatitis C interventions can be expeditiously scaled-up, but also as a guide for how to tackle the problems encountered with such ambitious testing and treatment programs.

Risk of Tuberculosis Infection and Disease for Health Care Workers: An Updated Meta-Analysis.

BACKGROUND: Tuberculosis (TB) remains a major challenge to global health. Healthcare workers (HCWs) appear to be at increased risk of TB compared with the general population, despite efforts to scale up infection control and reduce nosocomial TB transmission. This review aims to provide an updated estimate of the occupational risk of latent TB infection (LTBI) and active TB among HCWs compared with the general population. METHODS: A systematic review was performed to identify studies published over the last 10 years reporting TB prevalence or incidence among HCWs and a control group. Pooled effect estimates were calculated to determine the risk of infection. RESULTS: Twenty-one studies met the inclusion criteria, providing data on 30961 HCWs across 16 countries. Prevalence of LTBI among HCWs was 37%, and mean incidence rate of active TB was 97/100000 per year. Compared with the general population, the risk of LTBI was greater for HCWs (odds ratio [OR], 2.27; 95% confidence interval [CI], 1.61-3.20), and the incidence rate ratio for active TB was 2.94 (95% CI, 1.67-5.19). Comparing tuberculin skin test and interferon-gamma release assay, OR for LTBI was found to be 1.72 and 5.61, respectively. CONCLUSIONS: The overall risk of both LTBI and TB to HCWs continues to be significantly higher than that of the general population, consistent with previous findings. This study highlights the continuing need for improvements in infection control and HCW screening programs.

Impact and Cost-Effectiveness of Point-Of-Care CD4 Testing on the HIV Epidemic in South Africa.

Rapid diagnostic tools have been shown to improve linkage of patients to care. In the context of infectious diseases, assessing the impact and cost-effectiveness of such tools at the population level, accounting for both direct and indirect effects, is key to informing adoption of these tools. Point-of-care (POC) CD4 testing has been shown to be highly effective in increasing the proportion of HIV positive patients who initiate ART. We assess the impact and cost-effectiveness of introducing POC CD4 testing at the population level in South Africa in a range of care contexts, using a dynamic compartmental model of HIV transmission, calibrated to the South African HIV epidemic. We performed a meta-analysis to quantify the differences between POC and laboratory CD4 testing on the proportion linking to care following CD4 testing. Cumulative infections averted and incremental cost-effectiveness ratios (ICERs) were estimated over one and three years. We estimated that POC CD4 testing introduced in the current South African care context can prevent 1.7% (95% CI: 0.4% - 4.3%) of new HIV infections over 1 year. In that context, POC CD4 testing was cost-effective 99.8% of the time after 1 year with a median estimated ICER of US$4,468/DALY averted. In healthcare contexts with expanded HIV testing and improved retention in care, POC CD4 testing only became cost-effective after 3 years. The results were similar when, in addition, ART was offered irrespective of CD4 count, and CD4 testing was used for clinical assessment. Our findings suggest that even if ART is expanded to all HIV positive individuals and HIV testing efforts are increased in the near future, POC CD4 testing is a cost-effective tool, even within a short time horizon. Our study also illustrates the importance of evaluating the potential impact of such diagnostic technologies at the population level, so that indirect benefits and costs can be incorporated into estimations of cost-effectiveness.