Behavioural, not biological, factors drive the HCV epidemic among HIV-positive MSM: HCV and HIV modelling analysis including HCV treatment-as-prevention impact.

Background: Uncertainty surrounds why hepatitis C virus (HCV) is concentrated among HIV-positive men who have sex with men (MSM). We used mathematical modelling to explore reasons for these infection patterns, and implications for HCV treatment-as-prevention. Methods: Using a joint MSM HIV/HCV transmission model parameterized with UK behavioural data, we considered how biological (heightened HCV infectivity and reduced spontaneous clearance among HIV-positive MSM) and/or behavioural factors (preferential sexual mixing by HIV status and risk heterogeneity) could concentrate HCV infection in HIV-positive MSM as commonly observed (5-20 times the HCV prevalence in HIV-negative MSM; defined as the HCV ratio). We explored how HCV treatment-as-prevention impact varies under differing HCV ratios. Results: Biological factors produced low HCV ratios ( 10) that were highly sensitive to both factors. Irrespective of the HCV ratio or behavioural/biological factors, HCV treatment of HIV-diagnosed MSM markedly reduced the HCV prevalence among HIV-positive MSM, but less impact was achieved among all MSM for lower HCV ratios. Conclusions: Sexual behaviour patterns likely drive observed HCV infection patterns among HIV-positive MSM. Changes in these patterns could disseminate HCV amongst HIV-negative MSM, limiting the impact of targeting HCV treatment to HIV-diagnosed MSM

Scaling up screening and treatment for elimination of hepatitis C among men who have sex with men in the era of HIV pre-exposure prophylaxis.

BACKGROUND: Routine HIV pre-exposure prophylaxis (PrEP) and HIV care appointments provide opportunities for screening men who have sex with men (MSM) for hepatitis C virus infection (HCV). However, levels of screening required for achieving the WHO elimination target of reducing HCV incidence by 90% by 2030 among all MSM are unknown. METHODS: An HCV/HIV transmission model was calibrated to UK prevalence of HIV among MSM (4·7%) and chronic HCV infection among HIV-positive MSM (9·9%) and HIV-negative MSM (1.2%). Assuming 12·5% coverage of PrEP among HIV-negative MSM, we evaluated the relative reduction in overall HCV incidence by 2030 (compared to 2018 levels) of HCV screening every 12/6-months (alongside completing direct acting antiviral treatment within 6-months of diagnosis) in PrEP users and/or HIV-diagnosed MSM. We estimated the additional screening required among HIV-negative non-PrEP users to reduce overall incidence by 90% by 2030. The effect of 50% reduction in condom use among PrEP users (risk compensation) was estimated. RESULTS: Screening and treating PrEP users for HCV every 12 or 6-months decreases HCV incidence by 67·3% (uncertainty range 52·7-79·2%) or 70·2% (57·1-80·8%), respectively, increasing to 75·4% (59·0-88·6%) or 78·8% (63·9-90·4%) if HIV-diagnosed MSM are also screened at same frequencies. Risk compensation reduces these latter projections by <10%. To reduce HCV incidence by 90% by 2030 without risk compensation, HIV-negative non-PrEP users require screening every 5·6 (3·8-9·2) years if MSM on PrEP and HIV-diagnosed MSM are screened every 6-months, shortening to 4·4 (3·1-6·6) years with risk compensation. For 25·0% PrEP coverage, the HCV elimination target can be reached without screening HIV-negative MSM not on PrEP, irrespective of risk compensation. INTERPRETATION: At low PrEP coverage, increased screening of all MSM is required to achieve the WHO HCV-elimination targets for MSM in the UK, whereas at higher PrEP coverage this is possible through just screening HIV-diagnosed MSM and PrEP users

Physical Limnology and Sediment Dynamics of Lago Argentino, the World's Largest Ice-Contact Lake

Proglacial lakes, whose numbers have been growing around the world, may drive accelerated glacier retreat and provide valuable records of past glacier and climatic changes. Despite their importance, few studies have investigated the sedimentary properties and processes acting within large proglacial lakes. Lago Argentino (LArg) is a 1,500 km2 ice-contact lake on the eastern flank of the Southern Patagonian Icefield. Here, we describe the results from a detailed analysis of 47 sediment cores obtained throughout this lake basin, supplemented with remotely sensed data. We show that: (a) LArg exhibits a seasonal variation in sediment properties (varves); (b) varve formation results from three distinct processes, driven by seasonal changes in glacial sediment input, seasonal changes in fluvial sediment input, and seasonal variations in lake mixing; and (c) distance from glacier calving fronts provides the first-order control on sediment grain size and accumulation rate. Our findings highlight the exceptional preservation of annual laminations within proglacial lakes, their potential for reconstructing past glacier changes, and their relevance for forecasting future glacier–lake interactions.Fil: Van Wyk de Vries, Maximillian. University of Minnesota; Estados UnidosFil: Ito, Emi. University of Minnesota; Estados UnidosFil: Shapley, Mark. University of Minnesota; Estados UnidosFil: Brignone, Guido. Universidad Nacional de Córdoba; ArgentinaFil: Romero, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Wickert, Andrew D.. German Research Centre for Geosciences; Alemania. University of Minnesota; Estados UnidosFil: Miller, Louis H.. Macalester College; Estados UnidosFil: MacGregor, Kelly R.. Macalester College; Estados Unido

Incarceration history and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis

Background People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity. Findings We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40–2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28–2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94–1·65) and a 21% increase in HCV (1·21, 1·02–1·43) acquisition risk. Interpretation Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID

The cost-effectiveness of case-finding strategies for achieving hepatitis C elimination among men who have sex with men in the UK.

Modelling suggests hepatitis C virus (HCV) elimination is possible among men who have sex with men (MSM), with key screening groups including HIV-diagnosed MSM and MSM using pre-exposure prophylaxis (PrEP). Mathematical modelling was used to determine the cost-effectiveness of HCV case-finding strategies among MSM from the provider perspective, and to determine which interventions could achieve a 90% reduction in HCV incidence over 2015-2030. At baseline, we assumed symptomatic screening in HIV-negative MSM (including PrEP users) and 12-monthly screening among HIV-diagnosed MSM. Improved case-finding strategies included screening alongside HIV testing in HIV-negative MSM not using PrEP (PrEP non-users); 12/6/3-monthly screening in PrEP users; and 6-monthly screening in HIV-diagnosed MSM, with the cost-effectiveness being compared incrementally. Costs (GBP) and quality-adjusted life years (QALYs) were assessed to estimate the mean incremental cost-effectiveness ratio (ICER) with a time horizon to 2050, compared to a willingness-to-pay threshold of £20,000/QALY. From the baseline, the most incrementally cost-effective strategy is to firstly undertake: (1) 12-monthly HCV screening of PrEP users (gaining 6715 QALYs with ICER £1760/QALY), followed by (2) HCV screening among PrEP non-users alongside HIV testing (gaining 7048 QALYs with ICER £4972/QALY). Compared to the baseline, this combined strategy would cost £46.9 (95%CrI £25.3-£66.9) million and achieve the HCV elimination target in 100% of model runs. Additional screening incurs ICERs >£20,000/QALY compared to this combined strategy. In conclusion, HCV elimination can be achieved cost-effectively among UK MSM. Policymakers should consider scaling-up HCV screening in HIV-negative MSM, especially PrEP users, for achieving this target