Impact of simplified HCV diagnostic strategies on the HCV epidemic among men who have sex with men in the era of HIV oral pre-exposure prophylaxis in Taiwan: a modelling study.

INTRODUCTION: Simplified hepatitis C virus (HCV) diagnostic strategies have the potential to improve HCV diagnoses and treatment. We aimed to investigate the impact of simplified HCV diagnostic strategies on HCV incidence and its effect on HCV diagnosis and treatment among men who have sex with men (MSM) regardless of HIV status and use of HIV pre-exposure prophylaxis (PrEP) in Taiwan. METHODS: A compartmental deterministic model was developed to describe the natural history of HCV disease progression, the HCV care cascade and the HIV status and PrEP using among MSM. The model was calibrated to available data for HCV and HIV epidemiology and population demographics in Taiwan. We simulated the epidemic from 2004 and projected the impact of simplified testing strategies on the HCV epidemic among MSM over 2022-2030. RESULTS: Under the current testing approach in Taiwan, total HCV incidence would increase to 12.6 per 1000 person-years among MSM by 2030. Single-visit point-of-care RNA testing had the largest impact on reducing the number of new HCV infections over 2022-2030, with a 31.1% reduction (interquartile range: 24.9%-32.8%). By 2030, single-visit point-of-care HCV testing improved HCV diagnosis to 90.9%, HCV treatment to 87.7% and HCV cure to 81.5% among MSM living with HCV. Compared to status quo, prioritized simplified HCV testing for PrEP users and MSM living with diagnosed HIV had considerable impact on the broader HCV epidemic among MSM. A sensitivity analysis suggests that reinfection risk would have a large impact on the effectiveness of each point-of-care testing scenario. CONCLUSIONS: Simplified HCV diagnostic strategies could control the ongoing HCV epidemic and improve HCV testing and treatment among Taiwanese MSM. Single-visit point-of-care RNA testing would result in large reductions in HCV incidence and prevalence among MSM. Efficient risk-reduction strategies will need to be implemented alongside point-of-care testing to achieve HCV elimination among MSM in Taiwan.

We have reached single-visit testing, diagnosis, and treatment for hepatitis C infection, now what?

INTRODUCTION: Progress toward hepatitis C virus (HCV) elimination is impeded by low testing and treatment due to the current diagnostic pathway requiring multiple visits leading to loss to follow-up. Point-of-care testing technologies capable of detecting current HCV infection in one hour are a 'game-changer.' These tests enable diagnosis and treatment in a single visit, overcoming the barrier of multiple visits that frequently leads to loss to follow-up. Combining point-of-care HCV antibody and RNA tests should improve cost-effectiveness, patient/provider acceptability, and testing efficiency. However, implementing HCV point-of-care testing programs at scale requires multiple considerations. AREAS COVERED: This commentary explores the need for point-of-care HCV tests, diagnostic strategies to improve HCV testing, key considerations for implementing point-of-care HCV testing programs, and remaining challenges for point-of-care testing (including operator training, quality management, connectivity and reporting systems, regulatory approval processes, and the need for more efficient tests). EXPERT OPINION: It is exciting that single-visit testing, diagnosis, and treatment for HCV infection have been achieved. Innovations afforded through COVID-19 should facilitate the accelerated development of low-cost, rapid, and accurate tests to improve HCV testing. The next challenge will be to address barriers and facilitators for implementing point-of-care testing to deliver them at scale.

National Surveillance of Home-Based HIV Testing Among Australian Gay and Bisexual Men, 2018-2020: Uptake After Commercial Availability of HIV Self-Tests.

HIV self-testing allows people to collect samples and test themselves at home, addressing known barriers to facility-based testing. We aimed to measure the uptake of home HIV testing among Australian gay and bisexual men (GBM). Using national cross-sectional data from the Australian Gay Community Periodic Surveys, we assessed trends in home HIV testing among non-HIV positive GBM between 2018 and 2020. Overall, the use of home HIV testing was low, but slightly increased during 2018-2020 (from 0.3 to 0.8%, RR = 1.54, 95%CI = 1.23-1.92, p-trend < 0.001). Testing at home was more likely among non-HIV-positive GBM who were born overseas and recently arrived in Australia, at higher risk of HIV, and infrequent HIV testers. Given the greater use of home testing by men at higher risk of HIV, recent migrants and infrequent testers, all priority groups in Australia's HIV epidemic, we recommend increasing access to HIV self-testing to enhance uptake in these and other groups of GBM.

Hepatitis C virus transmission between eight high-income countries among men who have sex with men: a whole-genome analysis.

BACKGROUND: Microelimination of the hepatitis C virus (HCV) among men who have sex with men (MSM) could be complicated by continuous external introductions and the emergence of phylogenetic clusters harbouring clinically significant resistance-associated substitutions (RAS). To investigate international clustering and the prevalence and transmission of RAS, we aimed to analyse whole-genome HCV sequences from MSM with a recently acquired infection who participated in a large, international HCV treatment trial. METHODS: For this whole-genome analysis, we obtained HCV sequences from 128 MSM who had acquired HCV within the past 12 months and were participating in the REACT trial. The participants from whom sequences were obtained were recruited at 24 sites in eight countries. We inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately. We constructed time-scaled phylogenies to estimate cluster introduction dates and used a Bayesian Skygrid approach to estimate the effective population size over the past 50 years. We calculated the prevalence of RAS and the extent of RAS transmission in the study population. FINDINGS: The majority of recent HCV infections were part of international networks that arose in the late 1990s and early 2000s. Sequences obtained in the same country clustered frequently, and in 36% of subclusters since 2015 we found evidence of international transmission. European MSM were more likely than non-European MSM to be in a cluster (odds ratio 11·9 [95% CI 3·6-43·4], p<0·0001). The effective population size decreased rapidly since around 2015 in Europe. RAS associated with substantially diminished cure rates were infrequently detected and transmission of highly resistant viruses was not observed. INTERPRETATION: Despite antiviral treatment becoming widely available, international transmission of HCV among MSM has still occurred over the past 8 years, which could complicate microelimination of the virus in this population. RAS-enriched clusters and widespread RAS transmission are currently not a threat to elimination goals. These findings support an international approach for HCV microelimination among MSM. FUNDING: National Institutes of Health and Dr. C.J. Vaillant Fonds.

Barriers and facilitators to HIV and syphilis rapid diagnostic testing in antenatal care settings in low-income and middle-income countries: a systematic review.

BACKGROUND: Testing and treatment during pregnancy is a well-established and cost-effective prevention strategy, which relies largely on use of rapid diagnostic tests (RDTs). Yet, in many low-income and-middle-income countries, the uptake of RDTs is suboptimal. A qualitative meta-synthesis was conducted to identify the barriers and enablers to use of HIV and syphilis RDTs among pregnant women in low-income and middle-income countries. METHODS: This review was conducted using PRISMA guidelines. Eligible studies included peer-reviewed publications, which used qualitative methods to explore HIV and syphilis RDT in antenatal care clinics in low-income and middle-income countries. Studies focusing on perspectives of pregnant women, healthcare workers and/or stakeholders were included. We used an inductive approach informed by a modified socioecological model to synthesise the data. RESULTS: 62 manuscripts met the eligibility criteria. For pregnant women, initial acceptance of the RDT and continuation in antenatal care depends on the perception that engaging in testing will be a beneficial experience for their baby and themselves, often influenced by the provision of services that are gender-sensitive, confidential, respectful, flexible and considers their well-being into the future. Local sociocultural beliefs about pregnancy and diseases, awareness of diseases and gender roles in society also influenced RDT acceptability among pregnant women. For healthcare workers, the ability to provide high-quality RDT care required ongoing training, accurate and easy to use tests, support from supervisors and communities, sufficient resources and staffing to provide services, and reliable salary. At the stakeholder level, well-developed guidelines and health system infrastructures were imperative to the delivery of RDT in antenatal clinics. CONCLUSION: Our findings highlight clear gaps to the provision of sustainable and culturally acceptable maternal HIV and/or syphilis screening using RDTs. In addition, greater attention needs to be paid to community stakeholders in promoting the uptake of RDT in antenatal clinics. PROSPERO REGISTRATION NUMBER: CRD42018112190.

Preferences for HIV Testing Services and HIV Self-Testing Distribution Among Migrant Gay, Bisexual, and Other Men Who Have Sex With Men in Australia.

Background: In Australia, undiagnosed HIV rates are much higher among migrant gay, bisexual, or other men who have sex with men (GBMSM) than Australian-born GBMSM. HIV self-testing is a promising tool to overcome barriers to HIV testing and improve HIV testing uptake among migrant GBMSM. We compared the preferences for HIV testing services, including HIV self-testing, among migrant and Australian-born GBMSM. Methods: Preferences were assessed via two discrete choice experiments (DCEs). Participants were recruited between December 2017 and January 2018 using online and offline advertising and randomly assigned to complete one of two online DCE surveys. Migrant GBMSM were classified as being born in a country with a reciprocal healthcare agreement (RHCA) with Australia (providing free or subsided health care) or not. Latent class analysis and mixed logit models were used to explore heterogeneity in preferences. Findings: We recruited 1,606 GBMSM, including 583 migrant men of whom 419 (72%) were born in non-RHCA countries. Most participants preferred a free or cheap oral test with higher accuracy and a shorter window period to facilitate early detection of infections. Cost was more important for men born in non-RHCA countries than for men from RHCA countries or Australia. All groups preferred accessing kits through online distributers or off the shelf purchasing from pharmacies. Men born in RHCA countries least preferred accessing HIV self-testing kits from a medical clinic, while more than half of men from non-RHCA countries most preferred sourcing kits from a clinic. Sex-on-premises venues were the least preferred location to access test kits among all groups. In addition, two latent class analyses explored heterogeneity in preferences among men from non-RHCA countries and we found four latent classes for HIV testing services and two latent classes for HIVST distribution. Interpretation: Our findings emphasise the need for high-performing and low-cost HIV self-testing kits that are accessible from a variety of distribution points as a component of Australia's HIV response, especially for those who do not have access to free or subsidised health care in Australia.

Supply-side readiness to deliver HIV testing and treatment services in Indonesia: Going the last mile to eliminate mother-to-child transmission of HIV.

INTRODUCTION: Despite national efforts to integrate Prevention of Mother-to-Child Transmission (PMTCT) of HIV services into antenatal care in Indonesia, the rate of mother-to-child transmission of HIV remains the highest in the world. A range of barriers to uptake and long-term engagement in care have been identified, but far less is known about health system preparedness to deliver PMTCT of HIV services. This study explored supply-side barriers to the delivery of PMTCT services in Indonesia and whether these factors are associated with the uptake of antenatal HIV testing. MATERIALS AND METHODS: An ecological analysis was undertaken, linking data from the World Bank Quality Service and Delivery Survey (2016) with routine data from Indonesia's HIV and AIDS case surveillance system and district health profile reports (2016). Supply-side readiness scores-generated from a readiness index that measures overall structural capacity and is often used as proxy for quality of care-were adapted from the WHO Service Availability and Readiness Assessment and presented by sector and geographic area. Univariate and multivariate regression analysis was used to explore factors associated with the uptake of antenatal HIV testing in public facilities. RESULTS: In general, public facilities scored more highly in most inputs compared to private facilities. Facilities located in urban areas also scored more highly in the majority of inputs compared to ones in rural areas. Readiness scores were lowest for PMTCT services compared to Antenatal Care and HIV Care and Support services, especially for the availability of medicines such as zidovudine and nevirapine. The national composite readiness score for PMTCT was only 0.13 (based on a maximum score of 1) with a composite score of 0.21 for public facilities and 0.06 for private facilities. The multivariate analysis shows that the proportion of pregnant women tested for HIV was more likely to be greater than or equal to 10% in facilities with a higher readiness score and a higher number of trained counsellors available, and less likely in facilities located outside of Java-Bali and in facilities supporting a higher number of village midwives. DISCUSSION: Despite targeted efforts by the Indonesian government and multinational agencies, significant gaps exist in the delivery of PMTCT that compromise the standard of care delivered in Indonesia. Future strategies should focus on improving the availability of tests and treatment, especially in the private sector and in rural areas.

Sustaining success: a qualitative study of gay and bisexual men's experiences and perceptions of HIV self-testing in a randomized controlled trial.

BACKGROUND: HIV self-testing was proved as an effective tool for increasing testing frequency in gay and bisexual men at high risk of infection. Questions remain about understanding why HIVST encouraged testing and how such success can be translated to programmatic implementation. METHODS: We conducted a qualitative investigation of how FORTH participants experienced and perceived HIVST. Stratified sampling was used to recruit gay and bisexual men participating in the FORTH HIVST intervention to take part in interviews, focusing on infrequent testers and those who had received inaccurate HIVST results. RESULTS: Our analysis identified several prominent themes organized into two overarching domains from the 15 interviews: (i) aspects of HIVST contributing to HIV testing frequency, and (ii) sustaining HIVST into the future. Participants also believed that their use of HIVST in the future would depend on the test kit's reliability, particularly when compared with highly reliable clinic-based testing. CONCLUSION: HIVST increases the frequency of HIV testing among gay and bisexual men due, in part, to the practical, psychological, and social benefits it offers. To capitalize fully on these benefits, however, strategies to ensure the availability of highly reliable HIVST are required to sustain benefits beyond the confines of a structured research study.

The longer-term effects of access to HIV self-tests on HIV testing frequency in high-risk gay and bisexual men: follow-up data from a randomised controlled trial.

BACKGROUND: A wait-list randomised controlled trial in Australia (FORTH) in high-risk gay and bisexual men (GBM) showed access to free HIV self-tests (HIVSTs) doubled the frequency of HIV testing in year 1 to reach guideline recommended levels of 4 tests per year, compared to two tests per year in the standard-care arm (facility-based testing). In year 2, men in both arms had access to HIVSTs. We assessed if the effect was maintained for a further 12 months. METHODS: Participants included GBM reporting condomless anal intercourse or > 5 male partners in the past 3 months. We included men who had completed at least one survey in both year 1 and 2 and calculated the mean tests per person, based on the validated self-report and clinic records. We used Poisson regression and random effects Poisson regression models to compare the overall testing frequency by study arm, year and testing modality (HIVST/facility-based test). FINDINGS: Overall, 362 men completed at least one survey in year 1 and 343 in year 2. Among men in the intervention arm (access to HIVSTs in both years), the mean number of HIV tests in year 2 (3⋅7 overall, 2⋅3 facility-based tests, 1⋅4 HIVSTs) was lower compared to year 1 (4⋅1 overall, 1⋅7 facility-based tests, 2⋅4 HIVSTs) (RR:0⋅84, 95% CI:0⋅75-0⋅95, p=0⋅002), but higher than the standard-care arm in year 1 (2⋅0 overall, RR:1⋅71, 95% CI:1⋅48-1.97, p<0⋅001). Findings were not different when stratified by sociodemographic characteristics or recent high risk sexual history. INTERPRETATION: In year 2, fewer HIVSTs were used on average compared to year 1, but access to free HIVSTs enabled more men to maintain higher HIV testing frequency, compared with facility-based testing only. HIV self-testing should be a key component of HIV testing and prevention strategies. FUNDING: This work was supported by grant 568971 from the National Health and Medical Research Council of Australia.

Sofosbuvir/velpatasvir for 12 vs. 6 weeks for the treatment of recently acquired hepatitis C infection.

BACKGROUND & AIMS: Shortened duration therapy for acute and recent HCV infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral regimens; however, large randomised studies are lacking. METHODS: REACT was an NIH-funded multicentre international, open-label, randomised, phase IV non-inferiority trial examining the efficacy of short course (6-week) vs. standard course (12-week) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection ≤12 months). Randomisation occurred at week 6. The primary endpoint was sustained virological response 12 weeks after treatment end (SVR12) in the intention-to treat (ITT) population. A total of 250 participants were due to be enrolled, but on advice of the data safety and monitoring board the study was halted early. RESULTS: The primary analysis population consisted of 188 randomised participants at termination of study enrolment; short arm (n = 93), standard arm (n = 95). Ninety-seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4-89.0) in the short arm and 86/95, 90.5% (95% CI 82.7-95.6) in the standard arm. The difference between the arms was -8.8 (95% CI -18.6 to 1.0). In modified ITT analysis, wherein non-virological reasons for failure were excluded (death, reinfection, loss to follow-up), SVR12 was 76/85, 89.4% (95% CI 80.8-95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0-99.7; difference -8.3%, p = 0.025). CONCLUSIONS: In this randomised study in recent HCV infection, a 6-week course of sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12-week therapy. LAY SUMMARY: In this randomised trial, 188 people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were 9 cases of relapse after treatment with the short course and 2 following the standard course. A shortened course of 6-week therapy for hepatitis C infection appeared to be less effective than a standard 12-week course in people with recently acquired hepatitis C infection. CLINICALTRIALS. GOV IDENTIFIER: NCT02625909.

The costs of scaling up HIV and syphilis testing in low- and middle-income countries: a systematic review.

Around two-thirds of all new HIV infections and 90% of syphilis cases occur in low- and middle-income countries (LMICs). Testing is a key strategy for the prevention and treatment of HIV and syphilis. Decision-makers in LMICs face considerable uncertainties about the costs of scaling up HIV and syphilis testing. This paper synthesizes economic evidence on the costs of scaling up HIV and syphilis testing interventions in LMICs and evidence on how costs change with the scale of delivery. We systematically searched multiple databases (Medline, Econlit, Embase, EMCARE, CINAHL, Global Health and the NHS Economic Evaluation Database) for peer-reviewed studies examining the costs of scaling up HIV and syphilis testing in LMICs. Thirty-five eligible studies were identified from 4869 unique citations. Most studies were conducted in Sub-Saharan Africa (N = 17) and most explored the costs of rapid HIV in facilities targeted the general population (N = 19). Only two studies focused on syphilis testing. Seventeen studies were cost analyses, 17 were cost-effectiveness analyses and 1 was cost-benefit analysis of HIV or syphilis testing. Most studies took a modelling approach (N = 25) and assumed costs increased linearly with scale. Ten studies examined cost efficiencies associated with scale, most reporting short-run economies of scale. Important drivers of the costs of scaling up included testing uptake and the price of test kits. The 'true' cost of scaling up testing is likely to be masked by the use of short-term decision frameworks, linear unit-cost projections (i.e. multiplying an average cost by a factor reflecting activity at a larger scale) and availability of health system capacity and infrastructure to supervise and support scale up. Cost data need to be routinely collected alongside other monitoring indicators as HIV and syphilis testing continues to be scaled up in LMICs.

Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs.

BACKGROUND: The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT). METHODS: Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models. RESULTS: Seventy-three percent of the population at risk of reinfection (n = 177; median age, 48 years; 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median, 1.8 years; range, 0.2-2.8 years). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% confidence interval [CI], 1.6-6.3) overall and 17.9/100 person-years (95% CI, 5.8-55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection. CONCLUSIONS: These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination. CLINICAL TRIALS REGISTRATION: NCT02336139 and NCT02498015.

Evaluation of the Aptima HCV Quant Dx Assay for Hepatitis C Virus RNA Detection from Fingerstick Capillary Dried Blood Spot and Venepuncture-Collected Samples.

BACKGROUND: Simplified diagnostic strategies are needed increase hepatitis C virus (HCV) testing to determine active infection and link people into treatment. Collection methods such as dried blood spots (DBS) have advantages over standard phlebotomy, especially within marginalized populations. METHODS: We evaluated the diagnostic performance of the Aptima HCV Quant assay for the quantification and detection of HCV RNA from paired DBS and venepuncture samples. Specimens were collected from participants enrolled in an Australian observational study. We compared HCV RNA detection from DBS against venepuncture samples (gold standard). RESULTS: One hundred sixty-four participants had paired samples and HCV RNA was detected in 45 (27% [95% confidence interval, 21%-35%]) by the Aptima assay in venepuncture samples. Sensitivity of the Aptima assay for HCV RNA quantification from DBS (≥10 IU/mL in plasma) was 100% and specificity was 100%. Sensitivity for HCV RNA detection from DBS was 95.6% and specificity was 94.1%. A small bias in plasma over DBS was observed with good agreement (R2 = 0.96). CONCLUSIONS: The Aptima HCV Quant assay detects active infection from DBS samples with acceptable diagnostic performance and is clinically comparable to plasma. These data will strengthen the case for the registration of a DBS kit insert claim, enabling future clinical utility.

Novel Hepatitic C Virus (HCV) Diagnosis and Treatment Delivery Systems: Facilitating HCV Elimination by Thinking Outside the Clinic.

The World Health Organization has set a goal to eliminate hepatitis C virus (HCV) infection as public health threat by 2030. Although the advent of highly effective and tolerable direct-acting antiviral therapy has paved the way for HCV elimination, most people with HCV infection remain undiagnosed and untreated globally, with striking disparities between high-income and low- to middle-income countries. Novel decentralized and cost-effective "test-and-treat" strategies are critically needed to identify the millions of people unaware of their status and link them to treatment.

Evaluation of Commercially Available Viral Transport Medium (VTM) for SARS-CoV-2 Inactivation and Use in Point-of-Care (POC) Testing.

Critical to facilitating SARS-CoV-2 point-of-care (POC) testing is assurance that viruses present in specimens are inactivated onsite prior to processing. Here, we conducted experiments to determine the virucidal activity of commercially available Viral Transport Mediums (VTMs) to inactivate SARS-CoV-2. Independent testing methods for viral inactivation testing were applied, including a previously described World Health Organization (WHO) protocol, in addition to a buffer exchange method where the virus is physically separated from the VTM post exposure. The latter method enables sensitive detection of viral viability at higher viral titre when incubated with VTM. We demonstrate that VTM formulations, Primestore® Molecular Transport Medium (MTM) and COPAN eNAT™ completely inactivate high-titre SARS-CoV-2 virus (>1 × 107 copies/mL) and are compatible with POC processing. Furthermore, full viral inactivation was rapidly achieved in as little as 2 min of VTM exposure. We conclude that adding certain VTM formulations as a first step post specimen collection will render SARS-CoV-2 non-infectious for transport, or for further in-field POC molecular testing using rapid turnaround GeneXpert platforms or equivalent.

Impact of an Open Access Nationwide Treatment Model on Hepatitis C Virus Antiviral Drug Resistance.

Direct acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment, but drug resistance could undermine proposed global elimination targets. Real-world studies are needed to inform the impact of widespread DAA treatment on antiviral resistance in the community. The prevalence and range of posttreatment resistance-associated substitutions (RASs) was determined in Australian patients with open access to DAAs through a wide range of prescribers. NS3, NS5A, and NS5B regions were amplified by polymerase chain reaction and analyzed by population sequencing. Clinically relevant RASs were identified using online databases (ReCALL and Geno2Pheno[hcv]). Of 572 samples, 60% were from genotype 3 and 27% from genotype 1a. Ninety-two percent of people failed a DAA regimen containing an NS5A inhibitor, including 10% with a pangenotype regimen. NS5A RASs were detected in 72% of people with genotype 1 and 80% with genotype 3. For genotype 1, there was a range of RASs across the NS5A region, while for genotype 3, the Y93H RAS predominated (72%). The prevalence of NS3 RASs was higher in people exposed to an NS3 inhibitor (35% vs. 3.9%; P < 0.0001). NS5B resistance was rare, with a single case of sofosbuvir resistance. Multiclass drug resistance was found in 33% of people exposed to both NS3 and NS5A inhibitors. Conclusion: The high prevalence of NS5A RASs among people failing DAA therapy reinforces the importance of specific retreatment regimens, ideally guided by resistance testing. The impact of multiclass drug resistance on retreatment in people exposed to both NS3 and NS5A inhibitors needs to be assessed in real-world studies. Surveillance for increasing antiviral resistance during treatment scale-up is essential to maintain the efficacy of current DAA regimens.

Modeling based response guided therapy in subjects with recent hepatitis C infection.

BACKGROUND & AIMS: Mathematical modeling of viral kinetics has been shown to identify patients with chronic hepatitis C virus (HCV) infection who could be cured with a shorter duration of direct-acting antiviral (DAA) treatment. However, modeling therapy duration has yet to be evaluated in recently infected individuals. The aim of this study was to retrospectively examine whether modeling can predict outcomes of six-week sofosbuvir (SOF) and weight-based ribavirin (R) therapy in individuals with recent HCV infection. METHODS: Modeling was used to estimate viral host parameters and to predict time to cure for 12 adults with recent HCV infection (<12 months of infection) who received six weeks of treatment with SOF + R. RESULTS: Modeling results yielded a 100% negative predictive value for SOF + R treatment response in nine participants and suggested that a median of 13 [interquartile range: 8-16] weeks of therapy would be required for these patients to achieve cure. Modeling predicted cure after 5 weeks of therapy in the only modeled participant who achieved a sustained virological response. However, cure was also predicted for two participants who relapsed following treatment. CONCLUSIONS: The modeling results confirm that longer than 6 weeks of SOF + R is needed to reach cure in individuals with recent HCV infection. Prospective real-time modeling under current potent DAA regimens is needed to validate the potential of response-guided therapy in the management of recent HCV infection.

Elbasvir and grazoprevir for hepatitis C virus genotype 1 infection in people with recent injecting drug use (DARLO-C): An open-label, single-arm, phase 4, multicentre trial.

BACKGROUND AND AIMS: Direct-acting antiviral therapy for hepatitis C virus (HCV) is effective, but few prospective studies among people with ongoing injecting drug use exist. This study evaluated the efficacy of elbasvir/grazoprevir in people with HCV genotype 1/4 (G1/4) infection and recent injecting drug use. An exploratory aim evaluated the feasibility of fingerstick point-of-care HCV RNA testing prior to and following treatment. METHODS: DARLO-C (http://clinicaltrials.gov: NCT02940691) is an open-label phase 4 trial. Participants were recruited between May 2017 and March 2018 from two drug treatment clinics, two hospital clinics, and one community clinic in Australia. Inclusion criteria included recent injection drug use (previous 6 months) and HCV G1/4 infection. Exclusion criteria included prior HCV treatment and decompensated liver disease. Participants received elbasvir/grazoprevir once-daily for 12 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (SVR). Fingerstick whole-blood samples were tested using the Xpert HCV Viral Load Fingerstick (Xpert HCV VL Fingerstick) assay and compared to the Aptima HCV Quant Dx Assay on plasma samples. RESULTS: Of a planned 150 participants, 32 were enrolled due to slower than anticipated recruitment [median age 46 years, 10 (31%) female, 29 (91%) G1a]. Eighteen (56%) were receiving opioid agonist therapy and 29 (91%) injected in the previous month. Twenty-six (81%) of 32 completed treatment (lost to follow-up, n = 5; incarceration, n = 1). There were no virological failures. Twenty-four (75%, 95% CI 59%-91%) of 32 achieved SVR. Two participants who completed treatment did not have SVR (loss to follow-up, n = 1; refused test, n = 1). Among paired samples (n = 36), sensitivity of the Xpert HCV VL Fingerstick assay for HCV RNA detection was 100.0% (95% CI 75.3%-100.0%) and specificity was 95.7% (95% CI 78.1%-99.9%). CONCLUSION: Elbasvir/grazoprevir is effective among people with HCV G1 with recent injecting drug use. Implementation of point-of-care HCV RNA testing was feasible, but the high error rate requires investigation.

Time to Detection of Hepatitis C Virus Infection With the Xpert HCV Viral Load Fingerstick Point-of-Care Assay: Facilitating a More Rapid Time to Diagnosis.

BACKGROUND: Xpert HCV Viral Load Fingerstick assay (Xpert HCV VL FS) is a point-of-care test quantifying HCV RNA in <1 hour, enabling same-visit diagnosis and treatment. METHODS: This study evaluated time to HCV RNA detection using the Xpert HCV VL FS assay. Fingerstick whole-blood samples were collected from participants in an observational cohort in Australia. RESULTS: In May 2018-2019, 1468 participants were enrolled, 1426 had Xpert HCV VL FS testing performed, and 1386 had a valid result. HCV RNA was detected in 23% (325/1386). Among people with undetectable HCV RNA (n = 1061), median time to result was 57 minutes. Among people with detectable HCV RNA (n = 325), median time to HCV RNA detection was 32 minutes and 80% (261/325) had a detectable HCV RNA result in ≤40 minutes. Median time to HCV RNA detection was dependent on HCV RNA level. CONCLUSIONS: A quicker HCV diagnosis could be achieved by monitoring the time when HCV RNA is first detected with the Xpert HCV VL FS test, rather than HCV RNA quantification, although the current platform does not allow for this. These findings could facilitate new strategies to reduce waiting times for an HCV diagnosis and improve linkage to treatment.

Evaluation of a hepatitis C virus core antigen assay from venepuncture and dried blood spot collected samples: A cohort study.

The global scale-up of hepatitis C virus (HCV) diagnosis requires simplified and affordable HCV diagnostic pathways. This study evaluated the sensitivity and specificity of the HCV Architect core antigen (HCVcAg) assay for detection of active HCV infection in plasma and capillary whole blood dried blood spots (DBS) compared with HCV RNA testing in plasma (Abbott RealTime HCV Viral Load). Samples were collected from participants in an observational cohort enrolled at three sites in Australia (two-drug treatment and alcohol clinics and one homelessness service). Of 205 participants, 200 had results across all samples and assay types and 186 were included in this analysis (14 participants receiving HCV therapy were excluded). HCV RNA was detected in 29% of participants ([95% CI: 22.6-36.1], 54 of 186). The sensitivity of HCVcAg for detection of active HCV infection in plasma was 98.1% (95% CI: 90-100) and 100% (95% CI: 93-100) when compared to HCV RNA thresholds of ≥12 and ≥1000 IU/mL, respectively. The sensitivity of the HCVcAg assay for detection of active HCV infection in DBS was 90.7% (95% CI: 80-97) and 92.5% (95% CI: 82-98) when compared to HCV RNA thresholds of ≥12 and ≥1000 IU/mL, respectively. The specificity of HCV core antigen for detection of active infection was 100% (95% CI: 97-100) for all samples and RNA thresholds. These data indicate that the detection of HCVcAg is a useful tool for determining active HCV infection; to facilitate enhanced testing, linkage to care and treatment particularly when testing plasma samples are collected by venepuncture.