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AbstractIntroductionThe introduction of drugs targeting the virus replication cycle has revolutionized treatment of chronic hepatitis C virus. These drugs, called direct‐acting antivirals, have brought about extremely high rates of virological cure and have increased the number of patients who can receive treatment due to the lack of absolute contraindications. A combination of different classes of direct‐acting antivirals is the current standard of care. Although treatment administration and monitoring has been simplified in recent years, it is still relatively complex and mostly in the hands of specialists. Several factors must be assessed before starting treatment to maximize efficacy and minimize side effects of treatment. In this review, we describe the factors that impact on the efficacy and safety of antiviral treatment for hepatitis C and provide clear recommendations for clinicians prescribing direct‐acting antivirals.MethodsWe reviewed literature to define best practice, based on factors associated with treatment efficacy and safety data to recommend treatment options, baseline and on‐treatment assessments. The review included searches in PubMed, and the abstracts presented at the International Liver Congress TM and The Liver Meeting TM between January 2013 and September 2017.ResultsClinical features that must be assessed before starting treatment include virological factors, such as hepatitis C virus genotype, HIV and hepatitis B coinfection and host factors, such as concomitant medications, liver disease stage and renal function.ConclusionsPatients who start antiviral treatment for chronic hepatitis C require a thorough clinical evaluation. There is a need for assessing factors that impact on the treatment schedule and duration or affect the pharmacokinetics of direct‐acting antivirals.

Introduction: A lack of access to hepatitis C virus (HCV) diagnostics is a significant barrier to achieving the World Health Organization 2030 global elimination goal. HCV core antigen (HCVcAg) quantification and dried blood spot (DBS) are appealing alternatives to conventional HCV serology and nucleic acid testing (NAT) for resource‐constraint settings, particularly in difficult‐to‐reach populations. We assessed the accuracy of serum and DBS HCVcAg testing in people who inject drugs in Tanzania using HCV NAT as a reference.Method: Between May and July 2015, consecutive HCV‐seropositive patients enrolled in the local opioid substitution treatment centre were invited to participate in the study. All had HCV RNA detection (Roche Molecular Systems, Pleasanton, CA, USA), genotyping (NS5B gene phylogenetic analysis) and HCVcAg on blood samples and DBS (Architect assay; Abbott Diagnostics, Chicago, IL, USA).Results: Out of 153 HCV‐seropositive individuals, 65 (42.5%) and 15 (9.8%) were co‐infected with HIV (41 (63%) were on anti‐retroviral therapy (ARVs)) and hepatitis B respectively. In total, 116 were viraemic, median viral load of 5.7 (Interquartile range (IQR); 4.0–6.3) log iU/ml (75 (68.2%) were genotype 1a, 35 (31.8%) genotype 4a). The median alanine transaminase (ALT) (iU/l), aspartate transaminase (AST) (iU/l) and gamma‐glutamyl transferase (GGT) (iU/l) were 35 (IQR; 23–51), 46 (32–57) and 69 (35–151) respectively. For the quantification of HCV RNA, serum HCVcAg had a sensitivity at 99.1% and a specificity at 94.1%, with an area under the receiver operating curve (AUROC) at 0.99 (95% CI 0.98–1.00). DBS HCVcAg had a sensitivity of 76.1% and a specificity of 97.3%, with an AUROC of 0.87 (95% CI 0.83–0.92). HCVcAg performance did not differ by HIV co‐infection or HCV genotype.Conclusions: Our study suggests that HCVcAg testing in serum is an excellent alternative to HCV polymerase chain reaction in Africa. Although HCVcAg detection and quantification in DBS has a reduced sensitivity, its specificity and accuracy are good and it could therefore be used for scaling up HCV testing and care in resource‐limited African settings.

IntroductionTransmission of Hepatitis C virus (HCV) among HIV‐positive men who have sex with men (MSM) in the United Kingdom is ongoing. We explore associations between self‐reported sexual behaviours and drug use with cumulative HCV prevalence, as well as new HCV diagnosis.MethodsASTRA is a cross‐sectional questionnaire study including 2,248 HIV‐diagnosed MSM under care in the United Kingdom during 2011–2012. Socio‐demographic, lifestyle, HIV‐related and sexual behaviour data were collected during the study. One thousand seven hundred and fifty two (≥70%) of the MSM who consented to linkage of ASTRA and clinical information (prior to and post questionnaire) were included. Cumulative prevalence of HCV was defined as any positive anti‐HCV or HCV‐RNA test result at any point prior to questionnaire completion. We excluded 536 participants with clinical records only after questionnaire completion. Among the remaining 1,216 MSM, we describe associations of self‐reported sexual behaviours and recreational drug use in the three months prior to ASTRA with cumulative HCV prevalence, using modified Poisson regression with robust error variances. New HCV was defined as any positive anti‐HCV or HCV‐RNA after questionnaire completion. We excluded 591 MSM who reported ever having a HCV diagnosis at questionnaire, any positive HCV result prior to questionnaire or did not have any HCV tests after the questionnaire. Among the remaining 1,195 MSM, we describe occurrence of new HCV diagnosis during follow‐up according to self‐reported sexual behaviours and recreational drug use three months prior to questionnaire (Fisher's exact test).ResultsCumulative HCV prevalence among MSM prior to ASTRA was 13.3% (95% CI 11.5–15.4). Clinic‐ and age‐adjusted prevalence ratios (95% CI) for cumulative HCV prevalence were 4.6 (3.1–6.7) for methamphetamine, 6.5 (3.5–12.1) for injection drugs, 2.3 (1.6–3.4) for gamma hydroxybutyrate (GHB), 1.6 (1.3–2.0) for nitrites, 1.7 (1.5–2.0) for all condom‐less sex (CLS), 2.1 (1.7–2.5) for CLS‐HIV‐seroconcordant, 1.3 (0.9–1.9) for CLS‐HIV‐serodiscordant, 2.0 (1.6–2.5) for group sex, 1.5 (1.2–1.9) for more than 10 new sexual partners in the past year. Among 1,195 MSM with 2.2 years [IQR 1.5–2.4] median follow‐up, there were 7 new HCV cases during 2,033 person‐years at risk. Incidence was 3.5 per 1,000 person‐years (95% CI 1.6–7.2). New HCV was recorded in 1.3% MSM who used methamphetamine versus 0.5% MSM who did not (p=0.385); 3.7% MSM who injected recreational drugs versus 0.5% MSM who did not (p=0.148); 2.9% MSM who used GHB versus 0.4% MSM who did not (p=0.003); 1.5% MSM who used nitrites versus 0.2% MSM who did not (p=0.019); 1.1% MSM having CLS versus 0.3% MSM who did not (p=0.084); 1.7% MSM having CLS‐HIV‐serodiscordant versus 0.4% MSM who did not (p=0.069); 0.9% MSM who had CLS‐HIV‐seroconcordant versus 0.5% MSM who did not (p=0.318); 0.8% MSM who had group sex versus 0.5% MSM who did not (p=0.463); and 1.6% MSM with =10 new sexual partners in the previous year versus 0.2% MSM with no or up to 9 new partners (p=0.015).ConclusionsSelf‐reported recent use of recreational and injection drugs, condom‐less sex and multiple new sexual partners are associated with pre‐existing HCV infection and, with the exception of injection drugs, appear to be predictive of new HCV co‐infection among HIV‐diagnosed MSM.

AbstractIntroductionExploration of sexual and drug use behaviours following treatment for recent hepatitis C virus (HCV) is limited. This analysis modelled behavioural trajectories following treatment for recent HCV and assessed reinfection.MethodsParticipants treated for recent HCV in an international trial (enrolled 2017–2019) were followed at 3‐monthly intervals for up to 2 years to assess longitudinal behaviours. Population‐averaged changes were assessed using generalized estimating equations. Distinct behavioural trajectories were identified using group‐based trajectory modelling. HCV reinfection incidence was calculated using person‐years (PY) of observation.ResultsDuring the follow‐up of 212 participants (84% gay and bisexual men [GBM]; 69% HIV; 26% current injecting drug use [IDU]), behavioural trajectories for IDU and stimulant use (past month) did not change. However, population‐averaged decreases in the likelihood of daily IDU (adjusted odds ratio [AOR] 0.83; 95% CI 0.72, 0.95) and opioid use (AOR 0.84; 95% CI 0.75, 0.93) were observed. Among GBM, behavioural trajectories for chemsex did not change. Population‐averaged decreases in condomless anal intercourse with casual male partners (CAI‐CMP) (AOR 0.95; 95% CI 0.90, 0.99) and group‐sex (AOR 0.86; 95% CI 0.80, 0.93) were observed, but masked distinct trajectories. While a proportion had a decreased probability of CAI‐CMP (23%) and group‐sex (59%) post‐treatment, a substantial proportion retained a high probability of these behaviours. High HCV reinfection incidence was observed for the sustained high probability IDU (33.0/100 PY; 95% CI 17.7, 61.3) and chemsex (23.3/100 PY; 95% CI 14.5, 37.5) trajectories.ConclusionsLimited sexual and drug use behavioural change was observed following treatment for recent HCV, supporting access to surveillance and (re)treatment.