Rachel Sacks-Davis

Hepatitis C treatment for injection drug users: a review of the available evidence

Globally, approximately 90% of new hepatitis C infections are attributed to injection drug use, but there is a continuing reluctance to treat injection drug users (IDUs). There is evidence that a sizeable proportion of IDUs who begin hepatitis C treatment achieve a sustained virological response (SVR). In chronic hepatitis C treatment trials, the SVR rate among IDUs appears to be comparable to rates among non-IDUs; in trials prescribing pegylated interferon plus ribavirin, the median rate of SVR among IDUs was 54.3% (range, 18.1%-94.1%), compared with 54%-63% in the large treatment trials. Few trials of acute hepatitis C treatment report on outcomes in IDUs; however, among these trials, the SVR among IDUs was 68.5% (n=89), compared with 81.5% among non-IDUs (n=65). Additional studies are required to determine the optimal circumstances for treatment (e.g., enrollment in drug treatment, the requirement of a period of abstinence from injection drug use, or the establishment of multidisciplinary treatment programs).

The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection.

Although 20%‐40% of persons with acute hepatitis C virus (HCV) infection demonstrate spontaneous clearance, the time course and factors associated with clearance remain poorly understood. We investigated the time to spontaneous clearance and predictors among participants with acute HCV using Cox proportional hazards analyses. Data for this analysis were drawn from an international collaboration of nine prospective cohorts evaluating outcomes after acute HCV infection. Among 632 participants with acute HCV, 35% were female, 82% were Caucasian, 49% had interleukin‐28 (IL28)B CC genotype (rs12979860), 96% had injected drugs ever, 47% were infected with HCV genotype 1, and 7% had human immunodeficiency virus (HIV) coinfection. Twenty‐eight percent were HCV antibody negative/RNA positive at the time of acute HCV detection (early acute HCV). During follow‐up, spontaneous clearance occurred in 173 of 632, and at 1 year after infection, 25% (95% confidence interval [CI]: 21, 29) had cleared virus. Among those with clearance, the median time to clearance was 16.5 weeks (IQR: 10.5, 33.4), with 34%, 67%, and 83% demonstrating clearance at 3, 6, and 12 months. Adjusting for age, factors independently associated with time to spontaneous clearance included female sex (adjusted hazards ratio [AHR]: 2.16; 95% CI: 1.48, 3.18), IL28B CC genotype (versus CT/TT; AHR, 2.26; 95% CI: 1.52, 3.34), and HCV genotype 1 (versus non‐genotype 1; AHR: 1.56; 95% CI: 1.06, 2.30). The effect of IL28B genotype and HCV genotype on spontaneous clearance was greater among females, compared to males. Conclusions: Female sex, favorable IL28B genotype, and HCV genotype 1 are independent predictors of spontaneous clearance. Further research is required to elucidate the observed sex‐based differences in HCV control. (Hepatology 2014;58:109–120)

A systematic examination of the use of Online social networking sites for sexual health promotion

BackgroundIn recent years social networking sites (SNSs) have grown rapidly in popularity. The popularity of these sites, along with their interactive functions, offer a novel environment in which to deliver health promotion messages. The aim of this paper is to examine the extent to which SNSs are currently being used for sexual health promotion and describe the breadth of these activities.MethodsWe conducted a systematic search of published scientific literature, electronic sources (general and scientific search engines, blogs) and SNSs (Facebook, MySpace) to identify existing sexual health promotion activities using SNSs. Health promotion activities were eligible for inclusion if they related to sexual health or behaviour, utilised one or more SNSs, and involved some element of health promotion. Information regarding the source and type of health promotion activity, target population and site activity were extracted.Results178 sexual health promotion activities met the inclusion criteria and were included in the review; only one activity was identified through a traditional systematic search of the published scientific literature. Activities most commonly used one SNS, were conducted by not-for-profit organisations, targeted young people and involved information delivery. Facebook was the most commonly used SNS (used by 71% of all health promotion activities identified), followed by MySpace and Twitter. Seventy nine percent of activities on MySpace were considered inactive as there had been no online posts within the past month, compared to 22% of activities using Facebook and 14% of activities using Twitter. The number of end-users and posts in the last seven days varied greatly between health promotion activities.ConclusionsSNSs are being used for sexual health promotion, although the extent to which they are utilised varies greatly, and the vast majority of activities are unreported in the scientific literature. Future studies should examine the key factors for success among those activities attracting a large and active user base, and how success might be measured, in order to guide the development of future health promotion activities in this emerging setting.

The impact of injecting networks on hepatitis C transmission and treatment in people who inject drugs

With the development of new highly efficacious direct‐acting antiviral (DAA) treatments for hepatitis C virus (HCV), the concept of treatment as prevention is gaining credence. To date, the majority of mathematical models assume perfect mixing, with injectors having equal contact with all other injectors. This article explores how using a networks‐based approach to treat people who inject drugs (PWID) with DAAs affects HCV prevalence. Using observational data, we parameterized an exponential random graph model containing 524 nodes. We simulated transmission of HCV through this network using a discrete time, stochastic transmission model. The effect of five treatment strategies on the prevalence of HCV was investigated; two of these strategies were (1) treat randomly selected nodes and (2) “treat your friends,” where an individual is chosen at random for treatment and all their infected neighbors are treated. As treatment coverage increases, HCV prevalence at 10 years reduces for both the high‐ and low‐efficacy treatment. Within each set of parameters, the treat your friends strategy performed better than the random strategy being most marked for higher‐efficacy treatment. For example, over 10 years of treating 25 per 1,000 PWID, the prevalence drops from 50% to 40% for the random strategy and to 33% for the treat your friends strategy (6.5% difference; 95% confidence interval: 5.1‐8.1). Conclusion: Treat your friends is a feasible means of utilizing network strategies to improve treatment efficiency. In an era of highly efficacious and highly tolerable treatment, such an approach will benefit not just the individual, but also the community more broadly by reducing the prevalence of HCV among PWID. (Hepatology 2014;60:1860–1869)

Patterns of hepatitis C virus RNA levels during acute infection: the InC3 study.

Background Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV) infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection. Methods Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study). Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels≤120 days) were categorised by a priori-defined patterns of HCV RNA levels: i) spontaneous clearance, ii) partial viral control with persistence (≥1 log IU/mL decline in HCV RNA levels following peak) and iii) viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak). Factors associated with HCV RNA patterns were assessed using multinomial logistic regression. Results Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%), partial viral control with persistence (27%), and viral plateau with persistence (41%). HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P=0.018). In the two groups with persistence, Interferon lambda 3 (IFNL3) CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02). In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83). Conclusions Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex is associated with ultimate spontaneous clearance.

High Rates of Hepatitis C Virus Reinfection and Spontaneous Clearance of Reinfection in People Who Inject Drugs: A Prospective Cohort Study

Hepatitis C virus reinfection and spontaneous clearance of reinfection were examined in a highly characterised cohort of 188 people who inject drugs over a five-year period. Nine confirmed reinfections and 17 possible reinfections were identified (confirmed reinfections were those genetically distinct from the previous infection and possible reinfections were used to define instances where genetic differences between infections could not be assessed due to lack of availability of hepatitis C virus sequence data). The incidence of confirmed reinfection was 28.8 per 100 person-years (PY), 95%CI: 15.0-55.4; the combined incidence of confirmed and possible reinfection was 24.6 per 100 PY (95%CI: 16.8-36.1). The hazard of hepatitis C reinfection was approximately double that of primary hepatitis C infection; it did not reach statistical significance in confirmed reinfections alone (hazard ratio [HR]: 2.45, 95%CI: 0.87-6.86, p=0.089), but did in confirmed and possible hepatitis C reinfections combined (HR: 1.93, 95%CI: 1.01-3.69, p=0.047) and after adjustment for the number of recent injecting partners and duration of injecting. In multivariable analysis, shorter duration of injection (HR: 0.91; 95%CI: 0.83-0.98; p=0.019) and multiple recent injecting partners (HR: 3.12; 95%CI: 1.08-9.00, p=0.035) were independent predictors of possible and confirmed reinfection. Time to spontaneous clearance was shorter in confirmed reinfection (HR: 5.34, 95%CI: 1.67-17.03, p=0.005) and confirmed and possible reinfection (HR: 3.10, 95%CI: 1.10-8.76, p-value=0.033) than primary infection. Nonetheless, 50% of confirmed reinfections and 41% of confirmed or possible reinfections did not spontaneously clear. Conclusions: Hepatitis C reinfection and spontaneous clearance of hepatitis C reinfection were observed at high rates, suggesting partial acquired natural immunity to hepatitis C virus. Public health campaigns about the risks of hepatitis C reinfection are required.

Eradication of hepatitis C infection: The importance of targeting people who inject drugs

Hepatitis C virus (HCV) affects ~170 million people worldwide and causes significant morbidity and mortality.1 In high-income countries, people who inject drugs (PWID) are at greatest risk of HCV infection.2 Until recently HCV eradication seemed unlikely, but recent advances in HCV treatment and improved understanding of the effectiveness of harm-reduction intervention effectiveness give reason for optimism. Current HCV treatments can cure ~75% of patients and new drugs will further improve effectiveness (over 90% cure) and improve tolerability.3 If HCV treatment can be delivered effectively to those at highest risk of onward transmission, significant reductions in future HCV cases are possible. The feasibility of disease eradication must be assessed on both scientific criteria (e.g., epidemiological susceptibility, effective and practical intervention available, and demonstrated feasibility of elimination) and political criteria (e.g., burden of disease, cost of intervention).4 With effective, curative treatment now available, HCV meets these criteria.

Modelling antiviral treatment to prevent hepatitis C infection among people who inject drugs in Victoria, Australia.

Objectives: To develop a mathematical model to project the potential impact of hepatitis C virus (HCV) treatment on HCV infection prevalence among people who inject drugs (PWID).

Hepatitis C Virus Phylogenetic Clustering Is Associated with the Social-Injecting Network in a Cohort of People Who Inject Drugs

It is hypothesized that social networks facilitate transmission of the hepatitis C virus (HCV). We tested for association between HCV phylogeny and reported injecting relationships using longitudinal data from a social network design study. People who inject drugs were recruited from street drug markets in Melbourne, Australia. Interviews and blood tests took place three monthly (during 2005–2008), with participants asked to nominate up to five injecting partners at each interview. The HCV core region of individual isolates was then sequenced and phylogenetic trees were constructed. Genetic clusters were identified using bootstrapping (cut-off: 70%). An adjusted Jaccard similarity coefficient was used to measure the association between the reported injecting relationships and relationships defined by clustering in the phylogenetic analysis (statistical significance assessed using the quadratic assignment procedure). 402 participants consented to participate; 244 HCV infections were observed in 238 individuals. 26 genetic clusters were identified, with 2–7 infections per cluster. Newly acquired infection (AOR = 2.03, 95% CI: 1.04–3.96, p = 0.037, and HCV genotype 3 (vs. genotype 1, AOR = 2.72, 95% CI: 1.48–4.99) were independent predictors of being in a cluster. 54% of participants whose infections were part of a cluster in the phylogenetic analysis reported injecting with at least one other participant in that cluster during the study. Overall, 16% of participants who were infected at study entry and 40% of participants with newly acquired infections had molecular evidence of related infections with at least one injecting partner. Likely transmission clusters identified in phylogenetic analysis correlated with reported injecting relationships (adjusted Jaccard coefficient: 0.300; p<0.001). This is the first study to show that HCV phylogeny is associated with the injecting network, highlighting the importance of the injecting network in HCV transmission.

The More You Look, the More You Find: Effects of Hepatitis C Virus Testing Interval on Reinfection Incidence and Clearance and Implications for Future Vaccine Study Design

INTRODUCTION Studies have explored whether spontaneous clearance of hepatitis C virus (HCV) infection decreases the likelihood of reinfection or increases the probability of clearance. This analysis investigates whether the conflicting findings from these studies could be due to differences in frequency of HCV RNA testing. METHODS A model simulated the dynamics of HCV reinfection and clearance among a cohort of injection drug users. For different reinfection incidence and clearance rates, the model evaluated the accuracy of epidemiological studies that used different HCV testing frequencies. RESULTS Experimental estimates for the reinfection incidence and clearance probability will be accurate (<20% error) if the testing interval is less than the reinfection clearance duration. Otherwise, experimental estimates can greatly underestimate the real values (≤66% error if reinfection duration is 1 month and the testing interval is 3 months). Uncertainty in experimental estimates also increases at lower reinfection incidences, whereas for lower clearance probabilities the uncertainty in the estimated clearance probability increases but estimated reinfection incidence decreases. DISCUSSION Differences in HCV testing interval could account for most between-study variability in the estimated probability of clearing reinfections and is likely to have biased reinfection incidence estimates. Our findings suggest that a high reinfection clearance probability (>75%) is consistent with data.