Lisa Maher

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)

Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection.

High hepatitis C incidence in new injecting drug users: a policy failure?

Objective: Evidence of ongoing hepatitis C (HCV) transmission among injecting drug users (IDUs) suggests a need for a better understanding of seroconversion characteristics among new IDUs and other vulnerable subgroups. This study aimed to determine incidence of HCV and associated risk factors among new IDUs in Sydney.

Women on the edge of crime: Crack cocaine and the changing contexts of street-level sex work in New York City

In this paper, we attempt to examine, engender and contextualize the theses that (i) “womens emancipation escalates [womens] crime and violence” and (ii) “womens drug use escalates [womens] crime and violence”, by drawing on ongoing ethnographic fieldwork in relation to women crack smokers and the changing contexts of street-level sex work in New York City. The paper attempts to illustrate how the position of women crack smokers can only be understood by locating their lives, their illicit drug use and their income-generating activities within the context of a specific set of localized socio-economic and cultural developments. We suggest that observations from our research refute the theses that women are becoming more criminal and/or violent in the context of either their consumption of crack cocaine or their alleged “emancipation”.

Risk behaviors and antibody hepatitis B and C prevalence among injecting drug users in south‐western Sydney, Australia

Background and Aim:  Hepatitis C virus (HCV) infection is now the leading notifiable disease in Australia. The current study aimed to determine the prevalence of HCV and hepatitis B virus (HBV) infection and associated risk behaviors among injecting drug users (IDUs) screened in south‐western Sydney as part of a multisite prospective cohort study.

Global burden of HIV, viral hepatitis, and tuberculosis in prisoners and detainees

The prison setting presents not only challenges, but also opportunities, for the prevention and treatment of HIV, viral hepatitis, and tuberculosis. We did a comprehensive literature search of data published between 2005 and 2015 to understand the global epidemiology of HIV, hepatitis C virus (HCV), hepatitis B virus (HBV), and tuberculosis in prisoners. We further modelled the contribution of imprisonment and the potential impact of prevention interventions on HIV transmission in this population. Of the estimated 10·2 million people incarcerated worldwide on any given day in 2014, we estimated that 3·8% have HIV (389 000 living with HIV), 15·1% have HCV (1 546 500), 4·8% have chronic HBV (491 500), and 2·8% have active tuberculosis (286 000). The few studies on incidence suggest that intraprison transmission is generally low, except for large-scale outbreaks. Our model indicates that decreasing the incarceration rate in people who inject drugs and providing opioid agonist therapy could reduce the burden of HIV in this population. The prevalence of HIV, HCV, HBV, and tuberculosis is higher in prison populations than in the general population, mainly because of the criminalisation of drug use and the detention of people who use drugs. The most effective way of controlling these infections in prisoners and the broader community is to reduce the incarceration of people who inject drugs.

Uptake of hepatitis C treatment among people who inject drugs attending Needle and Syringe Programs in Australia, 1999–2011

The majority of new and existing cases of hepatitis C virus (HCV) infection occur among people who inject drugs (PWID). Despite safe and efficacious HCV antiviral therapy, uptake remains low in this population. This study examined trends in HCV treatment uptake among a large national sample of PWID attending Australian Needle and Syringe Programs between 1999 and 2011. Annual cross‐sectional sero‐surveys conducted among PWID since 1995 involve completion of a self‐administered questionnaire and provision of a dried blood spot for HCV antibody testing. Multivariate logistic regression identified variables independently associated with HCV treatment uptake among 9478 participants with both self‐reported and serologically confirmed prior HCV infection. Between 1999 and 2011, the proportion currently receiving treatment increased from 1.1% to 2.1% (P < 0.001), while the proportion having ever received treatment increased from 3.4% to 8.6% (P < 0.001). Men were significantly more likely than women to have undertaken HCV treatment (P = 0.002). Among men, independent predictors of HCV treatment uptake were homosexual identity and older age; among women, independent predictors included homosexual identity and an incarceration history. Despite increases in HCV treatment among Australian PWID between 1999 and 2011, uptake remains low. Strategies are required to increase the proportion of PWID assessed and treated for HCV infection to address the increasing burden of disease. Specific approaches that target women may also be warranted. Continued surveillance of HCV treatment uptake among PWID will be important to monitor the roll‐out of simple, safe and more effective HCV treatments expected to be available in the future.

Young Women Engaged in Sex Work in Phnom Penh, Cambodia, Have High Incidence of HIV and Sexually Transmitted Infections, and Amphetamine-Type Stimulant Use: New Challenges to HIV Prevention and Risk

Objectives: To estimate prevalence and incidence of HIV and sexually transmitted infections (STI) and associated risk factors among young women working as sex workers (SWs) in Phnom Penh, Cambodia. Methods: A prospective study of young (<29 years) women working as SWs in brothels, entertainment establishments, and freelance. Sociodemographics, sexual risk, and use of amphetamine-type stimulants (ATS) (“yama” and “crystal”) were assessed by self-report. HIV and STI (Chlamydia trachomatis and Neisseria gonorrhoeae) testing were conducted on blood and urine specimens, respectively. Results: Baseline prevalences of HIV, C. trachomatis, and N. gonorrhoeae were 23%, 11.5%, and 7.8%, respectively. HIV incidence was 3.6 per 100 person-years (95% confidence interval [CI], 1.2%–11.1%); STI incidence was 21.2 per 100 person-years (95% CI, 12.6%–35.8%). At baseline, 26.5% reported recent ATS use. HIV infection was associated with freelance SW (adjusted odds ratio, 5.85; 95% CI, 1.59–21.58) and younger age of first sex (≤15 years; adjusted odds ratio, 3.06; 95% CI, 1.01–8.46). Incident STI was associated with duration (per year) of SW (adjusted hazard ratio, 1.1; 95% CI, 1.1–1.2) and recent yama use (adjusted hazard ratio, 3.9; 95% CI, 1.5–10.3). Conclusions: HIV and STI infection rates were high among SWs working in various settings; freelancers had highest risk. ATS use was associated with incident STI. Venue of sex work and drug prevention should be considered in prevention programs.

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.

The impact of needle and syringe programs on HIV and HCV transmissions in injecting drug users in Australia: a model-based analysis.

Objectives:We aim to estimate how changes in sterile syringe distribution through needle-syringe programs (NSPs) may affect HIV and hepatitis C virus (HCV) incidence among injecting drug users (IDUs) in Australia. Methods:We develop a novel mathematical model of HIV and HCV transmission among IDUs who share syringes. It is calibrated using biological and Australian epidemiological and behavioral data. Assuming NSP syringe distribution affects the number of times each syringe is used before disposal, we use the model to estimate the relationship between incidence and syringe distribution. Results:HIV is effectively controlled through NSP distribution of sterile syringes {with the effective reproduction ratio below 1 [0.66 median, interquartile range (0.63-0.70)] under current syringe distribution}. In contrast, HCV incidence is expected to remain high and its control is not feasible in the foreseeable future. The proportion of injections that are shared and the number of times each syringe is used before disposal are the driving factors of HCV incidence. The frequency in which each syringe is used can potentially be influenced by changes in syringe distribution. We estimate that if syringe distribution or coverage doubled, then annual incidence is likely to reduce by 50%. However, if it was decreased to one third of the current level, then ∼3 times the incidence could be expected. Conclusions:This research highlights the large benefits of NSPs, puts forward a quantitative relationship between incidence and syringe distribution, and indicates that increased coverage could result in significant reductions in viral transmissions among IDUs.