Long-term trends in human body size track regional variation in subsistence transitions and growth acceleration linked to dairying.

Evidence for a reduction in stature between Mesolithic foragers and Neolithic farmers has been interpreted as reflective of declines in health, however, our current understanding of this trend fails to account for the complexity of cultural and dietary transitions or the possible causes of phenotypic change. The agricultural transition was extended in primary centers of domestication and abrupt in regions characterized by demic diffusion. In regions such as Northern Europe where foreign domesticates were difficult to establish, there is strong evidence for natural selection for lactase persistence in relation to dairying. We employ broad-scale analyses of diachronic variation in stature and body mass in the Levant, Europe, the Nile Valley, South Asia, and China, to test three hypotheses about the timing of subsistence shifts and human body size, that: 1) the adoption of agriculture led to a decrease in stature, 2) there were different trajectories in regions of in situ domestication or cultural diffusion of agriculture; and 3) increases in stature and body mass are observed in regions with evidence for selection for lactase persistence. Our results demonstrate that 1) decreases in stature preceded the origins of agriculture in some regions; 2) the Levant and China, regions of in situ domestication of species and an extended period of mixed foraging and agricultural subsistence, had stable stature and body mass over time; and 3) stature and body mass increases in Central and Northern Europe coincide with the timing of selective sweeps for lactase persistence, providing support for the "Lactase Growth Hypothesis."

B-cell characteristics define HCV reinfection outcome.

BACKGROUND & AIMS: In individuals highly exposed to HCV, reinfection is common, suggesting that natural development of sterilising immunity is difficult. In those that are reinfected, some will develop a persistent infection, while a small proportion repeatedly clear the virus, suggesting natural protection is possible. The aim of this study was to characterise immune responses associated with rapid natural clearance of HCV reinfection. METHODS: Broad neutralising antibodies (nAbs) and Envelope 2 (E2)-specific memory B cell (MBC) responses were examined longitudinally in 15 individuals with varied reinfection outcomes. RESULTS: Broad nAb responses were associated with MBC recall, but not with clearance of reinfection. Strong evidence of antigen imprinting was found, and the B-cell receptor repertoire showed a high level of clonality with ongoing somatic hypermutation of many clones over subsequent reinfection events. Single-cell transcriptomic analyses showed that cleared reinfections featured an activated transcriptomic profile in HCV-specific B cells that rapidly expanded upon reinfection. CONCLUSIONS: MBC quality, but not necessarily breadth of nAb responses, is important for protection against antigenically diverse variants, which is encouraging for HCV vaccine development. IMPACT AND IMPLICATIONS: HCV continues to have a major health burden globally. Limitations in the health infrastructure for diagnosis and treatment, as well as high rates of reinfection, indicate that a vaccine that can protect against chronic HCV infection will greatly complement current efforts to eliminate HCV-related disease. With alternative approaches to testing vaccines, such as controlled human inoculation trials under consideration, we desperately need to identify the correlates of immune protection. In this study, in a small but rare cohort of high-risk injecting drug users who were reinfected multiple times, breadth of neutralisation was not associated with ultimate clearance of the reinfection event. Alternatively, characteristics of the HCV-specific B-cell response associated with B-cell proliferation were. This study indicates that humoral responses are important for protection and suggests that for genetically very diverse viruses, such as HCV, it may be beneficial to look beyond just antibodies as correlates of protection.

Characterization of antibody-dependent cellular phagocytosis in patients infected with hepatitis C virus with different clinical outcomes.

Early neutralizing antibodies against hepatitis C virus (HCV) and CD8 + T cell effector responses can lead to viral clearance. However, these functions alone are not sufficient to protect patients against HCV infection, thus undefined additional antiviral immune mechanisms are required. In recent years, Fc-receptor-dependent antibody effector functions, particularly, antibody-dependent cellular phagocytosis (ADCP) were shown to offer immune protection against several RNA viruses. However, its development and clinical role in patients with HCV infection remain unknown. In this study, we found that patients with chronic GT1a or GT3a HCV infection had significantly higher concentrations of anti-envelope 2 (E2) antibodies, predominantly IgG1 subclass, than patients that cleared the viruses while the latter had antibodies with higher affinities. 97% of the patients with HCV had measurable ADCP of whom patients with chronic disease showed significantly higher ADCP than those who naturally cleared the virus. Epitope mapping studies showed that patients with antibodies that target antigenic domains on the HCV E2 protein that are known to associate with neutralization function are also strongly associated with ADCP, suggesting antibodies with overlapping/dual functions. Correlation studies showed that ADCP significantly correlated with plasma anti-E2 antibody levels and neutralization function regardless of clinical outcome and genotype of infecting virus, while a significant correlation between ADCP and affinity was only evident in patients that cleared the virus. These results suggest ADCP was mostly driven by antibody titer in patients with chronic disease while maintained in clearers due to the quality (affinity) of their anti-E2 antibodies despite having lower antibody titers.

Prison-based interventions are key to achieving HCV elimination among people who inject drugs in New South Wales, Australia: A modelling study.

BACKGROUND & AIMS: People who inject drugs (PWID) experience high incarceration rates which are associated with increased hepatitis C virus (HCV) transmission risk. We assess the importance of prison-based interventions for achieving HCV elimination among PWID in New South Wales (NSW), Australia. METHODS: A model of incarceration and HCV transmission among PWID was calibrated in a Bayesian framework to epidemiological and incarceration data from NSW, incorporating elevated HCV acquisition risk among recently released PWID. We projected the contribution of differences in transmission risk during/following incarceration to HCV transmission over 2020-2029. We estimated the past and potential future impact of prison-based opioid agonist therapy (OAT; ~33% coverage) and HCV treatment (1500 treatments in 2019 with 32.9%-83.3% among PWID) on HCV transmission. We estimated the time until HCV incidence reduces by 80% (WHO elimination target) compared to 2016 levels with or without prison-based interventions. RESULTS: Over 2020-2029, incarceration will contribute 23.0% (17.9-30.5) of new HCV infections. If prison-based interventions had not been implemented since 2010, HCV incidence in 2020 would have been 29.7% (95% credibility interval: 22.4-36.1) higher. If current prison and community HCV treatment rates continue, there is an 98.8% probability that elimination targets will be achieved by 2030, with this decreasing to 10.1% without current prison-based interventions. CONCLUSIONS: Existing prison-based interventions in NSW are critical components of strategies to reduce HCV incidence among PWID. Prison-based interventions are likely to be pivotal for achieving HCV elimination targets among PWID by 2030.

COVID-19 Testing in a Weekly Cohort Study of Gay and Bisexual Men: The Impact of Health-Seeking Behaviors and Social Connection.

Gay, bisexual, and other men who have sex with men (GBM) have developed community norms for regular HIV/STI testing. We investigated factors associated with self-reported COVID-19 testing in response to reported COVID-19 cases and public health restrictions. Participants responded to weekly cohort surveys between 10th May 2021 and 27th September 2021. We used the Andersen-Gill extensions to the Cox proportional hazards model for multivariable survival data to predict factors influencing COVID-19 testing. Mean age of the 942 study participants was 45.6 years (SD: 13.9). In multivariable analysis, GBM were more likely to report testing during periods of high COVID-19 caseload in their state of residence; if they were younger; university educated; close contact of someone with COVID-19; or reported coping with COVID-19 poorly. COVID-19 testing was higher among men who: were more socially engaged with other GBM; had a higher proportion of friends willing to vaccinate against COVID-19; and were willing to contact sexual partners for contact tracing. Social connection with other gay men was associated with COVID-19 testing, similar to what has been observed throughout the HIV epidemic, making community networks a potential focus for the promotion of COVID-19 safe practices.

Prevalence and incidence of emergency department presentations and hospital separations with injecting-related infections in a longitudinal cohort of people who inject drugs.

People who inject drugs are at risk of acute bacterial and fungal injecting-related infections. There is evidence that incidence of hospitalizations for injecting-related infections are increasing in several countries, but little is known at an individual level. We aimed to examine injecting-related infections in a linked longitudinal cohort of people who inject drugs in Melbourne, Australia. A retrospective descriptive analysis was conducted to estimate the prevalence and incidence of injecting-related infections using administrative emergency department and hospital separation datasets linked to the SuperMIX cohort, from 2008 to 2018. Over the study period, 33% (95%CI: 31-36%) of participants presented to emergency department with any injecting-related infections and 27% (95%CI: 25-30%) were admitted to hospital. Of 1,044 emergency department presentations and 740 hospital separations, skin and soft tissue infections were most common, 88% and 76%, respectively. From 2008 to 2018, there was a substantial increase in emergency department presentations and hospital separations with any injecting-related infections, 48 to 135 per 1,000 person-years, and 18 to 102 per 1,000 person-years, respectively. The results emphasize that injecting-related infections are increasing, and that new models of care are needed to help prevent and facilitate early detection of superficial infection to avoid potentially life-threatening severe infections.

How to have sex in a pandemic: the development of strategies to prevent COVID-19 transmission in sexual encounters among gay and bisexual men in Australia.

Although many studies reported on decreases in sexual partner numbers among gay and bisexual-identifying men in the early period of the COVID-19 pandemic, few studies have explored COVID-19 risk-reduction strategies. Drawing on free-text responses in an online survey (from April to July 2020), we describe the ways in which men sought to minimise the risk of COVID-19 in sexual encounters. Partner selection was an important strategy, in particular, restricting sex to men they already knew. Accounts also indicate how participants assessed risk from potential sex partners based on symptoms, residential location, recent travel, work role, and number of other sexual contacts. Less common were in situ practices, such as avoiding kissing. Participants' responses provide insight into creative community-based responses in the early months of the pandemic, some of which have resonances with early responses to HIV. Findings are discussed in relation to the concepts of 'lay epidemiology' and 'counterpublic health'. In particular, we examine how risks and health are experienced and valued in relation to local knowledges, meanings, and practices; and how practices emerge in response to dominant public health discourses that produce an idealised public based on (hetero)normative assumptions.

Reasons for not Using HIV Pre-Exposure Prophylaxis (PrEP) among Gay and Bisexual Men in Australia: Mixed-Methods Analyses from a National, Online, Observational Study.

Although approximately 31,000 Australian gay and bisexual men (GBM) are eligible for HIV pre-exposure prophylaxis (PrEP), only 18,500 people currently use it, indicating a need to investigate why GBM do not use it. This article uses data from a national, online, observational study. It adopts a mixed-methods analysis to responses to survey questions asking about reasons Australian GBM were not using PrEP in 2018, according to their level of HIV risk as delineated by the Australian PrEP prescribing guidelines at the time. Participants responded to check-box questions and had the option to respond to a qualitative free-text question. Results showed that just over one-fifth of men were at higher risk of HIV acquisition. Compared to lower-risk men, higher-risk men were more likely to indicate PrEP was too expensive and more likely to cite embarrassment asking for it. Reasons for not using PrEP included a lack of personal relevance, poor accessibility or knowledge, concerns about PrEP's inability to protect against STIs, potential side effects, and a preference for condoms. We conclude that health promotion more effectively targeting GBM who may benefit the most from PrEP may be valuable.

Mothers Who Use Drugs: Closing the Gaps in Harm Reduction Response Amidst the Dual Epidemics of Overdose and Violence in a Canadian Urban Setting.

Objectives. To identify key gaps in overdose prevention interventions for mothers who use drugs and the paradoxical impact of institutional practices that can increase overdose risk in the context of punitive drug policies and a toxic drug supply. Methods. Semistructured interviews were conducted with 40 women accessing 2 women-only, low-barrier supervised consumption sites in Greater Vancouver, British Columbia, Canada, between 2017 and 2019. Our analysis drew on intersectional understandings of structural, everyday, and symbolic violence. Results. Participants' substance use and overdose risk (e.g., injecting alone) was shaped by fear of institutional and partner scrutiny and loss (or feared loss) of child custody or reunification. Findings indicate that punitive policies and institutional practices that frame women who use drugs as unfit parents continue to negatively shape the lives of women, most significantly among Indigenous participants. Conclusions. Nonpunitive policies, including access to safe, nontoxic drug supplies, are critical first steps to decreasing women's overdose risk alongside gender-specific and culturally informed harm-reduction responses, including community-based, peer-led initiatives to maintain parent-child relationships. (Am J Public Health. 2022;112(S2):S191-S198. https://doi.org/10.2105/AJPH.2022.306776).

Increase in Depression and Anxiety Among Australian Gay and Bisexual Men During COVID-19 Restrictions: Findings from a Prospective Online Cohort Study.

We examined depression and anxiety prior to and during COVID-19 restrictions in Australian gay and bisexual men (GBM). In an online cohort, a COVID-19-focused survey was conducted in April 2020. During 2019 and in April 2020, 664 GBM completed the Patient Health Questionnaire (PHQ-9, measuring depression) and Generalized Anxiety Disorder Assessment (GAD-7, measuring anxiety). Increased depression and anxiety were defined as a ≥ 5 point increase on the respective scales. Mean PHQ-9 and GAD-7 scores increased between 2019 and 2020 (PHQ-9: from 5.11 in 2019 to 6.55 in 2020; GAD-7: from 3.80 in 2019 to 4.95 in 2020). The proportion of participants with moderate-severe depression (PHQ-9 ≥ 10) increased from 18.8% (n = 125) to 25.5% (n = 169), while the proportion of participants with moderate-severe anxiety (GAD-7 ≥ 10) increased from 12.7% (n = 84) to 17.3% (n = 115). Almost one-quarter of participants (n = 158, 23.8%) had increased depression; in these men, mean PHQ-9 increased from 2.49 in 2019 to 11.65 in 2020 (p < 0.001). One-in-five (20.6%) participants (n = 137) had increased anxiety; among these men, mean GAD-7 increased from 2.05 in 2019 to 10.22 in 2020 (p < 0.001). Increases were associated with concerns about job security, reduction in social and sexual connections and opportunities, and being personally concerned about COVID-19 itself. COVID-19 appeared to have a sudden and pronounced impact on depression and anxiety in Australian GBM, with a significant minority showing sharp increases. Ongoing monitoring is required to determine longer-term impacts and GBM need access to appropriate and sensitive supports both during and after the COVID-19 pandemic.

Uptake of COVID-19 vaccination among people who inject drugs.

BACKGROUND: People who inject drugs (PWID) may be at elevated risk of adverse outcomes from SARS-CoV-2 infection; however, data on COVID-19 vaccine uptake among PWID are scarce. This study aimed to determine COVID-19 vaccine uptake among PWID, identify factors associated with sub-optimal uptake, and compare uptake to the general population. METHODS: The Australian Needle Syringe Program Survey is an annual sentinel surveillance project, comprising a self-completed questionnaire and provision of a dried blood sample for HIV and HCV testing. In 2021, respondents provided information on their COVID-19 vaccination status. Multivariate logistic regression models identified correlates of vaccine uptake. RESULTS: Among 1166 respondents, 49% had been vaccinated and in most states and territories, vaccine uptake was significantly lower than among the general population. Independent predictors of vaccine uptake were longer duration of vaccine eligibility (AOR 3.42, 95% CI 2.65, 4.41); prior SARS-CoV-2 diagnostic testing (AOR 2.90, 95% CI 2.22, 3.79); injection of opioids (AOR 1.91, 95% CI 1.20, 3.05); and current opioid agonist therapy (AOR 1.70, 95% CI 1.23, 2.33). Women (AOR 0.70, 95% CI 0.54, 0.92) and those who reported daily or more frequent injection (AOR 0.75, 95% CI 0.57, 1.00) were significantly less likely to be vaccinated. CONCLUSIONS: In most Australian states and territories, uptake of COVID-19 vaccine among PWID lagged uptake among the general population. Increased efforts are required to ensure PWID have equitable access to vaccination. Vaccination programmes within harm reduction services and via outreach, coupled with increased support for peers to act as vaccine champions, are likely to reduce barriers and improve COVID-19 vaccine uptake in this population.

Changes in Sexual Behaviour Following PrEP Initiation Among Australian Gay and Bisexual Men in Relationships: Results from a Prospective Observational Study.

Few studies have examined changes in sexual behaviour following HIV pre-exposure prophylaxis (PrEP) initiation among gay, bisexual and other men who have sex with men (GBM) in relationships. In a national, online, prospective study of GBM in Australia, we compared sexual behaviours prior to and after PrEP initiation among HIV-negative and unknown-HIV-status men (recruited 2014-2017) not taking PrEP at baseline and who completed at least one six-monthly follow-up by July 2018. Among men in relationships who did not initiate PrEP (n = 339), we compared their most recent survey to their prior one, while among men in relationships who initiated PrEP (n = 81), we compared follow-ups before and after PrEP initiation. Among the 81 PrEP-initiators who were in a relationship both before and after initiation, the proportion reporting their regular partner was on PrEP increased from 8.3 to 44.4% (p < 0.001) and the proportion reporting receptive CLAIC increased from 27.2 to 44.4% (p = 0.009). Overall, men who initiated PrEP were more likely to be in a relationship with a partner on PrEP, and it appeared they started PrEP around the same time. Receptive CLAIC also became more common.

Estimating the number of new hepatitis C infections in Australia in 2015, prior to the scale-up of direct-acting antiviral treatment.

BACKGROUND AND AIM: The recent downward revision of the estimated number of people living with chronic hepatitis C in Australia means that the annual number of new hepatitis C infections should also be revised. We aimed to estimate the annual number of new hepatitis C infections among people who inject drugs (PWID) in Australia in 2015, prior to the introduction of direct-acting antiviral (DAA) treatment for hepatitis C, as an updated baseline measure for assessing the impact of DAAs on hepatitis C incidence over the next 10 years. METHODS: A systematic review identified articles estimating hepatitis C incidence rates among PWID between 2002 and 2015. Reported incidence rates were adjusted to account for unrepresentative needle and syringe program (NSP) coverage among study participants compared with PWID overall. The total number of PWID in Australia and the hepatitis C RNA prevalence among PWID were taken from published estimates. The annual number of new infections was estimated by multiplying the pooled NSP coverage-adjusted incidence rate by the number of susceptible PWID in 2015. RESULTS: Five studies were included, with unadjusted incidence rates ranging from 7.6 to 12.8 per 100 person-years. The overall pooled incidence rate (after adjusting for NSP coverage) was 9.9 per 100 person-years (95% confidence interval: 8.3-11.8). This led to an estimate of 4126 (range 2499-6405) new hepatitis C infections in 2015. CONCLUSIONS: Our updated estimate provides an important baseline for evaluating the impact of hepatitis C elimination efforts and can be used to validate outcomes of future modeling studies.

Hoots and harm reduction: a qualitative study identifying gaps in overdose prevention among women who smoke drugs.

BACKGROUND: Smoking or inhaling illicit drugs can lead to a variety of negative health outcomes, including overdose. However, most overdose prevention interventions, such as supervised consumption services (SCS), prohibit inhalation. In addition, women are underrepresented at SCS and are disproportionately impacted by socio-structural violence. This study examines women's experiences smoking illicit drugs during an overdose epidemic, including their utilization of a women-only supervised inhalation site. METHODS: Qualitative research methods included on-site ethnographic observation and semi-structured interviews with 32 participants purposively recruited from the women-only site. Data were coded and analyzed using NVivo 12 and thematic analysis was informed by gendered and socio-structural understandings of violence. RESULTS: Participants had preferences for smoking drugs and these were shaped by their limited income, inability to inject, and perceptions of overdose risk. Participants expressed the need for services that attend to women's specific experiences of gendered, race-based, and structural violence faced within and outside mixed-gender social service settings. Results indicate a need for sanctioned spaces that recognize polysubstance use and drug smoking, accommodated by the women-only SCS. The smoking environment further fostered a sociability where participants could engage in perceived harm reduction through sharing drugs with other women/those in need and were able to respond in the event of an overdose. CONCLUSIONS: Findings demonstrate the ways in which gendered social and structural environments shape women's daily experiences using drugs and the need for culturally appropriate interventions that recognize diverse modes of consumption while attending to overdose and violence. Women-only smoking spaces can provide temporary reprieve from some socio-structural harms and build collective capacity to practice harm reduction strategies, including overdose prevention. Women-specific SCS with attention to polysubstance use are needed as well as continued efforts to address the socio-structural harms experienced by women who smoke illicit drugs.

HIV incidence and associated risk factors in female spouses of men who inject drugs in Pakistan.

INTRODUCTION: Female sexual partners of men who inject drugs (MWID) living with HIV are at risk of HIV transmission. HIV prevalence estimates among non-drug using female sex partners of MWID are scarce, with no studies documenting HIV incidence. We investigated HIV prevalence and incidence among female spouses of MWID registered at Nai Zindagi Trust (NZT), Pakistan, between 2012 and 2019. METHODS: NZT registration and service provision data for female spouses who participated in HIV testing and counselling calculated HIV prevalence and incidence using the person years (PY) method. Cox proportional hazards models identified factors associated with incident infection. RESULTS: Overall HIV prevalence among female spouses of MWID was 8.5%. Among 3478 HIV-negative female spouses, 109 incident infections were observed, yielding an incidence rate of 1.5/100PY (95% CI 1.2-1.8). Independent predictors of incident infection were registration in Punjab province (AHR 1.73 95% CI 1.13-2.68, p = 0.012) and 1-5 years of education (AHR 1.89 95% CI 1.22-2.93, p = 0.004). Knowledge of HIV at registration was protective against infection (AHR 0.51, 95% CI 0.26-0.99, p = 0.047), along with a MWID spouse who had initiated antiretroviral therapy (ART) (AHR 0.25, 95% CI 0.16-0.38, p < 0.001), while incident infection was inversely associated with number of children (≥ 5 children AHR 0.44 95% CI 0.22-0.88, p = 0.022). CONCLUSIONS: Additional efforts are needed to reduce HIV transmission among female spouses of MWID, including targeted provision of HIV education and access to HIV screening. Interventions that target MWID are also required, including evidence-based drug treatment and access to ART, including support to maximize adherence. Finally, consideration should be given to making HIV pre-exposure prophylaxis available to female spouses at high risk of HIV transmission, particularly young women and those whose husbands are not receiving, or have difficulty adhering to, ART.

Working with Aboriginal young people in sexual health research: a peer research methodology in remote Australia.

In a context of ongoing colonization and dispossession in Australia, many Aboriginal people live with experiences of health research that is done "on" rather than "with" or "by" them. Recognizing the agency of young people and contributing to Aboriginal self-determination and community control of research, we used a peer research methodology involving Aboriginal young people as researchers, advisors, and participants in a qualitative sexual health study in one remote setting in the Northern Territory, Australia. We document the methodology, while critically reflecting on its benefits and limitations as a decolonizing method. Findings confirm the importance of enabling Aboriginal young people to play a central role in research with other young people about their own sexual health. Future priorities include developing more enduring forms of coinvestigation with Aboriginal young people beyond data collection during single studies, and support for young researchers to gain formal qualifications to enhance future employability.

Qualitative Findings on the Impact of COVID-19 Restrictions on Australian Gay and Bisexual Men: Community Belonging and Mental Well-being.

COVID-19 may threaten the already poor mental health outcomes of Australian gay and bisexual men and cut ties to important social/sexual networks and community. Qualitative research into the experiences of gay and bisexual men during COVID-19 regulations is currently sparse. We report on 489 responses to a qualitative free-text question asking Australian gay and bisexual men about the impacts of COVID-19 during April 2020. Issues pertinent to gay and bisexual men include lost ties to gay and bisexual social/sexual communities, spaces, and activities, which can reduce a sense of belonging to important sexual identity spaces, as well as significant mental well-being vulnerabilities. Reminiscing the collective response to HIV/AIDS, findings reinforce the value of gay and bisexual community organizations, spaces, and networks as supports for gay and bisexual men and emphasize the need for delivering mental health services.

A Systematic Review of Interventions Used to Increase Blood Donor Compliance with Deferral Criteria.

BACKGROUND AND OBJECTIVES: Pre-donation screening of potential blood donors is critical for ensuring the safety of the donor blood supply, and donor deferral as a result of risk factors is practised worldwide. This systematic review was conducted in the context of an expert review convened by the Australian Red Cross Lifeblood in 2013 to consider Lifeblood's injecting drug use (IDU)-related policies and aimed to identify studies assessing interventions to improve compliance with deferral criteria in blood donation settings. MATERIALS AND METHODS: MEDLINE/PubMed, OVID Medline, OVID Embase, LILACS, and the Cochrane Library (CENTRAL and DARE) databases were searched for studies conducted within blood donation settings that examined interventions to increase blood donor compliance with deferral criteria. Observational and experimental studies from all geographical areas were considered. RESULTS: Ten studies were identified that tested at least one intervention to improve blood donor compliance with deferral criteria, including computerized interviews or questionnaires, direct and indirect oral questioning, educational materials, and a combination of a tickbox questionnaire and a personal donor interview. High-quality evidence from a single study was provided for the effectiveness of a computerized interview in improving detection of HIV risk behaviour. Low-quality evidence for the effectiveness of computerized interviews was provided by 3 additional studies. Two studies reported a moderate effect of direct questioning in increasing donor deferral, but the quality of the evidence was low. CONCLUSION: This review identified several interventions to improve donor compliance that have been tested in blood donation settings and provided evidence for the effectiveness of computerized interviews in improving detection of risk factors.

Sex Discrepancies in the Protective Effect of Opioid Agonist Therapy on Incident Hepatitis C Infection.

BACKGROUND: While opioid agonist therapy (OAT) reduces the risk of hepatitis C virus (HCV) acquisition among people who inject drugs (PWID), protective effects may be attenuated in females. We used pooled data from an international collaboration of prospective cohorts to assess sex disparities in HCV incidence among PWID exposed to OAT. METHODS: Independent predictors of HCV infection were identified using Cox regression models with random effects after accounting for the clustering effect of study sites. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are presented in sex-specific analyses. RESULTS: Among 701 participants exposed to OAT, HCV incidence was 16.5/100 person-years of observation (PYO) (95% CI, 13.1-20.7) in females and 7.6/100 PYO (95% CI, 6.0-9.5) in males (female:male adjusted HR [aHR], 1.80 [95% CI, 1.37-2.22]; P < .001). Factors associated with HCV acquisition among females exposed to OAT included nonwhite race (aHR, 1.79 [95% CI, 1.25-2.56]; P = .001), unstable housing (aHR, 4.00 [95% CI, 3.62-4.41]; P < .001), daily or more frequent injection (aHR, 1.45 [95% CI, 1.01-2.08]; P = .042), and receptive syringe sharing (aHR, 1.43 [95% CI, 1.33-1.53]; P < .001). CONCLUSIONS: Female PWID exposed to OAT are twice as likely as their male counterparts to acquire HCV. While there is a need for better understanding of sex differences in immune function and opioid pharmacokinetic and pharmacodynamic parameters, structural and behavioral interventions that target women are required to bolster the efficacy of OAT in preventing HCV transmission.

B cell immunodominance in primary hepatitis C virus infection.

BACKGROUND & AIMS: Neutralising antibodies (NAbs) play a key role in clearance of HCV. NAbs have been isolated and mapped to several domains on the HCV envelope proteins. However, the immunodominance of these epitopes in HCV infection remains unknown, hindering efforts to elicit optimal epitope-specific responses. Furthermore, it remains unclear which epitope-specific responses are associated with broad NAb (bNAb) activity in primary HCV infection. The aim of this study was to define B cell immunodominance in primary HCV, and its implications on neutralisation breadth and clearance. METHODS: Using samples from 168 patients with primary HCV infection, the antibody responses targeted 2 immunodominant domains, termed domains B and C. Genotype 1 and 3 infections were associated with responses targeted towards different bNAb domains. RESULTS: No epitopes were uniquely targeted by clearers compared to those who developed chronic infection. Samples with bNAb activity were enriched for multi-specific responses directed towards the epitopes antigenic region 3, antigenic region 4, and domain D, and did not target non-neutralising domains. CONCLUSIONS: This study outlines for the first time a clear NAb immunodominance profile in primary HCV infection, and indicates that it is influenced by the infecting virus. It also highlights the need for a vaccination strategy to induce multi-specific responses that do not target non-neutralising domains. LAY SUMMARY: Neutralising antibodies will likely form a key component of a protective hepatitis C virus vaccine. In this work we characterise the predominant neutralising and non-neutralising antibody (epitope) targets in acute hepatitis C virus infection. We have defined the natural hierarchy of epitope immunodominance, and demonstrated that viral genotype can impact on this hierarchy. Our findings highlight key epitopes that are associated with broadly neutralising antibodies, and the deleterious impact of mounting a response towards some of these domains on neutralising breadth. These findings should guide future efforts to design immunogens aimed at generating neutralising antibodies with a vaccine candidate.