Patterns of drug use among people who inject drugs: A global systematic review and meta-analysis.

BACKGROUND: A better understanding of global patterns of drug use among people who inject drugs can inform interventions to reduce harms related to different use profiles. This review aimed to comprehensively present the geographical variation in drug consumption patterns among this population. METHODS: Systematic searches of peer reviewed (PsycINFO, Medline, Embase) and grey literature published from 2008-2022 were conducted. Data on recent (past year) and lifetime drug use among people who inject drugs were included. Data were extracted on use of heroin, amphetamines, cocaine, benzodiazepines, cannabis, alcohol, and tobacco; where possible, estimates were disaggregated by route of administration (injecting, non-injecting, smoking). National estimates were generated and, where possible, regional, and global estimates were derived through meta-analysis. RESULTS: Of 40,427 studies screened, 394 were included from 81 countries. Globally, an estimated 78.1 % (95 %CI:70.2-84.2) and 71.8 % (65.7-77.2) of people who inject drugs had recently used (via any route) and injected heroin, while an estimated 52.8 % (47.0-59.0) and 19.8 % (13.8-26.5) had recently used and injected amphetamines, respectively. Over 90 % reported recent tobacco use (93.5 % [90.8-95.3]) and recent alcohol use was 59.1 % (52.6-65.6). In Australasia recent heroin use was lowest (49.4 % [46.8-52.1]) while recent amphetamine injecting (64.0 % [60.8-67.1]) and recent use of cannabis (72.3 % [69.9-74.6]) were higher than in all other regions. Recent heroin use (86.1 % [78.3-91.4]) and non-injecting amphetamine use (43.3 % [38.4-48.3]) were highest in East and Southeast Asia. Recent amphetamine use (75.8 % [72.7-78.8]) and injecting heroin use (84.8 % (81.4-87.8) were highest in North America while non-injecting heroin use was highest in Western Europe (45.0 % [41.3-48.7]). CONCLUSION: There is considerable variation in types of drugs and routes of administration used among people who inject drugs. This variation needs to be considered in national and global treatment and harm reduction interventions to target the specific behaviours and harms associated with these regional profiles of use.

Vaccination coverage among people who inject drugs: A systematic review.

BACKGROUND: People who inject drugs may be at excess risk of acquiring vaccine-preventable diseases and negative associated health outcomes, but experience barriers to vaccination. We aimed to determine vaccination coverage among people who inject drugs globally. METHODOLOGY: We conducted systematic searches of the peer-reviewed and grey literature, date limited from January 2008 to August 2023, focusing on diseases for which people who inject drugs are at elevated risk for and for which an adult vaccination dose is recommended (COVID-19, hepatitis A, hepatitis B, human papillomavirus, influenza, pneumococcal disease, tetanus). To summarise available data, we conducted a narrative synthesis. RESULTS: We included 78 studies/reports comprising 117 estimates of vaccination coverage across 36 countries. Most estimates were obtained from high income countries (80%, n=94). We located estimates for hepatitis B vaccination in 33 countries, which included 18 countries with data on serological evidence of vaccine-derived hepatitis B immunity (range: 6-53%) and 22 countries with self-report data for vaccine uptake (<1-96%). Data for other vaccines were scarcer: reported hepatitis A vaccination coverage ranged 3-89% (five countries), COVID-19 ranged 4-84% (five countries), while we located estimates from fewer than five countries for influenza, tetanus, pneumococcal disease, and human papillomavirus. CONCLUSION: Estimates were sparse but where available indicative of suboptimal vaccination coverage among people who inject drugs. Improving the consistency, timeliness, and geographic coverage of vaccine uptake data among this population is essential to inform efforts to increase uptake.

Predictors of engagement in screening for a hepatitis C virus (HCV) treatment trial in a rural Appalachian community.

An HCV treatment trial was initiated in September 2019 to address the opioid/hepatitis C virus (HCV) syndemic in rural Kentucky. The focus of the current analysis is on participation in diagnostic screening for the trial. Initial eligibility (≥18 years of age, county resident) was established by phone followed by in-person HCV viremia testing. 900 rural residents met the inclusion criteria and comprised the analytic sample. Generalized linear models were specified to estimate the relative risk of non-attendance at the in-person visit determining HCV eligibility. Approximately one-quarter (22.1%) of scheduled participants were no-shows. People who inject drugs were no more likely than people not injecting drugs to be a no-show; however, participants ≤35 years of age were significantly less likely to attend. While the median time between phone screening and scheduled in-person screening was only 2 days, each additional day increased the odds of no-show by 3% (95% confidence interval: 2%-3%). Finally, unknown HCV status predicted no-show even after adjustment for age, gender, days between screenings and injection status. We found that drug injection did not predict no-show, further justifying expanded access to HCV treatment among people who inject drugs. Those 35 years and younger were more likely to no-show, suggesting that younger individuals may require targeted strategies for increasing testing and treatment uptake. Finally, streamlining the treatment cascade may also improve outcomes, as participants in the current study were more likely to attend if there were fewer days between phone screening and scheduled in-person screening.

Hepatitis B Prevalence and Risk Factors in Punjab, India: A Population-Based Serosurvey.

Background: The prevalence of hepatitis B virus (HBV) infection in Punjab, India, is unknown. Understanding the statewide prevalence and epidemiology can help guide public health campaigns to reduce the burden of disease and promote elimination efforts. Methods: A cross-sectional, population-based survey was conducted from October 2013 to April 2014 using a multistage stratified cluster sampling design. All members of selected households aged ≥5 years were eligible. Participants were surveyed for demographics and risk behaviors; serum samples were tested for total antibody to hepatitis B core (total anti-HBc), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (anti-HCV), and HCV RNA. HBsAg-positive specimens were tested for HBV genotype. Results: A total of 5543 individuals participated in the survey and provided serum samples. The prevalence of total anti-HBc was 15.2% (95% confidence interval [95% CI]: 14.1-16.5) and HBsAg was 1.4% (95% CI: 1.0-1.9). Total anti-HBc positivity was associated with male sex (adjusted odds ratio [aOR] 1.46; 95% CI: 1.21-1.75), older age (aOR 3.31; 95% CI: 2.28-4.79 for ≥60 vs. 19-29 years), and living in a rural area (aOR 2.02; 95% CI: 1.62-2.51). Receipt of therapeutic injections in the past 6 months also increased risk (4-8 injections vs. none; aOR 1.39; 95% CI: 1.05-1.84). Among those positive for total anti-HBc, 10.4% (95% CI: 8.1-13.2) were also anti-HCV positive. Conclusion: Punjab has a substantial burden of HBV infection. Hepatitis B vaccination programs and interventions to minimize the use of therapeutic injections, particularly in rural areas, should be considered.

Cost-effectiveness of mass screening for Hepatitis C virus among all inmates in an Irish prison.

BACKGROUND: In Irish prisons, there is a high proportion of people who inject drugs (PWID; 26%) and a high prevalence of HCV (16%), making prison a high priority setting for HCV testing and treatment. We evaluate the cost-effectiveness of a mass HCV screening intervention in Mountjoy Prison, Dublin, compared to the standard-of-care of intermittent screening on committal. METHODS: Primary cost data was collected from the intervention using an overall provider perspective. Standard-of-care (SOC) costs were estimated through interview. All costs were inflated to 2020 Euros. An HCV transmission and disease progression model among incarcerated and community PWID and ex-injectors was calibrated to the Dublin HCV epidemic, allowing inclusion of population-level health benefits. The model used intervention data, suggesting 419 individuals were screened, 50 HCV infections diagnosed and 32 individuals initiated treatment, to project the resulting costs and health benefits (quality adjusted life years or QALYs) over 50 years with 5% discounting. The incremental cost effectiveness ratio (ICER), cost per QALY gained, was estimated for the screening intervention compared to the standard-of-care. Probabilistic sensitivity analyses (PSA) determined the probability that the intervention was cost-effective compared to a willingness-to-pay threshold of €30,000/QALY as used in Ireland. The ICER for 1- or 3-yearly mass screening in all Dublin prisons was also calculated. RESULTS: The total direct costs of the intervention (not including treatment drug costs) was €82,392, with most costs being due to staff (43%) and overhead or management costs (38%). Despite having little epidemiological impact due to the small numbers treated, over 50 years the incremental cost of the intervention was €36,592 and 3.8 QALYs were gained, giving a mean ICER of €9,552/QALY. The majority (84%) of PSA runs were below the willingness-to-pay threshold. Yearly mass screening had an ICER of €2,729/QALY compared to SOC and gave a higher net monetary benefit (€7,393,382) than screening every 3 years (€6,252,816). CONCLUSION: Prison mass screening could be a cost-effective initiative for increasing testing and treatment of HCV in Ireland.

Modelling the effect of market forces on the impact of introducing human immunodeficiency virus pre-exposure prophylaxis among female sex workers.

Pre-exposure prophylaxis (PrEP) to prevent human immunodeficiency virus (HIV) enables female sex workers (FSWs) to protect themselves from HIV without relying on clients using condoms. Yet, because PrEP reduces HIV risk, financial incentives to not use condoms may lead to risk compensation: reductions in condom use and/or increases in commercial sex, and may reduce the price of unprotected sex. In this analysis, we integrate market forces into a dynamic HIV transmission model to assess how risk compensation could change the impact of PrEP among FSWs and clients. We parameterise how sexual behavior may change with PrEP use among FSWs using stated preference data combined with economic theory. Our projections suggest the impact of PrEP is sensitive to risk compensatory behaviors driven by changes in the economics of sex work. Condom substitution could reduce the impact of PrEP on HIV incidence by 55%, while increases in the frequency of commercial sex to counter decreases in the price charged for unprotected sex among PrEP users could entirely mitigate the impact of PrEP. Accounting for competition between PrEP users and nonusers exacerbates this further. Alternative scenarios where increases in unprotected sex among PrEP users are balanced by decreases in non-PrEP users have the opposite effect, resulting in PrEP having much greater impact. Intervention studies need to determine how HIV prevention products may change the economics of sex work and provision of unprotected sex to enable a better understanding of their impact.

Cost-effectiveness of screening and treatment using direct-acting antivirals for chronic Hepatitis C virus in a primary care setting in Karachi, Pakistan.

Despite the availability of effective direct-acting antiviral (DAA) treatments for Hepatitis C virus (HCV) infection, many people remain undiagnosed and untreated. We assessed the cost-effectiveness of a Médecins Sans Frontières (MSF) HCV screening and treatment programme within a primary health clinic in Karachi, Pakistan. A health state transition Markov model was developed to estimate the cost-effectiveness of the MSF programme. Programme cost and outcome data were analysed retrospectively. The incremental cost-effectiveness ratio (ICER) was calculated in terms of incremental cost (2016 US$) per disability-adjusted life year (DALY) averted from the provider's perspective over a lifetime horizon. The robustness of the model was evaluated using deterministic and probabilistic sensitivity analyses (PSA). The ICER for implementing testing and treatment compared to no programme was US$450/DALY averted, with 100% of PSA runs falling below the per capita Gross Domestic Product threshold for cost-effective interventions for Pakistan (US$1,422). The ICER increased to US$532/DALY averted assuming national HCV seroprevalence (5.5% versus 33% observed in the intervention). If the cost of liver disease care was included (adapted from resource use data from Cambodia which has similar GDP to Pakistan), the ICER dropped to US$148/DALY, while it became cost-saving if a recently negotiated reduced drug cost of $75/treatment course was assumed (versus $282 in base-case) in addition to cost of liver disease care. In conclusion, screening and DAA treatment for HCV infection are expected to be highly cost-effective in Pakistan, supporting the expansion of similar screening and treatment programmes across Pakistan.

HIV prevention is not all about HIV - using a discrete choice experiment among women to model how the uptake and effectiveness of HIV prevention products may also rely on pregnancy and STI protection.

INTRODUCTION: In sub-Saharan Africa, considerable HIV-burden exists among women. Anti-retroviral (ARV) based prevention products could decrease this burden, and their uptake could be increased if they also protect against pregnancy and sexually transmitted infections (STI). METHODS: A discrete choice experiment (DCE) was undertaken in South Africa (2015) through a household survey of adult females (n = 158) and adolescent girls (n = 204) who self-reported HIV-negative status. The DCE was used to project the uptake (percentage using product) of oral pre-exposure prophylaxis (PrEP), vaginal rings, and injectable long-lasting ARV agents among these women, and how uptake could depend on whether these products protect against pregnancy or STI acquisition. Uptake estimates were used to model how each product could decrease a women's HIV acquisition risk. RESULTS: In adolescent women, there will be limited uptake (< 6% for any product) and impact (< 4% decrease in HIV acquisition risk) of new products unless they provide pregnancy protection, which could quadruple use and impact. Adult women have weaker preference for pregnancy protection, with moderate use (< 17% for each) and impact (< 14 percentage point decrease) if they only provide HIV protection. All women had highest preference for injectable ARVs, with oral PrEP having high preference if injectable ARVs are not available. Adult women will use the ring, but adolescent women will not. Importantly, even with three additional prevention products, all providing pregnancy and STI protection, > 14% of women will remain unprotected and > 31% of the baseline acquisition risk will remain. CONCLUSIONS: Incorporating multiple prevention components into new ARV-based prevention products may increase their uptake and impact among women.

An Economic Evaluation of the Cost-Effectiveness of Opt-Out Hepatitis B and Hepatitis C Testing in an Emergency Department Setting in the United Kingdom.

OBJECTIVES: The prevalence of hepatitis is high in emergency department (ED) attendees in the United Kingdom, with a prevalence of up to 2% for hepatitis B (HBV) HBsAg, and 2.9% for hepatitis C (HCV) RNA. The aim of this paper is to perform an economic evaluation of opt-out ED-based HCV and HBV testing. METHODS: A Markov model was developed to analyze the cost-effectiveness of opt-out HCV and HBV testing in EDs in the UK. The model used data from UK studies of ED testing to parameterize the HCV and HBV prevalence (1.4% HCV RNA, 0.84% HBsAg), test costs, and intervention effects (contact rates and linkage to care). For HCV, we used an antibody test cost of £3.64 and RNA test cost of £68.38, and assumed direct-acting antiviral treatment costs of £10 000. For HBV, we used a combined HBsAg and confirmatory test cost of £5.79. We also modeled the minimum prevalence of HCV (RNA-positive) and HBV (HBsAg) required to make ED testing cost-effective at a £20 000 willingness to pay per quality-adjusted life-year threshold. RESULTS: In the base case, ED testing was highly cost-effective, with HCV and HBV testing costing £8019 and £9858 per quality-adjusted life-year gained, respectively. HCV and HBV ED testing remained cost-effective at 0.25% HCV RNA or HBsAg prevalence or higher. CONCLUSIONS: Emergency department testing for HCV and HBV is highly likely to be cost-effective in many areas across the UK depending on their prevalence. Ongoing studies will help evaluate ED testing across different regions to inform testing guidelines.

Pay-it-forward gonorrhoea and chlamydia testing among men who have sex with men in China: a randomised controlled trial.

BACKGROUND: WHO recommends that men who have sex with men (MSM) receive gonorrhoea and chlamydia testing, but many evidence-based preventive services are unaffordable. The pay-it-forward strategy offers an individual a gift (eg, a test for sexually transmitted diseases) and then asks whether they would like to give a gift (eg, a future test) to another person. This study examined the effectiveness of a pay-it-forward programme to increase gonorrhoea and chlamydia testing among MSM in China. METHODS: We did a randomised controlled superiority trial at three HIV testing sites run by MSM community-based organisations in Guangzhou and Beijing, China. We included MSM aged 16 years or older who were seeking HIV testing and met indications for gonorrhoea and chlamydia testing. Restricted randomisation was done using computer-generated permuted blocks. 30 groups were randomised into three arms (1:1:1): a pay-it-forward arm in which men were offered free gonorrhoea and chlamydia testing and then asked whether they would like to donate for testing of prospective participants, a pay-what-you-want arm in which men were offered free testing and given the option to pay any desired amount for the test, and a standard-of-care arm in which testing was offered at ¥150 (US$22). There was no masking to arm assignment. The primary outcome was gonorrhoea and chlamydia test uptake ascertained by administrative records. We used generalised estimating equations to estimate intervention effects with one-sided 95% CIs and a prespecified superiority margin of 20%. The trial is registered with ClinicalTrials.gov, NCT03741725. FINDINGS: Between Dec 8, 2018, and Jan 19, 2019, 301 men were recruited and included in the analysis. 101 were randomly assigned to the pay-it-forward group, 100 to the pay-what-you-want group, and 100 to the standard-of-care group. Test uptake for gonorrhoea and chlamydia was 56% (57 of 101 participants) in the pay-it-forward arm, 46% (46 of 100 participants) in the pay-what-you-want arm, and 18% (18 of 100 participants) in the standard-of-care arm. The estimated difference in test uptake between the pay-it-forward and standard-of-care group was 38·4% (95% CI lower bound 28·4%). Among men in the pay-it-forward arm, 54 of 57 (95%) chose to donate to support testing for others. INTERPRETATION: The pay-it-forward strategy can increase gonorrhoea and chlamydia testing uptake among Chinese MSM and could be a useful tool for scaling up preventive services that carry a mandatory fee. FUNDING: US National Institute of Health; Special Programme for Research and Training in Tropical Diseases, sponsored by UNICEF, UNDP, World Bank, and WHO; the National Key Research and Development Program of China; Doris Duke Charitable Foundation; and Social Entrepreneurship to Spur Health.

Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis.

BACKGROUND: The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence. METHODS: We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018-30. We calibrated the model to country-level demographic data for 1960-2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007-08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs. FINDINGS: One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13·8 million (95% UI 13·4-14·1) individuals being screened and 350 000 (315 000-385 000) treatments started annually, decreasing hepatitis C incidence by 26·5% (22·5-30·7) over 2018-30. Prioritised screening of high prevalence groups (PWID and adults aged ≥30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46·8% and decrease incidence by 50·8% (95% UI 46·1-55·0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8·1 billion, reducing to $3·9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. INTERPRETATION: Pakistan will need to invest about 9·0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030. FUNDING: UNITAID.

Cost-effectiveness of the HepCATT intervention in specialist drug clinics to improve case-finding and engagement with HCV treatment for people who inject drugs in England.

BACKGROUND AND AIMS: People who inject drugs (PWID) are at high risk of hepatitis C virus (HCV) infection; however, ~50% are undiagnosed in England and linkage-to-care is poor. This study investigated the cost-effectiveness of an intervention (HepCATT) to improve case-finding and referral to HCV treatment compared with standard-of-care pathways in drug treatment centres in England. DESIGN: HCV transmission and disease progression model with cost-effectiveness analysis using a health-care perspective. Primary outcome and cost data from the HepCATT study parameterized the intervention, suggesting that HepCATT increased HCV testing in drug treatment centres 2.5-fold and engagement onto the HCV treatment pathway 10-fold. A model was used to estimate the decrease in HCV infections and HCV-related deaths from 2016, with costs and health benefits (quality-adjusted life-years or QALYs) tracked over 50 years. Univariable and probabilistic sensitivity analyses (PSA) were undertaken. SETTING: England-specific epidemic with 40% prevalence of chronic HCV among PWID. PARTICIPANTS: PWID attending drug treatment centres. INTERVENTION: Nurse facilitator in drug treatment centres to improve the HCV care pathway from HCV case-finding to referral and linkage to specialist care. Comparator was the standard-of-care HCV care pathway. MEASUREMENTS: Incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained through improved case-finding. FINDINGS: Over 50 years per 1000 PWID, the HepCATT intervention could prevent 75 (95% central interval 37-129) deaths and 1330 (827-2040) or 51% (30-67%) of all new infections. The mean ICER was £7986 per QALY gained, with all PSA simulations being cost-effective at a £20 000 per QALY willingness-to-pay threshold. Univariable sensitivity analyses suggest the intervention would become cost-saving if the cost of HCV treatment reduces to £3900. If scaled up to all PWID in England, the intervention would cost £8.8 million and decrease incidence by 56% (33-70%) by 2030. CONCLUSIONS: Increasing hepatitis C virus infection case-finding and treatment referral in drug treatment centres could be a highly cost-effective strategy for decreasing hepatitis C virus incidence among people who inject drugs.

The cost-effectiveness of an HCV outreach intervention for at-risk populations in London, UK.

BACKGROUND: HCV disproportionately affects marginalized communities such as homeless populations and people who inject drugs (PWID), posing a challenge to traditional health services. The HepFriend initiative in London is a model of care utilizing HCV outreach screening and peer support to link vulnerable individuals to HCV treatment in secondary care. OBJECTIVES: To assess the cost-effectiveness of the HepFriend initiative from a healthcare provider perspective, compared with standard-of-care pathways (consisting of testing in primary care and other static locations, including drug treatment centres, and linkage to secondary care). METHODS: Cost-effectiveness analysis using a dynamic HCV transmission and disease progression model among PWID and those who have ceased injecting, including housing status and drug treatment service contact. The model was parameterized using London-specific surveillance and survey data, and primary intervention cost and effectiveness data (September 2015 to June 2018). Out of 461 individuals screened, 197 were identified as HCV RNA positive, 180 attended secondary care and 89 have commenced treatment to date. The incremental cost-effectiveness ratio (ICER) was determined using a 50 year time horizon. RESULTS: For a willingness-to-pay threshold of £20000 per QALY gained, the HepFriend initiative is cost-effective, with a mean ICER of £9408/QALY, and would become cost saving at 27% (£10525 per treatment) of the current drug list price. Results are robust to variations in intervention costs and model assumptions, and if treatment rates are doubled the intervention becomes more cost-effective (£8853/QALY). CONCLUSIONS: New models of care that undertake active case-finding with enhanced peer support to improve testing and treatment uptake amongst marginalized and vulnerable groups could be highly cost-effective and possibly cost saving.

Cost-Effectiveness of One-Time Birth Cohort Screening for Hepatitis C as Part of the National Health Service Health Check Program in England.

BACKGROUND AND OBJECTIVES: Birth cohort screening for the hepatitis C virus (HCV) has been implemented in the US, but there is little evidence of its cost-effectiveness in England. We aim to evaluate the cost-effectiveness of one-time HCV screening for individuals born between 1950 and 1979 as part of the National Health Service health check in England, a health check for adults aged 40 to 74 years in primary care. METHODS: A Markov model was developed to analyze add-on HCV testing to the National Health Service health check for individuals in birth cohorts between 1950 and 1979, versus current background HCV testing only, over a lifetime horizon. The model used data from a back-calculation model of the burden of HCV in England, sentinel surveillance of HCV testing, and published literature. Results are presented from a health service perspective in pounds in 2017, as incremental cost-effectiveness ratios per quality-adjusted life years gained. RESULTS: The base-case incremental cost-effectiveness ratios ranged from £7648 to £24 434, and £18 681 to £46 024, across birth cohorts when considering 2 sources of HCV transition probabilities. The intervention is most likely to be cost-effective for those born in the 1970s, and potentially cost-effective for those born from 1955 to 1969. The model results were most sensitive to the source of HCV transition probabilities, the probability of referral and receiving treatment, and the HCV prevalence among testers. The maximum value of future research across all birth cohorts was £11.3 million at £20 000 per quality-adjusted life years gained. CONCLUSION: Birth cohort screening is likely to be cost-effective for younger birth cohorts, although considerable uncertainty exists for other birth cohorts. Further studies are warranted to reduce uncertainty in cost-effectiveness and consider the acceptability of the intervention.

Pay-it-forward gonorrhea and chlamydia testing among men who have sex with men in China: a study protocol for a three-arm cluster randomized controlled trial.

BACKGROUND: Gonorrhea and chlamydia testing rates are poor among Chinese men who have sex with men (MSM). A quasi-experimental study suggested that a pay-it-forward strategy increased dual gonorrhea/chlamydia testing among MSM. Pay-it-forward offers an individual a gift (e.g., a free test) and then asks the same person if they would like to give a gift to another person. This article reports the protocol of a randomized controlled trial to evaluate dual gonorrhea/chlamydia test uptake and other outcomes among MSM in three arms - a pay-it-forward arm, a pay-what-you-want arm, and a standard of care arm. METHODS: Three hundred MSM will be recruited at three HIV testing sites in Guangzhou and Beijing. Testing sites include two hospital-based MSM sexually transmitted diseases clinics and one MSM community-based organization. Eligible participants will be born biologically male, aged 16 years or older, reporting previous anal sex with another man, having never participated in the pay-it-forward program, without previous gonorrhea and chlamydia testing in the past 12 months, and residing in China. Following a cluster randomized design, every cluster of ten participants will be randomly allocated into one of three arms: (1) a pay-it-forward arm in which men are offered free gonorrhea and chlamydia testing and then asked whether they would like to donate ("pay it forward") toward testing for future testers; (2) a pay-what-you-want arm in which men are offered free testing and told to decide how much to pay after receiving the test; (3) a standard of care arm in which men can pay the full price for dual gonorrhoea and chlamydia testing. The primary outcome is dual gonorrhoea/chlamydia testing as verified by administrative records. Secondary outcomes include incremental cost per test, incremental cost per diagnosis, community connectedness, and social cohesion. Primary outcome will be calculated for each arm using intention-to-treat and compared using one-sided 95% confidence intervals with a margin of 20% increase defined as superiority. DISCUSSION: This study will examine the pay-it-forward strategy in comparison to the standard of care in improving test uptake for gonorrhea and chlamydia. We will leverage the cluster randomized controlled trial to provide scientific evidence on the potential effect of pay-it-forward. Findings from this study will shed light on novel intervention methods for increasing preventive health service utilization and innovate ways to finance it among communities. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03741725 . Registered on 12 November 2018.

Determinants of heterosexual men's demand for long-acting injectable pre-exposure prophylaxis (PrEP) for HIV in urban South Africa.

BACKGROUND: Heterosexual men in South Africa are a large key population to exposure to HIV, yet preferences for HIV pre-exposure prophylaxis (PrEP) among this population have not, to date, been investigated in the literature. This paper aims to explore HIV prevention preferences among heterosexual men in urban South Africa, as well as to examine the demand and characteristics of men who favour long-acting injectable (LAI) PrEP over condoms and oral PrEP. METHODS: Data were collected among 178 self-reported HIV-negative heterosexual men, who were given example products and information before being asked which they preferred. Multivariate logistic regression was used to analyse which characteristics were associated with product choice. RESULTS: 48% (n = 85) of participants preferred LAI PrEP, while 33% (n = 58) and 20% (n = 35) chose oral PrEP and condoms respectively. Having children (marginal effect = 0.22; 95% CI [0.01, 0.44]) or having higher risk attitude scores (marginal effect = 0.03; 95% CI [0.01, 0.06]) was significantly associated with a choice of LAI PrEP, while those who had unprotected anal intercourse (marginal effect = - 0.42; 95% CI [- 0.57, - 0.27]) and those who were concerned with protection against other sexually transmitted infections over HIV (marginal effect = - 0.42; 95% CI [- 0.60, - 0.24]) appeared less likely to prefer LAI PrEP. CONCLUSIONS: The results suggested a relatively high demand and theoretical acceptability for LAI PrEP among heterosexual men in urban South Africa, but there appeared to be fewer distinct predictors for the willingness to use LAI PrEP compared to studies conducted among gay and bisexual men and women. Nevertheless, the findings contribute to the mapping of the demand and determinants of heterosexual men's preferences for novel antiretroviral-based prevention in sub-Saharan Africa, and the data could aid in the differentiated design of future HIV prevention strategies using LAI PrEP in conjunction with other methods.

A Global Meta-analysis of the Prevalence of HIV, Hepatitis C Virus, and Hepatitis B Virus Among People Who Inject Drugs-Do Gender-Based Differences Vary by Country-Level Indicators?

BACKGROUND: Women-specific factors exist that increases vulnerability to drug-related harms from injection drug use, including blood-borne viruses (BBVs), but gender-based differences in BBV prevalence have not been systematically examined. METHODS: We conducted meta-analyses to estimate country, regional, and global prevalence of serologically confirmed human immunodeficiency virus (HIV), hepatitis C virus (HCV; based on detection of anti-HCV antibody), and hepatitis B virus (HBV; based on detection of HBV surface antigen) in people who inject drugs (PWID), by gender. Gender-based differences in the BBV prevalence (calculated as the risk among women relative to the risk among men) were regressed on country-level prevalence and inequality measures (Gender inequality index, Human development index, Gini coefficient, and high, low or middle income of the country). RESULTS: Gender-based differences varied by countries and regions. HIV prevalence was higher among women than men in sub-Saharan Africa (relative risk [RR], 2.8; 95% confidence interval [CI], 1.8-4.4) and South Asia (RR, 1.7; 95% CI, 1.1-2.7); anti-HCV was lower among women in the Middle East and North Africa (RR, 0.6; 95% CI, .5-.7) and East and Southeast Asia (RR, 0.8; 95% CI, .7-.9). Gender-based differences varied with country-levels of the BBV prevalence in the general population, human development, and income distribution. CONCLUSION: HIV was more prevalent in women who inject drugs as compared to their male counterparts in some countries, but there is variation between and within regions. In countries where women are at higher risks, there is a need to develop gender-sensitive harm-reduction services for the particularly marginalized population of women who inject drugs.

Crowdsourcing to expand HIV testing among men who have sex with men in China: A closed cohort stepped wedge cluster randomized controlled trial.

BACKGROUND: HIV testing rates are suboptimal among at-risk men. Crowdsourcing may be a useful tool for designing innovative, community-based HIV testing strategies to increase HIV testing. The purpose of this study was to use a stepped wedge cluster randomized controlled trial (RCT) to evaluate the effect of a crowdsourced HIV intervention on HIV testing uptake among men who have sex with men (MSM) in eight Chinese cities. METHODS AND FINDINGS: An HIV testing intervention was developed through a national image contest, a regional strategy designathon, and local message contests. The final intervention included a multimedia HIV testing campaign, an online HIV testing service, and local testing promotion campaigns tailored for MSM. This intervention was evaluated using a closed cohort stepped wedge cluster RCT in eight Chinese cities (Guangzhou, Shenzhen, Zhuhai, and Jiangmen in Guangdong province; Jinan, Qingdao, Yantai, and Jining in Shandong province) from August 2016 to August 2017. MSM were recruited through Blued, a social networking mobile application for MSM, from July 29 to August 21 of 2016. The primary outcome was self-reported HIV testing in the past 3 months. Secondary outcomes included HIV self-testing, facility-based HIV testing, condom use, and syphilis testing. Generalized linear mixed models (GLMMs) were used to analyze primary and secondary outcomes. We enrolled a total of 1,381 MSM. Most were ≤30 years old (82%), unmarried (86%), and had a college degree or higher (65%). The proportion of individuals receiving an HIV test during the intervention periods within a city was 8.9% (95% confidence interval [CI] 2.2-15.5) greater than during the control periods. In addition, the intention-to-treat analysis showed a higher probability of receiving an HIV test during the intervention periods as compared to the control periods (estimated risk ratio [RR] = 1.43, 95% CI 1.19-1.73). The intervention also increased HIV self-testing (RR = 1.89, 95% CI 1.50-2.38). There was no effect on facility-based HIV testing (RR = 1.00, 95% CI 0.79-1.26), condom use (RR = 1.00, 95% CI 0.86-1.17), or syphilis testing (RR = 0.92, 95% CI 0.70-1.21). A total of 48.6% (593/1,219) of participants reported that they received HIV self-testing. Among men who received two HIV tests, 32 individuals seroconverted during the 1-year study period. Study limitations include the use of self-reported HIV testing data among a subset of men and non-completion of the final survey by 23% of participants. Our study population was a young online group in urban China and the relevance of our findings to other populations will require further investigation. CONCLUSIONS: In this setting, crowdsourcing was effective for developing and strengthening community-based HIV testing services for MSM. Crowdsourced interventions may be an important tool for the scale-up of HIV testing services among MSM in low- and middle-income countries (LMIC). TRIAL REGISTRATION: ClinicalTrials.gov NCT02796963.

Global population-level association between herpes simplex virus 2 prevalence and HIV prevalence.

BACKGROUND: Our objective was to assess the population-level association between herpes simplex virus 2 (HSV-2) and HIV prevalence. METHODS: Reports of HSV-2 and HIV prevalence were systematically reviewed and synthesized following PRISMA guidelines. Spearman rank correlation ((Equation is included in full-text article.)) was used to assess correlations. Risk ratios (RRHSV-2/HIV) and odds ratios (ORHSV-2/HIV) were used to assess HSV-2/HIV epidemiologic overlap. DerSimonian-Laird random-effects meta-analyses were conducted. RESULTS: In total, 939 matched HSV-2/HIV prevalence measures were identified from 77 countries. HSV-2 prevalence was consistently higher than HIV prevalence. Strong HSV-2/HIV prevalence association was found for all data ((Equation is included in full-text article.) = 0.6, P < 0.001), all data excluding people who inject drugs (PWID) and children ((Equation is included in full-text article.) = 0.7, P < 0.001), female sex workers ((Equation is included in full-text article.) = 0.5, P < 0.001), and MSM ((Equation is included in full-text article.) = 0.7, P < 0.001). No association was found for PWID ((Equation is included in full-text article.) = 0.2, P = 0.222) and children ((Equation is included in full-text article.) = 0.3, P = 0.082). A threshold effect was apparent where HIV prevalence was limited at HSV-2 prevalence less than 20%, but grew steadily with HSV-2 prevalence for HSV-2 prevalence greater than 20%. The overall pooled mean RRHSV-2/HIV was 5.0 (95% CI 4.7-5.3) and ORHSV-2/HIV was 9.0 (95% CI 8.4-9.7). The RRHSV-2/HIV and ORHSV-2/HIV showed similar patterns that conveyed inferences about HSV-2 and HIV epidemiology. CONCLUSION: HSV-2 and HIV prevalence are strongly associated. HSV-2 prevalence can be used as a proxy 'biomarker' of HIV epidemic potential, acting as a 'temperature scale' of the intensity of sexual risk behavior that drive HIV transmission. HSV-2 prevalence can be used to identify populations and/or sexual networks at high-risk of future HIV expansion, and help prioritization, optimization, and resource allocation of cost-effective prevention interventions.

Importance and Contribution of Community, Social, and Healthcare Risk Factors for Hepatitis C Infection in Pakistan.

Pakistan has a high prevalence of hepatitis C virus (HCV) infection, estimated at 4.9% (2,290/46,843) in the 2007 national HCV seroprevalence survey. We used data from this survey to assess the importance of risk factor associations with HCV prevalence in Pakistan. Exposures were grouped as community (going to the barbers, sharing smoking equipment, having an ear/nose piercing, tattoo, or acupuncture), healthcare (ever having hemodialysis, blood transfusion, or ≥ 5 injections in the last year), demographic (marital status and age), and socio-economic (illiterate or laborer). We used mutually adjusted multivariable regression analysis, stratified by sex, to determine associations with HCV infection, their population attributable fraction, and how risk of infection accumulates with multiple exposures. Strength of associations was assessed using adjusted odds ratios (aOR). Community [aOR females 1.5 (95% confidence interval [CI]: 1.2, 1.8); males 1.2 (1.1, 1.4)] and healthcare [females 1.4 (1.2, 1.6); males 1.2 (1.1, 1.4)] exposures, low socio-economic status [females 1.6 (1.3, 1.80); males 1.3 (1.2, 1.5)], and marriage [females 1.5 (1.2, 1.9); males 1.4 (1.1, 1.8)] were associated with increased HCV infection. Among married women, the number of children was associated with an increase in HCV infection; linear trend aOR per child 1.06 (1.01, 1.11). Fewer infections could be attributed to healthcare exposures (females 13%; males 6%) than to community exposures (females 25%; males 9%). Prevalence increased from 3% to 10% when cumulative exposures increased from 1 to ≥ 4 [aOR per additional exposure for females 1.5 (1.4, 1.6); males 1.2 (1.2, 1.3)]. A combination of community, healthcare, and other factors appear to drive the Pakistan HCV epidemic, highlighting the need for a comprehensive array of prevention strategies.