Correction: Health and economic benefits of achieving hepatitis C virus elimination in Pakistan: A modelling study and economic analysis.

[This corrects the article DOI: 10.1371/journal.pmed.1003818.].

Changes in the prevalence of hepatitis B and C viral infections in Sindh province, Pakistan: Findings from two sero-surveys in 2007 and 2019.

Pakistan harbours a large burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We utilised repeat sero-surveys to assess progress achieved towards hepatitis elimination in Pakistan. Multilevel logistic regression evaluated the change in HBV infection (HBV surface antigen (HBsAg)-positive) prevalence and HCV exposure (HCV antibody (HCV-Ab)-positive) prevalence between two sero-surveys from 2007 and 2019 for Sindh province and associated risk factors. Adjusted odds ratios (aORs) were estimated and population-attributable fractions (PAF) for modifiable risk factors for HCV exposure. The 2007 and 2019 surveys included 8855 and 6672 individuals. HBsAg prevalence decreased from 2.6% (95% confidence intervals (95% CI): 2.2-2.9) in 2007 to 1.1% (95% CI: 0.8-1.3) in 2019, while HCV-Ab prevalence increased from 5.1% (95% CI: 4.6%-5.5%) to 6.2% (95% CI: 5.6%-6.8%). The age and gender-adjusted HBsAg prevalence decreased by 80% (aOR = 0.2, 95% CI: 0.1-0.4) among children and 60% (aOR = 0.4, 95% CI: 0.3-0.6) among adults over 2007-2019, while HCV-Ab prevalence decreased by 60% (aOR = 0.4, 95%CI:0.2-0.7) in children and increased by 40% (aOR = 1.4, 95% CI: 1.2-1.7) in adults. HCV-Ab prevalence was lower in adults with secondary (aOR = 0.6, 95% CI: 0.5-0.8) and higher (aOR = 0.5, 95%CI:0.3-0.8) education compared to illiterates and higher among adults reporting blood transfusion (aOR = 1.7, 95% CI: 1.2-2.4), family history of hepatitis (aOR = 2.5, 95% CI: 1.9-3.3), past year medical injection (aOR = 2.1, 95% CI: 1.6-2.7), being tattooed (aOR = 1.4, 95% CI: 1.0-1.9) and shaved by traditional barber (aOR = 1.2, 95% CI: 1.0-1.5). Modifiable risk factors accounted for 45% of HCV exposure, with medical injection(s) accounting for 38% (95%CI,25.7-48.4%). Overall HCV has increased over 2007-2019 in Sindh province, while HBV prevalence has decreased. Medical injections should be an important focus of prevention activities.

Prevalence, trends, and distribution of hepatitis C virus among the general population in sub-Saharan Africa: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Although the evidence is uncertain, existing estimates for hepatitis C virus (HCV) in sub-Saharan Africa (SSA) indicate a high burden. We estimated HCV seroprevalence and viraemic prevalence among the general population in SSA. METHODS: We searched Medline, Embase, Web of Science, APA PsycINFO, and World Health Organization Africa Index Medicus for community-based studies. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool, and heterogeneity using the index of heterogeneity (I2). Two approaches were deployed. First, we used random-effects meta-analysis to pool prevalence. Second, to derive representative estimates, we weighted each country's HCV seroprevalence using 2021 United Nations country population sizes. RESULTS: We synthesized 130 studies. Overall, SSA HCV seroprevalence from the random-effects model was 4.17% (95% confidence interval [CI]: 3.71-4.66, I2 = 99.30%). There were no differences between males (4.31%) and females (4.03%). Seroprevalence was 2.25%, 3.31%, and 16.23% for ages ≤20, 21-64, and ≥65 years, respectively, and was higher in rural (6.63%) versus urban (2.93%). There was indication of decrement overtime from 5.74% to 4.35% to 3.03% in the years 1984-2000, 2001-2014, and 2015-2023, respectively. The weighted overall SSA HCV seroprevalence was estimated to be 2.30% (95% CI: 1.59-3.00) with regional variation: Africa-Southern (.79%), Africa-Central (1.47%), Africa-Eastern (2.71%), and Africa-Western (2.88%). HCV viremia among HCV seropositives was 54.77% (95% CI: 47.80-61.66). CONCLUSIONS: HCV seroprevalence in SSA remains high. Populations aged ≥65 years, rural communities, Africa-Western, and some countries in Africa-Central and Africa-Eastern appear disproportionately affected. These results underline the need for governmental commitment to achieve the 2030 global HCV elimination targets.

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.

Estimates of hepatitis B virus prevalence among general population and key risk groups in EU/EEA/UK countries: a systematic review.

BackgroundThe burden of chronic hepatitis B virus (HBV) varies across the European Union (EU) and European Economic Area (EEA).AimWe aimed to update the 2017 HBV prevalence estimates in EU/EEA countries and the United Kingdom for 2018 to 2021.MethodsWe undertook a systematic review, adding to HBV prevalence estimates from an existing (2005-2017) database. Databases were searched for original English-language research articles including HBV surface antigen prevalence estimates among the general population, pregnant women, first-time blood donors (FTB), men who have sex with men (MSM), migrants and people in prison. Country experts contributed grey literature data. Risk of bias was assessed using a quality assessment framework.FindingsThe update provided 147 new prevalence estimates across the region (updated total n = 579). Median HBV prevalence in the general population was 0.5% and the highest was 3.8% (Greece). Among FTB, the highest prevalence was 0.8% (Lithuania). Estimates among pregnant women were highest in Romania and Italy (5.1%). Among migrants, the highest estimate was 31.7% (Spain). Relative to 2017 estimates, median prevalence among pregnant women decreased by 0.5% (to 0.3%) and increased by 0.9% (to 5.8%) among migrants. Among MSM, the highest estimate was 3.4% (Croatia). Prevalence among people in prison was highest in Greece (8.3%) and the median prevalence increased by 0.6% (to 2.1%).ConclusionsThe HBV prevalence is low in the general population and confined to risk populations in most European countries with some exceptions. Screening and treatment should be targeted to people in prison and migrants.

Evaluating the Prevention Benefit of HCV Treatment: Modeling the SToP-C Treatment as Prevention Study in Prisons.

BACKGROUND AND AIMS: Between 2014 and 2019, the SToP-C trial observed a halving in HCV incidence in four Australian prisons following scale-up of direct-acting antiviral (DAA) therapy. However, the contribution of HCV treatment to this decline is unclear because the study did not have a control group. We used modeling to consider this question. APPROACH AND RESULTS: We parameterized and calibrated a dynamic model of HCV transmission in prisons to data from each SToP-C prison on incarceration dynamics, injecting drug use, HCV prevalence trends among prison entrants, baseline HCV incidence before treatment scale-up, and subsequent HCV treatment scale-up. The model projected the decrease in HCV incidence resulting from increases in HCV treatment and other effects. We assessed whether the model agreed better with observed reductions in HCV incidence overall and by prison if we included HCV treatment scale-up, and its prevention benefits, or did not. The model estimated how much of the observed decrease in HCV incidence was attributable to HCV treatment in prison. The model projected a decrease in HCV incidence of 48.5% (95% uncertainty interval [UI], 41.9-54.1) following treatment scale-up across the four prisons, agreeing with the observed HCV incidence decrease (47.6%; 95% CI, 23.4-64.2) from the SToP-C trial. Without any in-prison HCV treatment, the model indicated that incidence would have decreased by 7.2% (95% UI, -0.3 to 13.6). This suggests that 85.1% (95% UI, 72.6-100.6) of the observed halving in incidence was from HCV treatment scale-up, with the remainder from observed decreases in HCV prevalence among prison entrants (14.9%; 95% UI, -0.6 to 27.4). CONCLUSIONS: Our results demonstrate the prevention benefits of scaling up HCV treatment in prison settings. Prison-based DAA scale-up should be an important component of HCV elimination strategies.

Health and economic benefits of achieving hepatitis C virus elimination in Pakistan: A modelling study and economic analysis.

BACKGROUND: Modelling suggests that achieving the WHO incidence target for hepatitis C virus (HCV) elimination in Pakistan could cost US$3.87 billion over 2018 to 2030. However, the economic benefits from integrating services or improving productivity were not included. METHODS AND FINDINGS: We adapt a HCV transmission model for Pakistan to estimate the impact, costs, and cost-effectiveness of achieving HCV elimination (reducing annual HCV incidence by 80% by 2030) with stand-alone service delivery, or partially integrating one-third of initial HCV testing into existing healthcare services. We estimate the net economic benefits by comparing the required investment in screening, treatment, and healthcare management to the economic productivity gains from reduced HCV-attributable absenteeism, presenteeism, and premature deaths. We also calculate the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for HCV elimination versus maintaining current levels of HCV treatment. This is compared to an opportunity cost-based willingness-to-pay threshold for Pakistan (US$148 to US$198/DALY). Compared to existing levels of treatment, scaling up screening and treatment to achieve HCV elimination in Pakistan averts 5.57 (95% uncertainty interval (UI) 3.80 to 8.22) million DALYs and 333,000 (219,000 to 509,000) HCV-related deaths over 2018 to 2030. If HCV testing is partially integrated, this scale-up requires an investment of US$1.45 (1.32 to 1.60) billion but will result in US$1.30 (0.94 to 1.72) billion in improved economic productivity over 2018 to 2030. This elimination strategy is highly cost-effective (ICER = US$29 per DALY averted) by 2030, with it becoming cost-saving by 2031 and having a net economic benefit of US$9.10 (95% UI 6.54 to 11.99) billion by 2050. Limitations include uncertainty around what level of integration is possible within existing primary healthcare services as well as a lack of Pakistan-specific data on disease-related healthcare management costs or productivity losses due to HCV. CONCLUSIONS: Investment in HCV elimination can bring about substantial societal health and economic benefits for Pakistan.

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.

Modelling the potential prevention benefits of a treat-all hepatitis C treatment strategy at global, regional and country levels: A modelling study.

The World Health Organization (WHO) recently produced guidelines advising a treat-all policy for HCV to encourage widespread treatment scale-up for achieving HCV elimination. We modelled the prevention impact achieved (HCV infections averted [IA]) from initiating this policy compared with treating different subgroups at country, regional and global levels. We assessed what country-level factors affect impact. A dynamic, deterministic HCV transmission model was calibrated to data from global systematic reviews and UN data sets to simulate country-level HCV epidemics with ongoing levels of treatment. For each country, the model projected the prevention impact (in HCV IA per treatment undertaken) of initiating four treatment strategies; either selected randomly (treat-all) or targeted among people who inject drugs (PWID), people aged ≥35, or those with cirrhosis. The IA was assessed over 20 years. Linear regression was used to identify associations between IA per treatment and demographic factors. Eighty-eight countries (85% of the global population) were modelled. Globally, the model estimated 0.35 (95% credibility interval [95%CrI]: 0.16-0.61) IA over 20 years for every randomly allocated treatment, 0.30 (95%CrI: 0.12-0.53) from treating those aged ≥35 and 0.28 (95%CrI: 0.12-0.49) for those with cirrhosis. Globally, treating PWID achieved 1.27 (95%CrI: 0.68-2.04) IA per treatment. The IA per randomly allocated treatment was positively associated with a country's population growth rate and negatively associated with higher HCV prevalence among PWID. In conclusion, appreciable prevention benefits could be achieved from WHO's treat-all strategy, although greater benefits per treatment can be achieved through targeting PWID. Higher impact will be achieved in countries with high population growth.

Larger mammalian body size leads to lower retroviral activity.

Retroviruses have been infecting mammals for at least 100 million years, leaving descendants in host genomes known as endogenous retroviruses (ERVs). The abundance of ERVs is partly determined by their mode of replication, but it has also been suggested that host life history traits could enhance or suppress their activity. We show that larger bodied species have lower levels of ERV activity by reconstructing the rate of ERV integration across 38 mammalian species. Body size explains 37% of the variance in ERV integration rate over the last 10 million years, controlling for the effect of confounding due to other life history traits. Furthermore, 68% of the variance in the mean age of ERVs per genome can also be explained by body size. These results indicate that body size limits the number of recently replicating ERVs due to their detrimental effects on their host. To comprehend the possible mechanistic links between body size and ERV integration we built a mathematical model, which shows that ERV abundance is favored by lower body size and higher horizontal transmission rates. We argue that because retroviral integration is tumorigenic, the negative correlation between body size and ERV numbers results from the necessity to reduce the risk of cancer, under the assumption that this risk scales positively with body size. Our model also fits the empirical observation that the lifetime risk of cancer is relatively invariant among mammals regardless of their body size, known as Peto's paradox, and indicates that larger bodied mammals may have evolved mechanisms to limit ERV activity.

HTLV-I infection: a dynamic struggle between viral persistence and host immunity.

Human T-lymphotropic virus type I (HTLV-I) causes chronic infection for which there is no cure or neutralising vaccine. HTLV-I has been clinically linked to the development of adult T-cell leukaemia/lymphoma (ATL), an aggressive blood cancer, and HAM/TSP, a progressive neurological and inflammatory disease. Infected individuals typically mount a large, persistently activated CD8(+) cytotoxic T-lymphocyte (CTL) response against HTLV-I-infected cells, but ultimately fail to effectively eliminate the virus. Moreover, the identification of determinants to disease manifestation has thus far been elusive. A key issue in current HTLV-I research is to better understand the dynamic interaction between persistent infection by HTLV-I and virus-specific host immunity. Recent experimental hypotheses for the persistence of HTLV-I in vivo have led to the development of mathematical models illuminating the balance between proviral latency and activation in the target cell population. We investigate the role of a constantly changing anti-viral immune environment acting in response to the effects of infected T-cell activation and subsequent viral expression. The resulting model is a four-dimensional, non-linear system of ordinary differential equations that describes the dynamic interactions among viral expression, infected target cell activation, and the HTLV-I-specific CTL response. The global dynamics of the model is established through the construction of appropriate Lyapunov functions. Examining the particular roles of viral expression and host immunity during the chronic phase of HTLV-I infection offers important insights regarding the evolution of viral persistence and proposes a hypothesis for pathogenesis.

Effects and Costs of Hepatitis C Virus Elimination for the Whole Population in China: A Modelling Study.

BACKGROUND AND OBJECTIVE: China has the highest number of hepatitis C virus (HCV) infections in the world. However, it is unclear what levels of screening and treatment are needed to achieve the WHO 2030 hepatitis C elimination targets. We aimed to evaluate the impact of scaling up interventions on the hepatitis C epidemic and determine how and at what cost these elimination targets could be achieved for the whole population in China. METHODS: We developed a compartmental model incorporating HCV transmission, disease progression, and care cascade for the whole population in China, calibrated with data on demographics, injecting drug use, HCV prevalence, and treatments. Five different scenarios were evaluated for effects and costs for 2022-2030. All costs were converted to 2021 US dollar (USD) and discounted at an annual rate of 5%. One-way sensitivity analyses were conducted to assess the robustness of the model. RESULTS: Under the status quo scenario, the incidence of hepatitis C is projected to increase from 60.39 (57.60-63.45) per 100,000 person-years in 2022 to 68.72 (65.3-73.97) per 100,000 person-years in 2030, and 2.52 million (1.94-3.07 million) infected patients are projected to die between 2022 and 2030, of which 0.76 (0.61-1.08) million will die due to hepatitis C. By increasing primary screening to 10%, conducting regular rescreening (annually for PWID and every 5 years for the general population) and treating 90% of patients diagnosed, the incidence would be reduced by 88.15% (86.61-89.45%) and hepatitis C-related mortality by 60.5% (52.62-65.54%) by 2030, compared with 2015 levels. This strategy would cost USD 52.78 (USD 43.93-58.53) billion. CONCLUSIONS: Without changes in HCV prevention and control policy, the disease burden of HCV in China will increase dramatically. To achieve the hepatitis C elimination targets, China needs to sufficiently scale up screening and treatment.

Effect of integrated hepatitis C virus treatment on psychological distress in people with substance use disorders.

People with substance use disorders (SUD) have a high prevalence of chronic hepatitis C virus (HCV) infection and mental health disorders. We aimed to assess the impact of integrated HCV treatment on psychological distress measured by Hopkins-symptom-checklist-10 (SCL-10). This multi-center randomized controlled trial evaluated psychological distress as a secondary outcome of integrated HCV treatment (INTRO-HCV trial). From 2017 to 2019, 289 participants were randomly assigned to receive either integrated or standard HCV treatment with direct-acting antiviral therapy. Integrated HCV treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in internal medicine outpatient clinics at centralized hospitals. Participants in the integrated treatment arm had a sustained virologic response of 93% compared to 73% for those in standard treatment arm. Psychological distress was assessed using SCL-10 prior to initiation of HCV treatment and 12 weeks after treatment completion. The mean SCL-10 score prior to HCV treatment was 2.2 (standard deviation [SD]: 0.7) for patients receiving integrated HCV treatment and 2.2 (SD: 0.8) for those receiving standard HCV treatment. Twelve weeks after the end of treatment, the mean SCL-10 score change was - 0.1 (- 0.3;0.0) in the integrated compared to the standard arm. Psychological distress did not substantially change during the treatment period and was not significantly different between the treatment arms.

The efficacy of integrated hepatitis C virus treatment in relieving fatigue in people who inject drugs: a randomized controlled trial.

BACKGROUND: Most people who inject drugs (PWIDs) suffer from severe fatigue, and chronic hepatitis C virus (HCV) infection may play a role in this. However, there is scarce evidence about interventions that alleviate fatigue among PWIDs. The present study investigated the effect of integrated HCV treatment on fatigue in this population compared to the effect of standard HCV treatment, adjusted for sustained virological response of the HCV treatment. METHODS: This multi-center, randomized controlled trial evaluated fatigue as a secondary outcome of integrated HCV treatment (the INTRO-HCV trial). From May 2017 to June 2019, 276 participants in Bergen and Stavanger, Norway, were randomly assigned to receive integrated and standard HCV treatment. Integrated treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in specialized infectious disease outpatient clinics at referral hospitals. Fatigue was assessed prior to treatment and 12 weeks after treatment using the nine-item Fatigue Severity Scale (FSS-9). We applied a linear mixed model to evaluate the impact of integrated HCV treatment on changes in FSS-9 (ΔFSS-9) sum scores. RESULTS: At baseline, the mean FSS-9 sum score was 46 (standard deviation (SD): 15) for participants on integrated HCV treatment and 41 (SD: 16) for those on standard treatment. Twelve weeks after completed HCV treatment, the mean FSS-9 sum score for participants receiving integrated HCV treatment was 42 (SD: 15) and 40 (SD: 14) for those receiving standard HCV treatment. Integrated HCV treatment did not reduce the FSS-9 scores compared to standard HCV treatment (ΔFSS-9: -3.0, 95% confidence interval (CI): -6.4;0.4). CONCLUSIONS: Fatigue is a common symptom among PWIDs. Integrated HCV treatment is at least equal to standard HCV treatment in improving fatigue. TRIAL REGISTRATION: ClinicalTrials.gov.no NCT03155906, 16/05/2017.

Risk factors of HIV and variation in access to clean needles among people who inject drugs in Pakistan.

We identified key risk factors for HIV among people who inject drugs (PWID) in Pakistan and explored access to free clean needles. Multivariable logistic regression was used to investigate associations between HIV prevalence and demographic, behavioral, and socio-economic characteristics of PWID. Data came from the Government of Pakistan's Integrated Biological and Behavioral Surveillance (IBBS) Round 5 (2016-17; 14 cities). A secondary analysis investigated associations with reported access to clean needles. Unweighted HIV prevalence among 4,062 PWID (99% male) was 21.0%. Longer injecting duration (Odds ratio [OR] 1.06 [95% confidence interval: 1.02-1.10]; per year), higher injecting frequency (OR 1.67 [1.30-2.13]; per unit increase), and injecting heroin (OR 1.90 [1.11-3.25]) were positively associated with HIV prevalence. There was no association between using a used syringe at last injection and HIV. Having>10 years of education had lower odds of HIV than being illiterate (OR 0.58 [0.35-0.95]). Having a regular sexual partner (OR 0.74 [0.57-0.97]) or paying for sex with the opposite sex (OR = 0.62 [0.45-0.85]) had lower odds of HIV than not. Conversely, PWID paying a man/hijra for sex had higher odds of HIV (OR 1.20 [1.00-1.43]). Receipt of clean needles varied by city of residence (0-97% coverage), whilst PWID with knowledge of HIV service delivery programs had higher odds of receiving clean needles (OR 4.58 [3.50-5.99]). Injecting behaviors were associated with HIV prevalence among PWID, though risks related to paying for sex remain complicated. Geographical variation in access to clean needles suggests potential benefits of more widely spread public health services.

Key MessagesWhat is already known on this topicThe HIV epidemic in Pakistan is concentrated among key populations including people who inject drugs.What this study addsInjecting practices, sexual behaviors, and socio-economic factors are associated with HIV prevalence among people who inject drugs. Access to harm reduction services is varied in Pakistan.How this study might affect research, practice, or policyAccess to clean free needles, as well as service delivery programs, with a broad geographical reach remain important to curb the HIV epidemic among people who inject drugs in Pakistan.

Trends in HIV incidence following scale-up of harm reduction interventions among people who inject drugs in Kachin, Myanmar, 2008-2020: analysis of a retrospective cohort dataset.

Background: People who inject drugs (PWID) in Kachin, Myanmar, have a high HIV prevalence (>40%), but there is no data on incidence. We used HIV testing data from three harm reduction drop-in centres (DIC) in Kachin (2008-2020) to determine HIV incidence trends among PWID and associations with intervention uptake. Methods: Individuals were HIV-tested at first DIC visit and periodically thereafter, during which demographic and risk behaviour data were collected. Two DIC provided opioid agonist therapy (OAT) from 2008. Monthly DIC-level needle/syringe provision (NSP) data was available from 2012. Site-level 6-monthly NSP coverage was denoted low, high, or medium if it was below the lower quartile, above upper quartile, between these quartiles of provision levels over 2012-2020, respectively. HIV incidence was estimated by linking subsequent test records for those initially testing HIV-negative. Associations with HIV incidence were examined using Cox regression. Findings: Follow-up HIV testing data was available for 31.4% (2227) of PWID initially testing HIV-negative, with 444 incident HIV infections during 6266.5 person years (py) of follow-up. Overall HIV incidence was 7.1 per 100 py (95% confidence interval 6.5-7.8), which decreased from 19.3 (13.3-28.2) in 2008-11 to 5.2 per 100 py (4.6-5.9) in 2017-20. In the full PWID incidence dataset after adjustment for various factors, recent (≤6 weeks) injecting (aHR 1.74, 1.35-2.25) and needle sharing (aHR 2.00, 1.48-2.70) were associated with higher incidence, while longer injection careers were associated with reduced incidence (aHR 0.54, 0.34-0.86, for 2-5 yrs vs <2 yrs). In a reduced dataset including data on OAT access and NSP coverage (2012-2020 for two DIC providing OAT), being on OAT during follow-up was associated with reduced HIV incidence (aHR 0.36, 0.27-0.48, compared to never being on OAT) as was high NSP coverage (aHR 0.64, 0.48-0.84, compared to medium syringe coverage). Interpretation: Although HIV incidence is high among PWID in Kachin, data suggests it has decreased since the scale-up in harm reduction interventions. Funding: US NIH, Médecins du Monde.

Incidence of HIV and hepatitis C virus among people who inject drugs, and associations with age and sex or gender: a global systematic review and meta-analysis.

BACKGROUND: Measuring the incidence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID) is key to track progress towards elimination. We aimed to summarise global data on HIV and primary HCV incidence among PWID and associations with age and sex or gender. METHODS: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies among PWID by searching MEDLINE, Embase, and PsycINFO, capturing studies published between Jan 1, 2000, and Dec 12, 2022, with no language or study design restrictions. We contacted authors of identified studies for unpublished or updated data. We included studies that estimated incidence by longitudinally re-testing people at risk of infection or by using assays for recent infection. We pooled incidence and relative risk (RR; young [generally defined as ≤25 years] vs older PWID; women vs men) estimates using random-effects meta-analysis and assessed risk of bias with a modified Newcastle-Ottawa scale. This study is registered with PROSPERO, CRD42020220884. FINDINGS: Our updated search identified 9493 publications, of which 211 were eligible for full-text review. An additional 377 full-text records from our existing database and five records identified through cross-referencing were assessed. Including 28 unpublished records, 125 records met the inclusion criteria. We identified 64 estimates of HIV incidence (30 from high-income countries [HICs] and 34 from low-income or middle-income countries [LMICs]) and 66 estimates of HCV incidence (52 from HICs and 14 from LMICs). 41 (64%) of 64 HIV and 42 (64%) of 66 HCV estimates were from single cities rather than being multi-city or nationwide. Estimates were measured over 1987-2021 for HIV and 1992-2021 for HCV. Pooled HIV incidence was 1·7 per 100 person-years (95% CI 1·3-2·3; I2=98·4%) and pooled HCV incidence was 12·1 per 100 person-years (10·0-14·6; I2=97·2%). Young PWID had a greater risk of HIV (RR 1·5, 95% CI 1·2-1·8; I2=66·9%) and HCV (1·5, 1·3-1·8; I2=70·6%) acquisition than older PWID. Women had a greater risk of HIV (RR 1·4, 95% CI 1·1-1·6; I2=55·3%) and HCV (1·2, 1·1-1·3; I2=43·3%) acquisition than men. For both HIV and HCV, the median risk-of-bias score was 6 (IQR 6-7), indicating moderate risk. INTERPRETATION: Although sparse, available HIV and HCV incidence estimates offer insights into global levels of HIV and HCV transmission among PWID. Intensified efforts are needed to keep track of the HIV and HCV epidemics among PWID and to expand access to age-appropriate and gender-appropriate prevention services that serve young PWID and women who inject drugs. FUNDING: Canadian Institutes of Health Research, Fonds de recherche du Québec-Santé, Canadian Network on Hepatitis C, UK National Institute for Health and Care Research, and WHO.

Modeling the impact of interventions during an outbreak of HIV infection among people who inject drugs in 2012-2013 in Athens, Greece.

BACKGROUND: A large HIV outbreak in People Who Inject Drugs (PWID) occurred in Athens, Greece in 2011-2013. In response, opioid substitution treatment (OST) and needle and syringe programs (NSP) were scaled-up and a seek-test-treat program was introduced in mid-2012. We aim to assess the impact of these interventions. METHODS: A mathematical model of HIV transmission among PWID was calibrated to data available over time (2009-2013) on HIV prevalence, NSP/antiretroviral treatment (ART) coverage and high-risk injection. A combined interventions scenario, including decrease in high-risk injection through linkage to OST and modification of risk behaviours and access to NSP and ART, was compared to a counterfactual scenario (no improvement at the levels of these interventions), with HIV incidence being the main outcome. RESULTS: HIV incidence increased from <0.1 new cases/100 person-years (in 2009) to 11.0 new cases/100 person-years (in 2012). Under both models, a subsequent decline was projected following early 2012, with incidence at the end of 2013 in the combined interventions scenario being lower by 77% compared to the counterfactual. The projected reduction in incidence under the intervention scenario was in agreement with empirical data. HIV prevalence would have escalated to 20.4% (95% CrI: 16.9%, 23.6%) in 2013 under the counterfactual scenario (vs. 16.8% (95% CrI: 11.2%, 23.0%) under the combined interventions scenario). In total, 31.4% of HIV cases (392) were averted over 2012-2013. CONCLUSION: These results underline the importance of high-coverage harm reduction programs and of community-based interventions to rapidly reach PWID most in need.

Methods and indicators to validate country reductions in incidence of hepatitis C virus infection to elimination levels set by WHO.

One of the main goals of the 2016 Global Health Sector Strategy on viral hepatitis is the elimination of hepatitis C virus (HCV) as a public health problem by 2030, defined as an 80% reduction in incidence and 65% reduction in mortality relative to 2015. Although monitoring HCV incidence is key to validating HCV elimination, use of the gold-standard method, which involves prospective HCV retesting of people at risk, can be prohibitively resource-intensive. Additionally, few countries collected quality data in 2015 to enable an 80% decrease by 2030 to be calculated. Here, we first review different methods of monitoring HCV incidence and discuss their resource implications and applicability to various populations. Second, using mathematical models developed for various global settings, we assess whether trends in HCV chronic prevalence or HCV antibody prevalence or scale-up levels for HCV testing, treatment, and preventative interventions can be used as reliable alternative indicators to validate the HCV incidence target. Third, we discuss the advantages and disadvantages of an absolute HCV incidence target and suggest a suitable threshold. Finally, we propose three options that countries can use to validate the HCV incidence target, depending on the available surveillance infrastructure.

Modelling the role of Tax expression in HTLV-I persistence in vivo.

Human T-lymphotropic virus type I (HTLV-I) is a persistent human retrovirus characterized by life-long infection and risk of developing HAM/TSP, a progressive neurological and inflammatory disease, and adult T-cell leukemia (ATL). Chronically infected individuals often harbor high proviral loads despite maintaining a persistently activated immune response. Based on a new hypothesis for the persistence of HTLV-I infection, a three-dimensional compartmental model is constructed that describes the dynamic interactions among latently infected target cells, target-cell activation, and immune responses to HTLV-I, with an emphasis on understanding the role of Tax expression in the persistence of HTLV-I.