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 We contacted authors of identified studies for unpublished or updated data.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 Including 28 unpublished records, 125 records met the inclusion criteria.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

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually

Hepatitis C Elimination in Sweden: Progress, Challenges and Opportunities for Growth in the time of COVID‐19

BACKGROUND & AIMS: In 2014, the burden of hepatitis C virus (HCV) in Sweden was evaluated, to establish a baseline and inform public health interventions. Considering the changing landscape of HCV treatment, prevention, and care, and in light of the COVID‐19 pandemic, this analysis seeks to evaluate Sweden’s progress toward the WHO elimination targets and identify remaining barriers. METHODS: The data used for modeling HCV transmission and disease burden in Sweden were obtained through literature review, unpublished sources, and expert input. A dynamic Markov model was employed to forecast population sizes and incidence of HCV through 2030. Two scenarios (“2019 Base” and “WHO Targets”) were developed to evaluate Sweden’s progress toward HCV elimination. RESULTS: At the beginning of 2019, there were 29,700 (95% UI: 19,300 – 33,700) viremic infections in Sweden. Under the base scenario, Sweden would achieve and exceed the WHO targets for diagnosis, treatment, and liver‐related death. However, new infections would decrease by less than 10%, relative to 2015. Achieving all WHO targets by 2030 would require 1) expanding harm reduction programs to reach more than 90% of PWID and 2) treating 90% of HCV+ PWID engaged in harm reduction programs and ≥7% of PWID not involved in harm reduction programs, annually by 2025. CONCLUSIONS: It is of utmost importance that Sweden, and all countries, find sustainability in HCV programs by broadening the setting and base of providers to provide stability and continuity of care during turbulent times

Univariable associations between a history of incarceration and HIV and HCV prevalence among people who inject drugs across 17 countries in Europe 2006 to 2020 – is the precautionary principle applicable?

Background: People who inject drugs (PWID) are frequently incarcerated, which is associated with multiple negative health outcomes. Aim: We aimed to estimate the associations between a history of incarceration and prevalence of HIV and HCV infection among PWID in Europe. Methods: Aggregate data from PWID recruited in drug services (excluding prison services) or elsewhere in the community were reported by 17 of 30 countries (16 per virus) collaborating in a European drug monitoring system (2006–2020; n = 52,368 HIV+/−; n = 47,268 HCV+/−). Country-specific odds ratios (OR) and prevalence ratios (PR) were calculated from country totals of HIV and HCV antibody status and self-reported life-time incarceration history, and pooled using meta-analyses. Country-specific and overall population attributable risk (PAR) were estimated using pooled PR. Results: Univariable HIV OR ranged between 0.73 and 6.37 (median: 2.1; pooled OR: 1.92; 95% CI: 1.52–2.42). Pooled PR was 1.66 (95% CI 1.38–1.98), giving a PAR of 25.8% (95% CI 16.7–34.0). Univariable anti-HCV OR ranged between 1.06 and 5.04 (median: 2.70; pooled OR: 2.51; 95% CI: 2.17–2.91). Pooled PR was 1.42 (95% CI: 1.28–1.58) and PAR 16.7% (95% CI: 11.8–21.7). Subgroup analyses showed differences in the OR for HCV by geographical region, with lower estimates in southern Europe. Conclusion: In univariable analysis, a history of incarceration was associated with positive HIV and HCV serostatus among PWID in Europe. Applying the precautionary principle would suggest finding alternatives to incarceration of PWID and strengthening health and social services in prison and after release (‘throughcare’)

Univariable associations between a history of incarceration and HIV and HCV prevalence among people who inject drugs across 17 countries in Europe 2006 to 2020 – is the precautionary principle applicable?

Background: People who inject drugs (PWID) are frequently incarcerated, which is associated with multiple negative health outcomes. Aim: We aimed to estimate the associations between a history of incarceration and prevalence of HIV and HCV infection among PWID in Europe. Methods: Aggregate data from PWID recruited in drug services (excluding prison services) or elsewhere in the community were reported by 17 of 30 countries (16 per virus) collaborating in a European drug monitoring system (2006–2020; n=52,368 HIV+/-; n=47,268 HCV+/-). Country-specific odds ratios (OR) and prevalence ratios (PR) were calculated from country totals of HIV and HCV antibody status and self-reported life-time incarceration history, and pooled using meta-analyses. Country-specific and overall population attributable risk (PAR) were estimated using pooled PR. Results: Univariable HIV OR ranged between 0.73 and 6.37 (median: 2.1; pooled OR: 1.92; 95% CI: 1.52–2.42). Pooled PR was 1.66 (95% CI 1.38–1.98), giving a PAR of 25.8% (95% CI 16.7–34.0). Univariable anti-HCV OR ranged between 1.06 and 5.04 (median: 2.70; pooled OR: 2.51; 95% CI: 2.17–2.91). Pooled PR was 1.42 (95% CI: 1.28–1.58) and PAR 16.7% (95% CI: 11.8–21.7). Subgroup analyses showed differences in the OR for HCV by geographical region, with lower estimates in southern Europe. Conclusion: In univariable analysis, a history of incarceration was associated with positive HIV and HCV serostatus among PWID in Europe. Applying the precautionary principle would suggest finding alternatives to incarceration of PWID and strengthening health and social services in prison and after release (‘throughcare’). © 2021 European Centre for Disease Prevention and Control (ECDC). All rights reserved

Homelessness, unstable housing, and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis

Background: People who inject drugs (PWID) are at increased risk for HIV and hepatitis C virus (HCV) infection and also have high levels of homelessness and unstable housing. We assessed whether homelessness or unstable housing is associated with an increased risk of HIV or HCV acquisition among PWID compared with PWID who are not homeless or are stably housed. Methods: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies published between Jan 1, 2000, and June 13, 2017. Using the same strategy as for this existing database, we searched MEDLINE, Embase, and PsycINFO for studies, including conference abstracts, published between June 13, 2017, and Sept 14, 2020, that estimated HIV or HCV incidence, or both, among community-recruited PWID. We only included studies reporting original results without restrictions to study design or language. We contacted authors of studies that reported HIV or HCV incidence, or both, but did not report on an association with homelessness or unstable housing, to request crude data and, where possible, adjusted effect estimates. We extracted effect estimates and pooled data using random-effects meta-analyses to quantify the associations between recent (current or within the past year) homelessness or unstable housing compared with not recent homelessness or unstable housing, and risk of HIV or HCV acquisition. We assessed risk of bias using the Newcastle-Ottawa Scale and between-study heterogeneity using the I2 statistic and p value for heterogeneity. Findings: We identified 14 351 references in our database search, of which 392 were subjected to full-text review alongside 277 studies from our existing database. Of these studies, 55 studies met inclusion criteria. We contacted the authors of 227 studies that reported HIV or HCV incidence in PWID but did not report association with the exposure of interest and obtained 48 unpublished estimates from 21 studies. After removal of duplicate data, we included 37 studies with 70 estimates (26 for HIV; 44 for HCV). Studies originated from 16 countries including in North America, Europe, Australia, east Africa, and Asia. Pooling unadjusted estimates, recent homelessness or unstable housing was associated with an increased risk of acquiring HIV (crude relative risk [cRR] 1·55 [95% CI 1·23–1·95; p=0·0002]; I2= 62·7%; n=17) and HCV (1·65 [1·44–1·90; p<0·0001]; I2= 44·8%; n=28]) among PWID compared with those who were not homeless or were stably housed. Associations for both HIV and HCV persisted when pooling adjusted estimates (adjusted relative risk for HIV: 1·39 [95% CI 1·06–1·84; p=0·019]; I2= 65·5%; n=9; and for HCV: 1·64 [1·43–1·89; p<0·0001]; I2= 9·6%; n=14). For risk of HIV acquisition, the association for unstable housing (cRR 1·82 [1·13–2·95; p=0·014]; n=5) was higher than for homelessness (1·44 [1·13–1·83; p=0·0036]; n=12), whereas no difference was seen between these outcomes for risk of HCV acquisition (1·72 [1·48–1·99; p<0·0001] for unstable housing, 1·66 [1·37–2·00; p<0·0001] for homelessness). Interpretation: Homelessness and unstable housing are associated with increased risk of HIV and HCV acquisition among PWID. Our findings support the development of interventions that simultaneously address homelessness and unstable housing and HIV and HCV transmission in this population. Funding: National Institute for Health Research, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, and Commonwealth Scholarship Commission. © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Homelessness, unstable housing, and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis

Background: People who inject drugs (PWID) are at increased risk for HIV and hepatitis C virus (HCV) infection and also have high levels of homelessness and unstable housing. We assessed whether homelessness or unstable housing is associated with an increased risk of HIV or HCV acquisition among PWID compared with PWID who are not homeless or are stably housed. Methods: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies published between Jan 1, 2000, and June 13, 2017. Using the same strategy as for this existing database, we searched MEDLINE, Embase, and PsycINFO for studies, including conference abstracts, published between June 13, 2017, and Sept 14, 2020, that estimated HIV or HCV incidence, or both, among community-recruited PWID. We only included studies reporting original results without restrictions to study design or language. We contacted authors of studies that reported HIV or HCV incidence, or both, but did not report on an association with homelessness or unstable housing, to request crude data and, where possible, adjusted effect estimates. We extracted effect estimates and pooled data using random-effects meta-analyses to quantify the associations between recent (current or within the past year) homelessness or unstable housing compared with not recent homelessness or unstable housing, and risk of HIV or HCV acquisition. We assessed risk of bias using the Newcastle-Ottawa Scale and between-study heterogeneity using the I2 statistic and p value for heterogeneity. Findings: We identified 14 351 references in our database search, of which 392 were subjected to full-text review alongside 277 studies from our existing database. Of these studies, 55 studies met inclusion criteria. We contacted the authors of 227 studies that reported HIV or HCV incidence in PWID but did not report association with the exposure of interest and obtained 48 unpublished estimates from 21 studies. After removal of duplicate data, we included 37 studies with 70 estimates (26 for HIV; 44 for HCV). Studies originated from 16 countries including in North America, Europe, Australia, east Africa, and Asia. Pooling unadjusted estimates, recent homelessness or unstable housing was associated with an increased risk of acquiring HIV (crude relative risk [cRR] 1·55 [95% CI 1·23–1·95; p=0·0002]; I2= 62·7%; n=17) and HCV (1·65 [1·44–1·90; p<0·0001]; I2= 44·8%; n=28]) among PWID compared with those who were not homeless or were stably housed. Associations for both HIV and HCV persisted when pooling adjusted estimates (adjusted relative risk for HIV: 1·39 [95% CI 1·06–1·84; p=0·019]; I2= 65·5%; n=9; and for HCV: 1·64 [1·43–1·89; p<0·0001]; I2= 9·6%; n=14). For risk of HIV acquisition, the association for unstable housing (cRR 1·82 [1·13–2·95; p=0·014]; n=5) was higher than for homelessness (1·44 [1·13–1·83; p=0·0036]; n=12), whereas no difference was seen between these outcomes for risk of HCV acquisition (1·72 [1·48–1·99; p<0·0001] for unstable housing, 1·66 [1·37–2·00; p<0·0001] for homelessness). Interpretation: Homelessness and unstable housing are associated with increased risk of HIV and HCV acquisition among PWID. Our findings support the development of interventions that simultaneously address homelessness and unstable housing and HIV and HCV transmission in this population. Funding: National Institute for Health Research, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, and Commonwealth Scholarship Commission