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 We contacted authors of identified studies for unpublished or updated data.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 Including 28 unpublished records, 125 records met the inclusion criteria.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; I 2=98·4%) and pooled HCV incidence was 12·1 per 100 person-years (10·0-14·6; I 2=97·2%). Young PWID had a greater risk of HIV (RR 1·5, 95% CI 1·2-1·8; I 2=66·9%) and HCV (1·5, 1·3-1·8; I 2=70·6%) acquisition than older PWID. Women had a greater risk of HIV (RR 1·4, 95% CI 1·1-1·6; I 2=55·3%) and HCV (1·2, 1·1-1·3; I 2=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.</p

Progression of Biopsy-Measured Liver Fibrosis in Untreated Patients with Hepatitis C Infection: Non-Markov Multistate Model Analysis

BACKGROUND: Fibrosis stages from liver biopsies reflect liver damage from hepatitis C infection, but analysis is challenging due to their ordered but non-numeric nature, infrequent measurement, misclassification, and unknown infection times. METHODS: We used a non-Markov multistate model, accounting for misclassification, with multiple imputation of unknown infection times, applied to 1062 participants of whom 159 had multiple biopsies. Odds ratios (OR) quantified the estimated effects of covariates on progression risk at any given time. RESULTS: Models estimated that progression risk decreased the more time participants had already spent in the current stage, African American race was protective (OR 0.75, 95% confidence interval 0.60 to 0.95, p = 0.018), and older current age increased risk (OR 1.33 per decade, 95% confidence interval 1.15 to 1.54, p = 0.0002). When controlled for current age, older age at infection did not appear to increase risk (OR 0.92 per decade, 95% confidence interval 0.47 to 1.79, p = 0.80). There was a suggestion that co-infection with human immunodeficiency virus increased risk of progression in the era of highly active antiretroviral treatment beginning in 1996 (OR 2.1, 95% confidence interval 0.97 to 4.4, p = 0.059). Other examined risk factors may influence progression risk, but evidence for or against this was weak due to wide confidence intervals. The main results were essentially unchanged using different assumed misclassification rates or imputation of age of infection. DISCUSSION: The analysis avoided problems inherent in simpler methods, supported the previously suspected protective effect of African American race, and suggested that current age rather than age of infection increases risk. Decreasing risk of progression with longer time already spent in a stage was also previously found for post-transplant progression. This could reflect varying disease activity, with recent progression indicating active disease and high risk, while longer time already spent in a stage indicates quiescent disease and low risk

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

Epistatic Effects of Immunoglobulin GM and KM Allotypes on Outcome of Infection with Hepatitis C Virus

Immunoglobulin GM and KM allotypes—genetic markers of γ and κ chains, respectively—are associated with immune responsiveness to several infectious pathogens and with survival in certain viral epidemics. We hypothesized that GM and KM allotypes affect the outcome of hepatitis C virus (HCV) infection. To test this hypothesis, we serologically allotyped 100 persons with well-documented clearance of HCV infection and 198 matched persistently infected persons. None of the GM or KM phenotypes by itself was associated with the clearance or persistence of HCV infection. Particular combinations of these phenotypes, however, were significantly associated with the outcome of HCV infection. Subjects with GM 1,17 5,13 and KM 1,3 phenotypes were over three times (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.44 to 8.87) as likely to clear the infection as the subjects who lacked these phenotypes. This GM phenotype had a similar association with clearance in the absence of KM 3 (OR, 2.75; 95% CI, 1.21 to 6.23). The presence of GM 1,3,17 23 5,13 phenotype (in the absence of KM 3) was associated with persistence (OR, 0.21; 95% CI, 0.06 to 0.77), while its absence (in the presence of KM 1,3) was associated with the clearance of infection (OR, 2.03; 95% CI, 1.16 to 3.54). These results show epistatic interactions of genes on chromosomes 14 (GM) and 2 (KM) in influencing the outcome of an HCV infection. Further investigations involving candidate genes (GM, KM, HLA, and Fcγ receptors) and cellular and humoral immune responses to HCV epitopes are needed to understand the mechanisms underlying these associations

Incarceration and injection drug use in Baltimore, Maryland

AimsThere is limited longitudinal research examining incarceration and subsequent changes in drug use among people who inject drugs (PWID) in the United States. The objective of the current study was to characterize the frequency of incarceration and estimate the association between incarceration and subsequent injection drug use among current and former PWIDs in one US city.DesignALIVE (AIDS Linked to the Intravenous Experience) is a prospective cohort study of current and former PWIDs, with semi-annual follow-up occurring since 1988.SettingBaltimore, Maryland, USA.ParticipantsA total of 3245 participants with 48 738 study visits were included. Participants enrolled from 1988 to 2012 with a median of 13 follow-up visits per participant (Interquartile range = 7-25).MeasurementsIncarcerations were defined as any self-reported jail or prison stays in the previous 6 months that were ≥7 days or longer. The primary outcome was defined as any self-reported injection drug use in the previous 6 months.FindingsAt baseline, 29% were female, 90% African American and 33% HIV-positive. Fifty-seven per cent of participants experienced at least one incarceration episode. After adjusting for confounders, there was a positive association between incarceration and subsequent injection drug use [adjusted odds ratio (AOR) = 1.48, 95% confidence interval (CI) = 1.37-1.59]; however, stratified analysis showed that the effect was restricted to those who were not injecting at the time of incarceration (AOR = 2.11, 95% CI = 1.88-2.37).ConclusionsIn the United States, incarceration of people who had previously stopped injecting drugs appears to be associated with an increased risk of subsequent injecting

Fatal overdose prevention and experience with naloxone: A cross-sectional study from a community-based cohort of people who inject drugs in Baltimore, Maryland.

INTRODUCTION:Overdose is a leading cause of death in the United States, especially among people who inject drugs (PWID). Improving naloxone access and carrying among PWID may offset recent increases in overdose mortality associated with the influx of synthetic opioids in the drug market. This study characterized prevalence and correlates of several naloxone outcomes among PWID. METHODS:During 2018, a survey to assess experience with naloxone was administered to 915 participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study, an ongoing community-based observational cohort of people who currently inject or formerly injected drugs in Baltimore, Maryland. We examined the associations of naloxone outcomes (training, supply, use, and regular possession) with socio-demographic, substance use and healthcare utilization factors among PWID in order to characterize gaps in naloxone implementation among this high-risk population. RESULTS:Median age was 56 years, 34% were female, 85% were African American, and 31% recently injected. In the past six months, 46% (n = 421) reported receiving training in overdose prevention, 38% (n = 346) had received a supply of naloxone, 9% (n = 85) had administered naloxone, and 9% (n = 82) reported usually carrying a supply of naloxone. Recent non-fatal overdose was not associated with any naloxone outcomes in adjusted analysis. Active opioid use (aOR = 2.10, 95% CI: 1.03, 4.28) and recent treatment of alcohol or substance use disorder (aOR = 2.01, 95% CI: 1.13, 3.56) were associated with regularly carrying naloxone. CONCLUSION:Further work is needed to encourage PWID to carry and effectively use naloxone to decrease rates of fatal opioid overdose. While accessing treatment for substance use disorder was positively associated with carrying naloxone, EMS response to 911 calls for overdose, the emergency department, and syringe services programs may be settings in which naloxone access and carrying could be encouraged among PWID