Hepatitis B virus DNA and RNA persist in liver after serologic recovery in persons with hepatitis C virus.

After recovery from a hepatitis B virus (HBV) infection, reactivation can occur with immunosuppression; thus, it is assumed that replication competent HBV persists in the liver. We sought to detect persistent HBV from 13 people with spontaneous recovery. We quantified HBV DNA and RNA in core liver biopsies (median 1.72x106 cells) from people who inject drugs (PWID). Among 13 biopsies, 8 (61%) had evidence of HBV DNA or RNA and 5 (38%) had both HBV DNA and RNA. mRNAs derived from cccDNA and integrated HBV DNA. Here, we show prevalent HBV DNA and RNA despite clinical recovery in PWID.

We used a sensitive method to determine the amount of hepatitis B virus DNA or RNA in the livers of 13 individuals who recovered from hepatitis B virus infection. We found viral DNA or RNA in the liver in 61% of individuals despite no detectable virus in blood. Our findings support that eliminating all hepatitis B from the liver is a difficult treatment goal.

Longitudinal patterns of use of stimulants and opioids in the AIDS linked to the IntraVenous experience cohort, 2005-2019.

BACKGROUND: Overdoses involving opioids and stimulants are on the rise, yet few studies have examined longitudinal trends in use of both substances. We sought to describe use and co-use of opioids and stimulants, 2005-2019, in the AIDS Linked to the Intravenous Experience (ALIVE) cohort - a community-based cohort of people with a history of injection drug use living in or near Baltimore, MD. METHODS: We included 2083 ALIVE participants, who had at least two visits during the study period. Our outcome was based on self-reported use of opioids and stimulants in the prior 6 months. We estimated prevalence of 4 categories of use (neither stimulants nor opioids, only stimulants, only opioids, stimulants and opioids), using a non-parametric multi-state model, accounting for the competing event of death and weighting for informative loss to follow-up. All analyses were stratified by enrollment cohort, with the main analysis including participants who enrolled prior to 2015 and a sub-analysis including participants who enrolled 2015-2018. RESULTS: In the main analysis, prevalence of using stimulants and opioids decreased from 38 % in 2005 to 12 % 2013 but stabilized from 2014 onwards (13-19 %). The prevalence of using only stimulants (7-11 %) and only opioids (5-10 %) was stable across time. Participants who reported using both were more likely to report homelessness, depression, and other substance use (e.g., marijuana and heavy alcohol use) than participants in the other use categories. On average, 65 % of visits with use of both were followed by a subsequent visit with use of both; of participants transitioning out of using both, 13% transitioned to using neither. CONCLUSIONS: While use of stimulants and opioids declined in the cohort through 2013, a meaningful proportion of participants persistently used both. More research is needed to understand and develop strategies to mitigate harms associated with persistent use of both stimulants and opioids.

Time-to-completion of COVID-19 vaccination primary series varies by HIV viral load status among people who inject drugs in Baltimore, Maryland.

People who inject drugs (PWID) may have diminished access to essential preventive services like COVID-19 vaccination given structural and substance use barriers. We aimed to assess the role of HIV on COVID-19 vaccination uptake among adult PWID participating in the ALIVE cohort study in Baltimore, Maryland who were alive as of April 2021. We abstracted COVID-19 vaccination data from electronic medical records via the regional health information exchange. We used Kaplan-Meier method to estimate time from universal vaccine eligibility (April 6, 2021) to completion of the COVID-19 vaccination primary series (1 dose J&J or 2 doses mRNA) by HIV viral load status (uninfected, PWH [HIV-RNA < 400 copies/mL], PWH [HIV-RNA ≥ 400 copies/mL]) and Cox Proportional Hazards regression to adjust for potential confounders. Our sample (N = 960) was primarily black (77%) and male (65%) with 31% reporting recent injection drug use. Among 265 (27%) people living with HIV (PWH) in our sample, 84% were virally suppressed. As of February 22, 2022, 539 (56%) completed the primary series, 131 (14%) received a single dose of mRNA vaccine and 290 (30%) remained unvaccinated. Compared to PWID without HIV, virally suppressed PWH were more likely to complete the primary series (Adjusted Hazard Ratio [aHR]:1.23,95% Confidence Interval [95 %CI]:1.07,1.50), while PWH who were not virally suppressed were less likely (aHR:0.72,95 %CI:0.45,1.16), although this was not statistically significant. We conclude that among PWID, HIV infection and viral suppression is associated with quicker vaccination uptake, likely due to HIV care engagement. Targeted improvements along the HIV care continuum may bolster vaccine uptake.

Mitochondrial DNA copy number is associated with incident chronic kidney disease and proteinuria in the AIDS linked to the intravenous experience cohort.

We evaluated the prospective association of mitochondrial DNA copy number (mtDNA CN) with markers of kidney function among a cohort of persons who inject drugs (PWID). This is a Prospective cohort study nested in the AIDS linked to the intravenous experience cohort (community-based cohort of PWID in Baltimore, MD). mtDNA CN was measured at two time-points 5 years apart using a real-time polymerase chain reaction. Kidney function (estimated glomerular filtration rate [eGFR], serum creatinine, urine protein) was measured annually. We used linear mixed effects models to evaluate kidney function trajectories (N = 946) and Cox regression models to assess hazard of incident CKD (eGFR < 60 at two consecutive visits, N = 739) and proteinuria (urine protein:creatinine ratio > 200, N = 573) by level of mtDNA CN (Low [lowest quartile], vs high [other three quartiles]. Models were adjusted for demographic and behavioral characteristics, HIV and/or HCV infection, and comorbidity burden. Low mtDNA CN was independently associated with higher hazard of incident CKD (aHR: 2.33, 95% CI 1.42, 3.80) and proteinuria (aHR: 1.42, 95% CI 1.04, 1.96). Participants with low mtDNA CN had greater declines in eGFR and greater increases in serum creatinine over time. Low mtDNA CN is associated with more rapid kidney function decline and risk of incident CKD and proteinuria.

Prevalence and correlates of SARS-CoV-2 seropositivity among people who inject drugs in Baltimore, Maryland.

Background: SARS-CoV-2 serosurveys can help characterize disparities in SARS-CoV-2 infection and identify gaps in population immunity. Data on SARS-CoV-2 seroprevalence among people who inject drugs (PWID) are limited. Methods: We conducted a cross-sectional study between December 2020 and July 2022 among 561 participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study-a community-based cohort of current and former PWID in Baltimore, Maryland. Serum samples were assayed for infection-induced anti-nucleocapsid (anti-N) and infection and/or vaccination-induced anti-spike-1 (anti-S) SARS-CoV-2 IgG. We estimated adjusted prevalence ratios (aPR) via modified Poisson regression models. Results: The median age was 59 years, 35% were female, 84% were non-Hispanic Black, and 16% reported recent injection drug use. Anti-N antibody prevalence was 26% and anti-S antibody prevalence was 63%. Anti-N and anti-S antibody prevalence increased over time. Being employed (aPR=1.53 [95%CI=1.11-2.11]) was associated with higher anti-N prevalence, while a cancer history (aPR=0.40 [95%CI=0.17-0.90]) was associated with lower anti-N prevalence. HIV infection was associated with higher anti-S prevalence (aPR=1.13 [95%CI=1.02-1.27]), while younger age and experiencing homelessness (aPR=0.78 [95%CI=0.60-0.99]) were factors associated with lower anti-S prevalence. Substance use-related behaviors were not significantly associated with anti-N or anti-S prevalence. Conclusions: SARS-CoV-2 seroprevalence increased over time among current and former PWID, suggesting cumulative increases in the incidence of SARS-CoV-2 infection and vaccination; however, there were disparities in infection-induced seroprevalence and infection and/or vaccine-induced seroprevalence within this study sample. Dedicated prevention and vaccination programs are needed to prevent disparities in infection and gaps in population immunity among PWID during emerging epidemics.

Trajectories of drug treatment and illicit opioid use in the AIDS Linked to the IntraVenous Experience cohort, 2014-2019.

BACKGROUND: Medication for opioid use disorder (MOUD) is an effective intervention to combat opioid use disorder and overdose, yet there is limited understanding of engagement in treatment over time in the community, contextualized by ongoing substance use. We aimed to identify concurrent trajectories of methadone prescriptions, buprenorphine prescriptions, and illicit opioid use among older adults with a history of injection drug use. METHODS: We used data on 887 participants from the AIDS Linked to the IntraVenous Experience cohort, who were engaged in the study in 2013 and attended ≥1 visit during follow-up (2014-2019). Outcomes were self-reported MOUD prescription and illicit opioid use in the last 6 months. To identify concurrent trajectories in all 3 outcomes, we used group-based multi-trajectory modeling. We examined participant characteristics, including sociodemographics, HIV status, and other substance use, overall and by cluster. RESULTS: We identified 4 trajectory clusters: (1) no MOUD and no illicit opioid use (43%); (2) buprenorphine and some illicit opioid use (11%); (3) methadone and no illicit opioid use (28%); and (4) some methadone and illicit opioid use (18%). While prevalence of each outcome was stable across time, transitions on/off treatment or on/off illicit opioid use occurred, with the rate of transition varying by cluster. The rate of transition was highest in Cluster 3 (0.74/person-year) and lowest in Cluster 1 (0.18/person-year). We saw differences in participant characteristics by cluster, including that the buprenorphine cluster had the highest proportion of people with HIV and participants who identified as non-Hispanic Black. CONCLUSIONS: Most participants had discontinued illicit opioid use and were also not accessing MOUD. Trajectories defined by engagement with buprenorphine or methadone had distinct sociodemographic and behavioral characteristics, indicating that tailored interventions to expand access to both types of treatment are likely needed to reduce harms associated with untreated opioid use disorder.

Geographic variation in HCV treatment penetration among people who inject drugs in Baltimore, MD.

We evaluated geographic heterogeneity in hepatitis C virus (HCV) treatment penetration among people who inject drug (PWID) across Baltimore, MD since the advent of direct-acting antivirals (DAAs) using space-time clusters of HCV viraemia. Using data from a community-based cohort of PWID, the AIDS Linked to the IntraVenous Experience (ALIVE) study, we identified space-time clusters with higher-than-expected rates of HCV viraemia between 2015 and 2019 using scan statistics. We used Poisson regression to identify covariates associated with HCV viraemia and used the regression-fitted values to detect adjusted space-time clusters of HCV viraemia in Baltimore city. Overall, in the cohort, HCV viraemia fell from 77% in 2015 to 64%, 49%, 39% and 36% from 2016 to 2019. In Baltimore city, the percentage of census tracts where prevalence of HCV viraemia was ≥85% dropped from 57% to 34%, 25%, 22% and 10% from 2015 to 2019. We identified two clusters of higher-than-expected HCV viraemia in the unadjusted analysis that lasted from 2015 to 2017 in East and West Baltimore and one adjusted cluster of HCV viraemia in West Baltimore from 2015 to 2016. Neither differences in age, sex, race, HIV status, nor neighbourhood deprivation were able to explain the significant space-time clusters. However, residing in a cluster with higher-than-expected viraemia was associated with age, sex, educational attainment and higher levels of neighbourhood deprivation. Nearly 4 years after DAAs became available, HCV treatment has penetrated all PWID communities across Baltimore city. While nearly all census tracts experienced improvements, change was more gradual in areas with higher levels of poverty.

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.

Temporal association of pre-pandemic perceived social support with psychological resilience and mental well-being during the COVID-19 pandemic among people with a history of injection drug use.

BACKGROUND: There are limited data on whether modifiable social factors foster psychological resilience and mental well-being among people who use drugs following Big Events. We examined the temporal association of pre-pandemic perceived social support with psychological resilience and negative mental health symptoms during the COVID-19 pandemic among people with a history of injection drug use. METHODS: Between June and September 2020, we conducted a telephone survey among 545 participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study: a community-based cohort of adults with a history of injection drug use. Leveraging data from study visits in 2018-early 2020, associations of pre-pandemic perceived social support with psychological resilience scores (range=1-5) and the probability of negative mental health symptoms during the pandemic were assessed using multivariable linear and modified Poisson regression models, respectively. RESULTS: Participants' median age was 58 years, 38.2% were female, 83.3% identified as Black, and 30.3% were living with HIV. During the pandemic, 14.5% had low (<3) resilience scores, 36.1% experienced anxiety, and 35.8% reported increased loneliness. Compared to participants in the lowest tertile of pre-pandemic social support, participants in the highest tertile had higher mean resilience scores (ß = 0.27 [95% CI = 0.12, 0.43]), a lower probability of anxiety (prevalence ratio [PR] = 0.71 [95% CI = 0.52, 0.96]), and a lower probability of increased loneliness (PR = 0.62 [95% CI = 0.45, 0.84]). CONCLUSIONS: Pre-pandemic perceived social support was associated with greater psychological resilience and generally better mental well-being during the pandemic. Interventions that improve social support may foster psychological resilience and protect the mental well-being of people who use drugs, especially during periods of social disruption.

Temporal trends in HCV treatment uptake and success among people who inject drugs in Baltimore, MD since the introduction of direct acting antivirals.

Background: Although hepatitis C virus (HCV) can be cured by direct acting antivirals (DAA), uptake is not well characterized for people who inject drugs (PWID). Methods: Among 1,130 participants of a community-based cohort of PWID with chronic HCV, we longitudinally characterized HCV treatment uptake and cure early (2014-2016) and later (2017-2020). Results: Cumulative HCV treatment uptake increased from 4% in 2014 to 68% in 2020 and the percent with HCV viremia declined from nearly 100% to 33%. Predictors of treatment uptake varied across periods. Age (incidence rate ratio [IRR] per 5-year increase: 1.28; 95% confidence interval [CI]: 1.15, 1.42), educational attainment (IRR for ≥ high school diploma: 1.31; 95% CI: 1.04, 1.66), HIV coinfection with suppressed viral load (IRR vs. HIV negative: 2.08; 95% CI: 1.63, 2.66) and alcohol dependence (IRR vs. no alcohol use: 0.63; 95% CI: 0.43, 0.91) were associated with treatment uptake in the early period, but not later. HIV coinfection with a detectable viral load (IRR vs. HIV negative: 0.46; 95% CI: 0.23, 0.95) and daily injecting (IRR: 0.46 vs. no injection; 95% CI: 0.27, 0.79) were significantly associated with lower treatment uptake later. Homelessness was associated with significantly reduced likelihood of viral clearance in the late DAA era (IRR: 0.51; 95% CI: 0.30, 0.88). Conclusion: Treatment uptake improved substantially in this cohort of PWID in the first five years of DAA availability with commensurate declines in viremia. Additional efforts are needed to treat those actively injecting and unstably housed in order to realize elimination goals.

Mortality by cause of death during year 1 of the COVID-19 pandemic in a cohort of older adults from Baltimore Maryland who have injected drugs.

BACKGROUND: In 2020, the first year of the COVID-19 pandemic, overdose deaths increased. However, no studies have characterized changes in mortality during the pandemic in a well-characterized cohort of people who use drugs in active follow-up at the time of pandemic onset. DESIGN: We compared all-cause and cause-specific mortality in the first year of the pandemic (Mar-Dec 2020) to the five years preceding (Jan 2015-Feb 2020), among participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study: a community-recruited cohort of adults from Baltimore who have injected drugs. 3510 participants contributed 17,498 person-years [py] of follow-up time. Cause and dates of death were ascertained through the National Death Index. Comparisons were made for the full cohort and within subgroups with potentially differential levels of vulnerability. RESULTS: All-cause mortality in 2020 was 39.6 per 1000 py, as compared to 37.2 per 1000 py pre- pandemic (Adjusted Incidence Rate Ratio = 1.09, 95%: confidence interval: 0.84-1.41). Increases were mostly attributable to chronic disease deaths; injury/poisoning deaths did not increase. No pre-post differences were statistically significant. CONCLUSION: In this exploratory analysis of an older cohort of urban-dwelling adults who have injected drugs, mortality changes during the first year of the pandemic differed from national trends and varied across potentially vulnerable subgroups. More research is needed to understand determinants of increased risk of mortality during the pandemic among subgroups of people who use drugs.

Adverse childhood experiences and comorbidity in a cohort of people who have injected drugs.

BACKGROUND: Childhood adversity is associated with the onset of harmful adult substance use and related health problems, but most research on adversity has been conducted in general population samples. This study describes the prevalence of adverse childhood experiences in a cohort of people who have injected drugs and examines the association of these adverse experiences with medical comorbidities in adulthood. METHODS: Six hundred fifty three adults were recruited from a 30-year cohort study on the health of people who have injected drugs living in and around Baltimore, Maryland (Median age = 47.5, Interquartile Range = 42.3-52.3 years; 67.3% male, 81.1% Black). Adverse childhood experiences were assessed retrospectively in 2018 via self-report interview. Lifetime medical comorbidities were ascertained via self-report of a provider diagnosis. Multinomial logistic regression with generalized estimating equations was used to examine the association between adversity and comorbid conditions, controlling for potential confounders. RESULTS: Two hundred twelve participants (32.9%) reported 0-1 adverse childhood experiences, 215 (33.3%) reported 2-4, 145 (22.5%) reported 5-9, and 72 (11.1%) reported ≥10. Neighborhood violence was the most commonly reported adversity (48.5%). Individuals with ≥10 adverse childhood experiences had higher odds for reporting ≥3 comorbidities (Adjusted Odds Ratio = 2.9, 95% CI = 1.2 - 6.8, p = .01). CONCLUSIONS: Among people who have injected drugs, adverse childhood experiences were common and associated with increased occurrence of self-reported medical comorbidities. Findings highlight the persistent importance of adversity for physical health even in a population where all members have used drugs and there is a high burden of comorbidity.

Epigenome-wide association analyses of active injection drug use.

BACKGROUND: Injection drug use (IDU) is prevalent in the US and is associated with substantial risk of blood-borne infections, morbidity, and mortality. However, the spectrum of its biologic effects on DNA methylation in blood is not well characterized. METHODS: 401 participants (Mage = 47.9; 68% male; 90% African American) over several timepoints (1054 visits) were drawn from a longitudinal cohort of people who inject drugs. DNA methylation was measured among buffy coat samples from the 1054 visits. Compared to samples collected after ≥ 6 months of abstinence, separate EWAS were conducted for active injecting of any drug, quantitative injection frequency, injecting of heroin and injecting of cocaine. Linear mixed effect models were used and analyses were adjusted for repeated measurements and key technical, biological, and sociodemographic characteristics. RESULTS: We found epigenome-wide significant CpG sites associated with active injection (cg10636246, AIM2, p = 2.33 × 10-8) and injection intensity (cg13117953, p = 4.30 × 10-8). We found converging evidence that cg10636246 (AIM2), cg23110600 (PRKCH), cg03546163 (FKBP5), cg04590956 (GMCL1), and cg16317961 (MAPRE2) were among the top 0.1% significantly differentially methylated CpG sites shared across the five EWAS. Top ranked CpGs among the five EWAS were enriched (p < 0.0001) in AIM2 inflammasome complex, T cell migration, insulin regulation and epinephrine synthesis pathways. During periods of active injection, samples had 0.46 years of epigenetic age acceleration relative to the abstinence period, within the same subject (p = 0.03). CONCLUSIONS: Findings from this study demonstrate modest, common, and specific effects on DNA methylation during a relatively short time between periods of active drug injection and abstinence.

SHBG, Bone Mineral Density, and Physical Function Among Injection Drug Users With and Without HIV and HCV.

CONTEXT: Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates the bioavailability of sex hormones and is higher in people with HIV (PWH) and hepatitis C virus (HCV). SHBG is associated with aging-related diseases, including osteoporosis and frailty in the general population. However, the relationship between SHBG concentration and bone mineral density (BMD) and physical function among PWH and HCV is unclear. OBJECTIVE: This study aimed to evaluate the association between chronic infection with HIV and HCV and SHBG, and to assess the relationship of circulating SHBG concentrations with low BMD, physical function impairment, and frailty. METHODS: A cross-sectional study was conducted of 278 HCV-exposed (HCV antibody positive) adults enrolled with and without HIV and HCV from the AIDS Linked to the IntraVenous Experience cohort study into 4 groups: HCV-/HIV-, HCV-/HIV+, HCV+/HIV-, and HCV+/HIV+. We evaluated the association between SHBG concentrations and grip strength, gait speed, Short Physical Performance Battery score, frailty (Fried Frailty Phenotype), and BMD (lumbar spine, total hip, and femoral neck T-score) by using adjusted multivariable regression stratified by sex. RESULTS: SHBG concentrations were higher in women, in those with HIV RNA greater than 400 copies/mL (P = .02) and HCV RNA greater than 15 IU/mL (P < .001). In adjusted models, higher SHBG concentrations among women were statistically significantly associated with lower grip strength (-0.43 [95% CI, -0.77 to -0.081] kg/10 nmol/L, P < .05), higher odds of frailty (odds ratio, 1.49 [95% CI, 1.07 to 2.08], P < .05), and lower T-scores at the lumbar spine (-0.070 [95% CI, -0.15 to -0.001] SD/10 nmol/L T-score BMD, P < .05). Similar associations were not observed among men. CONCLUSION: Higher SHBG concentrations are associated with the presence of HIV and HCV viremia. Among women, but not men, higher SHBG concentrations were associated with lower grip strength, higher odds of frailty, and lower lumbar spine BMD. The underlying mechanisms of these associations require further investigation.

Brief Report: HIV Is Associated With Impaired Pulmonary Diffusing Capacity Independent of Emphysema.

BACKGROUND: HIV is associated with accelerated decline in lung function and increased risk for chronic obstructive pulmonary disease (COPD). Recently, there has been growing attention toward the impairment in the diffusing capacity of the lungs for carbon monoxide (DLCO), a marker of pulmonary gas exchange, observed among persons living with HIV. Although increased emphysema can contribute to the DLCO impairment observed, other factors may drive this association. METHODS: Using cross-sectional data from the Study of HIV in the Etiology of Lung Disease, we studied the association between HIV and DLCO independent of emphysema. We also analyzed the joint influence of HIV and COPD on DLCO impairment. An analysis was conducted among 339 participants (229 with HIV) with lung function and chest CT imaging data. Multivariable regression models were generated with percent predicted DLCO and odds of DLCO impairment as outcomes. RESULTS: After adjusting for confounders, including emphysema severity, HIV was associated with lower DLCO (ß -4.02%; P = 0.020) and higher odds of DLCO impairment (odds ratio 1.93; P = 0.017). Even among those without COPD, HIV was independently associated with lower DLCO (ß -3.89%; P = 0.049). Compared with HIV-uninfected participants without COPD, those with both HIV and COPD experienced the greatest impairment in DLCO (ß -14.81; P < 0.001). CONCLUSIONS: HIV is associated with impaired pulmonary gas exchange independent of emphysema severity. Our data also suggest a potentially additive influence between HIV and COPD on DLCO impairment. Further studies should investigate the other factors, including pulmonary vascular disease, which may contribute to DLCO impairment among persons living with HIV.

Mortality among people who inject drugs: a prospective cohort followed over three decades in Baltimore, MD, USA.

BACKGROUND AND AIMS: During the past decades, people who inject drugs (PWID) have been impacted by the development of combination antiretroviral therapy (cART) to combat HIV/AIDS, the prescription opioid crisis and increased use of lethal synthetic opioids. We measured how these dynamics have impacted mortality among PWID in an urban US city. DESIGN: Prospective cohort study using data from the AIDS Linked to the Intravenous Experience (ALIVE). SETTING: Baltimore, MD, USA from 1988 to 2018. PARTICIPANTS: A total of 5506 adult PWIDs (median age at baseline 37 years). MEASUREMENTS: Mortality was identified by linkage to National Death Index-Plus (NDI-Plus) and categorized into HIV/infectious disease (HIV/ID) deaths, overdose and violence-related (drug-related) deaths and chronic disease deaths. Person-time at risk accrued from baseline and ended at the earliest of death or study period. All-cause and cause-specific mortality were calculated annually. The Fine & Gray method was used to estimate the subdistribution hazards of cause-specific deaths accounting for competing risks. FINDINGS: Among 5506 participants with 84 226 person-years of follow-up, 43.9% were deceased by 2018. Among all deaths, 30.5% were HIV/ID deaths, 24.4% drug-related deaths and 33.3% chronic disease deaths. Age-standardized all-cause mortality increased from 23 to 45 per 1000 person-years from 1988 to 1996, declined from 1996 to 2014, then trended upward to 2018. HIV/ID deaths peaked in 1996 coincident with the availability of cART, then continuously declined. Chronic disease deaths increased continuously as the cohort aged. Drug-related deaths declined until 2011, but increased more than fourfold by 2018. HIV/HCV infection and active injecting were independently associated with HIV/ID and drug-related deaths. Female and black participants had a higher risk of dying from HIV/ID deaths and a lower risk of dying from drug-related deaths than male and non-black participants. CONCLUSIONS: Deaths in Baltimore, MD, USA attributable to HIV/ID appear to have declined following the widespread use of combination antiretroviral therapy. Increases in the rates of drug-related deaths in Baltimore were observed prior to and continue in conjunction with national mortality rates associated with the opiate crisis.

Trends in fatal and nonfatal overdose by race among people who inject drugs in Baltimore, Maryland from 1998 to 2019.

OBJECTIVE: The objective of this study was to examine trends in fatal and nonfatal overdose in a community-based sample of current and former people who inject drugs (PWID). METHODS: Data from 4826 current and former PWID from the AIDS Linked to the IntraVenous Experience (ALIVE) observational cohort study in Baltimore, Maryland, were used to characterize fatal and nonfatal overdose rates from 1998 to 2019. Poisson regression was used to examine factors associated with nonfatal overdose and differences by race among 1052 PWID between 2014 and 2019. RESULTS: Fatal overdose rates reached a high of 13 per 1000 person-years in 2018. Among 1052 current and former PWID, of whom 75% were Black and one-third were female, the nonfatal overdose rate of 529 per 1000 person-years in 2019 was 8 times higher than 2014 (incidence rate ratio [IRR]=7.76, 95% CI: 3.35, 18.0). The annual adjusted increase in nonfatal overdose rate was 53% among Black PWID (IRR=1.53, 95% CI: 1.34, 1.75), compared to 14% among White PWID (IRR=1.14, 95% CI: 0.88, 1.46). Urban residence, opioid use, depressive symptoms, and hepatitis C infection were positively associated with nonfatal overdose among Black PWID. Recent injection drug use and tranquilizer use was associated with increased overdose among Black and White PWID. CONCLUSIONS: Rates of fatal and nonfatal overdose were high and increased from 2014 to 2019 among current and former PWID, with the most dramatic increases in nonfatal overdose observed among Black PWID. These findings highlight the urgent need for additional resources to reduce the differential harms associated with opioids by race.

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.

The health and social consequences during the initial period of the COVID-19 pandemic among current and former people who inject drugs: A rapid phone survey in Baltimore, Maryland.

BACKGROUND: There is limited data on the health and social consequences of the COVID-19 pandemic among people who inject drugs (PWID). METHODS: We conducted a rapid telephone survey from April-June 2020 among participants of the community-based AIDS Linked to the IntraVenous Experience (ALIVE) cohort study in Baltimore, Maryland. This interviewer-administered survey collected information on COVID-19 knowledge, symptoms, testing, diagnosis, and prevention behaviors, recent substance use, housing conditions, interruptions to healthcare, access to harm reduction and drug treatment, mental health, and social support. RESULTS: Of 443 current and former PWID who participated in the survey, 36 % were female, 85 % were Black, 33 % were living with HIV and 50 % reported any substance use in the prior six months. COVID-19 awareness was high, but knowledge of symptoms and routes of transmission were lower. PWID reporting recent substance use were less likely to always socially distance (63 % vs. 74 % among those without recent use, p = 0.02), and Black PWID were more likely than non-Black to socially distance (73 % vs. 48 %, p < 0.0001) and use when alone (68 % vs.35 %, p < 0.01). Only 6% reported difficulty accessing healthcare, yet only 48 % of those on opioid-agonist treatment had a four-week supply available. While 34 % reported increased depressive symptoms, participants reported high levels of social support. CONCLUSIONS: This rapid assessment highlighted that PWID currently using drugs may be less able to practice social distancing and increased SARS-CoV-2 transmission may occur. Ongoing monitoring of substance use and mental health, as well as overdose prevention is necessary as the pandemic and public health responses continue.

Epigenome-wide association scan identifies methylation sites associated with HIV infection.

Aim: To investigate the role of epigenetics in HIV pathophysiology. Materials & methods: We conducted an epigenome-wide association scan on HIV infection status among people who inject drugs in the AIDS Linked to the IntraVenous Experience study with primary (n = 397) and validation samples (n = 390). DNA methylation from blood was measured by the Illumina EPIC BeadChip. We controlled for cell type heterogeneity by HIV status. Results: HIV infection status was associated (p < 10-8) with DNA methylation at 49 CpG sites. Sites were enriched in response to virus, interferon signaling pathway, etc. Among these sites, discovery and validation t-statistics were highly correlated (r = 0.96). Conclusion: In a cohort of people who inject drugs, HIV status was associated with differential DNA methylation at biologically meaningful sites.