An Analysis of Social Determinants of Health and Their Implications for Hepatitis C Virus Treatment in People Who Inject Drugs: The Case of Baltimore.

Background: Sixty-eight percent of the nearly 3.5 million people living with hepatitis C virus (HCV) in the United States are people who inject drugs (PWID). Despite effective treatments, uptake remains low in PWID. We examined the social determinants of health (SDoH) that affect the HCV care cascade. Methods: We conducted a secondary analysis of data from 720 PWID in a cluster-randomized trial. We recruited PWID from 12 drug-affected areas in Baltimore. Inclusion criteria were injection in the prior month or needle sharing in the past 6 months. Intake data consisted of a survey and HCV testing. Focusing on SDoH, we analyzed self-report of (1) awareness of HCV infection (in those with active or previously cured HCV) and (2) prior HCV treatment (in the aware subgroup). We used descriptive statistics and logistic regression for statistical analyses. Results: The 342 participants were majority male and Black with a median age of 52 years. Women were more likely to be aware of their status but less likely to be treated. Having a primary care provider and HIV-positive status were associated with increased awareness and treatment. Unhoused people had 51% lower odds of HCV treatment. People who reported that other PWID had shared their HCV status with them had 2.3-fold higher odds of awareness of their own status. Conclusions: Further study of gender disparities in HCV treatment access is needed. Increased social support was associated with higher odds of HCV treatment, suggesting an area for future interventions. Strategies to identify and address SDoH are needed to end HCV.

Injection network drivers of HIV prevention service utilization among people who inject drugs: results of a community-based sociometric network cohort in New Delhi, India.

INTRODUCTION: Injection drug networks may influence their network members' health-seeking behaviours. Using data from a sociometric injecting partner network of people who inject drugs (PWID) in New Delhi, India, we assessed the role of injecting partner (alter) behaviours on individual engagement in HIV prevention services. METHODS: We enumerated injecting partner linkages among 2512 PWID using coupon referrals and biometric data from November 2017 to March 2020. Participants completed interviewer-administered questionnaires and provided information on injection behaviours, injecting partners, HIV/hepatitis C (HCV) testing and service engagement. Multilevel multiple-membership models (MMMM) evaluated individual PWID HIV testing, medication for opioid use disorder (MOUD) and syringe service engagement as a function of alter attributes, accounting for membership across multiple ego-networks. Logistic regression models assessed parallel associations among socially proximal injecting peers, defined as PWID ≤3 path length from ego. RESULTS: Median age was 26 years; 99% were male. PWID had median 2 injecting partners and 8 socially proximal peers; 14% reported HIV testing, 33% accessed MOUD and 13% used syringe services 6 months prior. In MMMM analyses, PWID with ≥1 versus 0 injecting partners who received HIV testing were significantly more likely to report HIV testing (adjusted odds ratio [aOR]: 2.27, 95% confidence interval [CI]: 1.68-3.16), MOUD (aOR: 1.99, 95% CI: 1.60-2.53) and syringe service use (aOR: 1.66, 95% CI: 1.21-2.39). We observed similar findings for individual MOUD and syringe service use. Having ≥1 versus 0 HIV-positive partners was associated with decreased HIV testing and MOUD but increased syringe service use (aOR: 1.54, 95% CI: 1.09-2.17). PWID with ≥1 versus 0 socially proximal peers who used non-sterile injection equipment reported increased HIV testing (aOR: 1.39, 95% CI: 1.01-1.92), MOUD (aOR: 1.40, 95% CI: 1.10-1.77) and syringe service use (aOR: 1.82, 95% CI: 1.23-2.68). CONCLUSIONS: We found differential associative relationships between individual HIV prevention service engagement and the health or risk behaviours of direct and indirect alters. Characterizing network exposure beyond direct injecting partnerships provided important context on possible mechanisms of behavioural influence. Findings could be leveraged to design peer-based interventions that promote network diffusion of health-seeking behaviours.

Integrated care van delivery of evidence-based services for people who inject drugs: A cluster-randomized trial.

BACKGROUND AND AIMS: People who inject drugs (PWID) are at risk for adverse outcomes across multiple dimensions. While evidence-based interventions are available, services are often fragmented and difficult to access. We measured the effectiveness of an integrated care van (ICV) that offered services for PWID. DESIGN, SETTING AND PARTICIPANTS: This was a cluster-randomized trial, which took place in Baltimore, MD, USA. Prior to randomization, we used a research van to recruit PWID cohorts from 12 Baltimore neighborhoods (sites), currently served by the city's mobile needle exchange program. INTERVENTION AND COMPARATOR: We randomized sites to receive weekly visits from the ICV (n = 6) or to usual services (n = 6) for 14 months. The ICV offered case management; buprenorphine/naloxone; screening for HIV, hepatitis C virus and sexually transmitted infections; HIV pre-exposure prophylaxis; and wound care. MEASUREMENTS: The primary outcome was a composite harm mitigation score that captured access to evidence-based services, risk behaviors and adverse health events (range = 0-15, with higher numbers indicating worse status). We evaluated effectiveness by comparing changes in the composite score at 7 months versus baseline in the two study arms. FINDINGS: We enrolled 720 cohort participants across the study sites (60 per site) between June 2018 and August 2019: 38.3% women, 72.6% black and 85.1% urine drug test positive for fentanyl. Over a median of 10.4 months, the ICV provided services to 734 unique clients (who may or may not have been cohort participants) across the six intervention sites, including HIV/hepatitis C virus testing in 577 (78.6%) and buprenorphine/naloxone initiation in 540 (74%). However, only 52 (7.2%) of cohort participants received services on the ICV. The average composite score decreased at 7 months relative to baseline, with no significant difference in the change between ICV and usual services (difference in differences: -0.31; 95% confidence interval: -0.70, 0.08; P = 0.13). CONCLUSIONS: This cluster-randomized trial in Baltimore, MD, USA, found no evidence that weekly neighborhood visits from a mobile health van providing injection-drug-focused services improved access to services and outcomes among people who injected drugs in the neighborhood, relative to usual services. The van successfully served large numbers of clients but unexpectedly low use of the van by cohort participants limited the ability to detect meaningful differences.

Network centrality and HIV prevention service use among people who inject drugs: Findings from a sociometric network cohort in New Delhi, India.

BACKGROUND AND AIMS: Network centrality, an indicator of an individual's importance and potential to drive behavioral change, is rarely used to select peer educators. Individual-level predictors of network centrality might be useful to identify people who inject drugs (PWID) for potential roles as peer navigators or change agents in network-based interventions in settings where sociometric data are unavailable. We assessed the relationship between network centrality and HIV prevention service engagement to determine whether centrally-positioned PWID share measurable commonalities. DESIGN: Observational study and survey using baseline data from a sociometric network cohort of PWID, enumerated using network software and biometric data (2017-2020). Network ties corresponded to direct injection partnerships in the prior month. SETTING: New Delhi, India. PARTICIPANTS: A total of 2512 PWID who were ≥18 years, provided written informed consent, and reported illicit injection drug use within the 24 months before study enrollment. MEASUREMENTS: Interviewer-administered questionnaires measured demographics and substance use behaviors. Central versus peripheral network position was categorized using betweenness centrality 75th%ile . Logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals (95%CI) between network position and HIV testing, medication for opioid use disorder (MOUD), or syringe service use. Lasso models selected predictors of central network position among 20 covariates detailing demographic, biologic, and substance use information. Predictive accuracy was evaluated using model performance metrics. FINDINGS: Overall, median age was 26 years (interquartile range 22-34); 99% were male; 628 were classified as central. Compared with PWID at the periphery, central PWID were more likely to use MOUD (aOR: 1.59, 95%CI: 1.30-1.94) and syringe services (aOR: 2.91, 95%CI: 2.25, 3.76) in the prior six months. Findings for HIV testing were inconclusive (aOR: 1.30, 95%CI: 1.00-1.69). The lasso variable selector identified several predictors of network centrality: HIV and hepatitis C infection, number of PWID seen in the prior month, injecting heroin and buprenorphine (vs. heroin only) six months prior, sharing injection equipment six months prior, experiencing drug overdose in the past year, and moderate/severe depression (vs. none/mild). Average agreement between model-predicted vs. observed values was 0.75; area under the receiver operator curve was 0.69. CONCLUSIONS: In a socioeconomic network of people who inject drugs (PWID) in New Delhi, India, there are common characteristics among individuals based on their network position (central vs. peripheral) but individual-level predictors have only moderate predictive accuracy. Although central network members appear to be more likely to use HIV prevention services than peripheral network members, their potential as change agents may be limited by other factors that impede their ability to adopt or promote HIV prevention service use.

Deep learning and social network analysis elucidate drivers of HIV transmission in a high-incidence cohort of people who inject drugs.

Globally, people who inject drugs (PWID) experience some of the fastest-growing HIV epidemics. Network-based approaches represent a powerful tool for understanding and combating these epidemics; however, detailed social network studies are limited and pose analytical challenges. We collected longitudinal social (injection partners) and spatial (injection venues) network information from 2512 PWID in New Delhi, India. We leveraged network analysis and graph neural networks (GNNs) to uncover factors associated with HIV transmission and identify optimal intervention delivery points. Longitudinal HIV incidence was 21.3 per 100 person-years. Overlapping community detection using GNNs revealed seven communities, with HIV incidence concentrated within one community. The injection venue most strongly associated with incidence was found to overlap six of the seven communities, suggesting that an intervention deployed at this one location could reach the majority of the sample. These findings highlight the utility of network analysis and deep learning in HIV program design.

Awareness, perception and utilization of a mobile health clinic by people who use drugs.

INTRODUCTION: People who use drugs (PWUD) face a multitude of barriers to accessing healthcare and other services. Mobile health clinics (MHC) are an innovative, cost-effective health care delivery approach that increases healthcare access to vulnerable populations and medically underserved areas. There is limited understanding, however, of how PWUD perceive and experience MHCs. METHODS: Semi-structured interviews were conducted with 31 PWUD - 16 who had received care (clients) on an MHC (The Spot) and 15 who had not (non-clients) - to explore their perceptions and utilization of an MHC partnered with a mobile syringe services program in Baltimore, Maryland. Data analysis of the text was conducted using an iterative thematic constant comparison process informed by grounded theory. RESULTS: Clients and non-clients, once aware of the MHC, had positive perceptions of The Spot and its benefits for their individual health as well as for the wellbeing of their community. These sentiments among clients were largely driven by access to low-barrier buprenorphine and service delivery without stigma around drug use. However, lack of general awareness of the spot and specific service offering were barriers to its use among non-clients. DISCUSSION: MHCs provide an important opportunity to engage PWUD in healthcare and to expand buprenorphine use; however, even with accessibility near where PWUD access injection equipment, barriers to its use remain. Peer dissemination may be able to facilitate program information sharing and recruitment.KEY MESSAGESPeople who use drugs perceive a mobile health clinic in their neighbourhood as a benefit to their communities and themselves by improving access to healthcare services, providing access to low-threshold buprenorphine dispensation, and offering services without drug use stigma.People who use drugs learned about a mobile health clinic in their neighbourhood largely through word-of-mouth. As a result, people received limited information about the mobile health clinic services creating a barrier to its use.

Role of direct and indirect social and spatial ties in the diffusion of HIV and HCV among people who inject drugs: a cross-sectional community-based network analysis in New Delhi, India.

Background: People who inject drugs (PWID) account for some of the most explosive human immunodeficiency virus (HIV) and hepatitis C virus (HCV) epidemics globally. While individual drivers of infection are well understood, less is known about network factors, with minimal data beyond direct ties. Methods: 2512 PWID in New Delhi, India were recruited in 2017-19 using a sociometric network design. Sampling was initiated with 10 indexes who recruited named injection partners (people who they injected with in the prior month). Each recruit then recruited their named injection partners following the same process with cross-network linkages established by biometric data. Participants responded to a survey, including information on injection venues, and provided a blood sample. Factors associated with HIV/HCV infection were identified using logistic regression. Results: The median age was 26; 99% were male. Baseline HIV prevalence was 37.0% and 46.8% were actively infected with HCV (HCV RNA positive). The odds of prevalent HIV and active HCV infection decreased with each additional degree of separation from an infected alter (HIV AOR: 0.87; HCV AOR: 0.90) and increased among those who injected at a specific venue (HIV AOR: 1.50; HCV AOR: 1.69) independent of individual-level factors (p<0.001). In addition, sociometric factors, for example, network distance to an infected alter, were statistically significant predictors even when considering immediate egocentric ties. Conclusions: These data demonstrate an extremely high burden of HIV and HCV infection and a highly interconnected injection and spatial network structure. Incorporating network and spatial data into the design/implementation of interventions may help interrupt transmission while improving efficiency. Funding: National Institute on Drug Abuse and the Johns Hopkins University Center for AIDS Research.

Understanding the social and spatial relationships that connect people is a key element to stop the spread of infectious diseases. These networks are particularly relevant to combat epidemics among populations that are hard to reach with public health interventions. Network-based approaches, for example, can help to stop HIV or hepatitis C from spreading amongst populations that use injectable drugs. Yet how social and geographic connections such as acquaintances, injection partners, or preferred drug use places impact the risk of infection is still poorly mapped out. To address this question, Clipman et al. focused on people who inject drugs in New Delhi, India, a population heavily impacted by HIV and hepatitis C. Over 2500 people were recruited, each participant inviting their injection partners to also take part. The volunteers answered survey questions, including where they used drugs, and provided a blood sample to be tested. The results showed that, even after adjusting for individual risk factors, where people used drugs and with whom affected their risk of becoming infected with HIV and hepatitis C. In terms of social ties, the likelihood of HIV and hepatitis C infection decreased by about 13% for each person separating a given individual from an infected person. However, geographical networks also had a major impact. Injecting at a popular location respectively increased the odds of HIV and hepatitis C infection by 50% and 69%. In fact, even if the participant was not using drugs at these specific places, having an injection partner who did was enough to increase the risk for disease: for each person separating an individual from the location, the likelihood of being infected with HIV and hepatitis C decreased by respectively 14% and 10%. The results by Clipman et al. highlight how the relationships between physical spaces and social networks contribute to the spread of dangerous diseases amongst people who inject drugs. Ultimately, this knowledge may help to shape better public health interventions that would take into account the importance of geographical locations.

Cross-Sectional and Longitudinal Performance of Creatinine- and Cystatin C-Based Estimating Equations Relative to Exogenously Measured Glomerular Filtration Rate in HIV-Positive and HIV-Negative Persons.

BACKGROUND: Reliable estimates of glomerular filtration rate (GFR) are important in the clinical management of HIV-positive patients. Data on the performance of widely used estimating equations (eGFR) relative to exogenously measured GFR are sparse in this population. METHODS: We evaluated cross-sectional and longitudinal accuracy and bias of eGFR, based on creatinine and cystatin C, relative to disappearance of infused iohexol from plasma (iGFR) in a cohort of participants followed annually for up to 7 years. RESULTS: A total of 222 HIV-positive and 139 HIV-negative participants contributed 1240 visits with valid iGFR and eGFR measures. Estimated GFR based on both creatinine and cystatin C performed the best. Estimated GFR based on creatinine alone overestimated iGFR by 9 mL·min·1.73 m on average and was significantly less accurate in HIV-positive than HIV-negative individuals. The performance of equations based on either creatinine alone or cystatin C alone were significantly affected by participant factors (eg, non-suppressed HIV RNA, nadir CD4 count, hepatitis C virus coinfection). The average iGFR slope was -4% per year in HIV-positive participants. In both HIV-positive and HIV-negative participants, eGFR slope measures were generally unbiased but inaccurate, with only 60%-74% of observations falling within ±5% points of iGFR slope. CONCLUSIONS: Both creatinine and cystatin C have limitations as GFR indices in HIV-positive individuals. Estimated GFR based on both creatinine and cystatin C performed best in our study and may be preferred in HIV-positive persons with kidney disease or comorbidities that place them at high risk for kidney disease.

Longitudinal Assessment of Proximal Tubular Dysfunction in HIV Seropositive and Seronegative Persons: Correlates and Implications.

BACKGROUND: Proximal tubular dysfunction (PTD) is common in HIV-positive persons and has been associated with tenofovir disoproxil fumarate (TDF). However, few studies have assessed the natural history PTD in HIV-positive and -negative individuals, or the association of PTD with the subsequent trajectory of directly measured glomerular filtration rate (mGFR). METHODS: We followed 192 HIV-positive and 100 HIV-negative, nondiabetic participants for 3 years. We measured 3 PTD markers (normoglycemic glycosuria, fractional excretion of phosphorus, and tubular proteinuria) and mGFR (by iohexol disappearance from serum) annually. We used univariate and multivariate generalized estimating equation logistic regression to identify factors associated with PTD across all visits and linear mixed effects models to assess the association between baseline PTD and mGFR slope. RESULTS: Compared with HIV-negative participants, HIV-positive persons that were not taking antiretroviral therapy were at increased risk of PTD (adjusted odds ratio 3.33; 95% confidence interval: 1.65 to 6.71), whereas those taking a TDF-based or a TDF-sparing regimen were not at significantly increased risk of PTD. Among HIV-positive participants, uncontrolled viremia was a strong correlate of PTD. Forty-nine of 55 (89%) participants with PTD at baseline had at least 1 subsequent visit without PTD. There was no association between baseline PTD and rate of decline in mGFR over time. CONCLUSIONS: Poorly controlled HIV may be a stronger risk factor for PTD than TDF use. The individual-level variability of the PTD markers over time was high, potentially limiting their usefulness for routine screening in unselected patients. Baseline PTD was not associated with subsequent mGFR slope.

HIV, Cocaine Use, and Hepatitis C Virus: A Triad of Nontraditional Risk Factors for Subclinical Cardiovascular Disease.

OBJECTIVE: We assessed cross-sectional and longitudinal associations of 3 nontraditional cardiovascular disease risk factors-HIV, cocaine use, and chronic hepatitis C virus infection-with 3 validated markers of subclinical cardiovascular disease: carotid artery plaque, albuminuria, and aortic pulse wave velocity in a well-characterized cohort. APPROACH AND RESULTS: We measured carotid plaque at baseline and after 24 months, urine albumin/creatinine ratio every 6 months, and pulse wave velocity annually for up to 36 months in a predominantly black cohort of 292 participants (100 HIV negative and 192 HIV positive). Thirty-nine percent had chronic hepatitis C virus infection and 20%, 28%, and 52% were never, past, and current cocaine users, respectively. Sixteen percent, 47%, and 64% of those with none, 1 or 2, or all 3 nontraditional risk factors had ≥2 abnormal cardiovascular disease risk markers (P=0.001). In fully adjusted models that included all 3 nontraditional risk factors, HIV infection was independently associated with carotid plaque progression (increase in the number of anatomic segments with plaque), albuminuria (albumin-creatinine ratio >30 mg/g), albuminuria progression (doubling of albumin-creatinine ratio from baseline to a value >30 mg/g), and pulse wave velocity. Cocaine use was associated with an ≈3-fold higher odds of carotid plaque at baseline, and hepatitis C virus infection was significantly associated with a higher risk of carotid plaque progression. CONCLUSIONS: These results suggest that HIV infection, cocaine use, and hepatitis C virus infection are important nontraditional risk factors for cardiovascular disease and highlight the need to understand the distinct and overlapping mechanisms of the associations.

Correlates and Longitudinal Renal and Cardiovascular Implications of FGF23 Levels in HIV-Positive Individuals.

Fibroblast growth factor23 (FGF23), an early marker of kidney dysfunction, is associated with cardiovascular death. Its role in HIV-positive individuals is unknown. We measured FGF23 in 100 HIV-negative and 191 HIV-positive nondiabetic adults with normal baseline estimated glomerular filtration rate (GFR). We measured GFR by iohexol annually, albumin-creatinine ratio (ACR) every 6 months, as well as pulse wave velocity, carotid plaque, and carotid intima media thickness (IMT) at baseline and 2 years. Progressive albuminuria was defined as follow-up ACR ≥2-fold than baseline and ≥30 mg/g. Regression models assessed associations of FGF23 with baseline factors and longitudinal changes in disease markers. FGF23 levels were similar in HIV serostatus. Among HIV-positive persons, factors independently associated with higher baseline FGF23 levels included female (adjusted ratio of geometric means [95% CI],1.46 [1.21,1.76]), serum phosphorus (1.20 [1.03,1.40]), HCV (1.31 [1.10,1.56]) and non-suppressed HIV RNA (1.27 [1.01,1.76]). At baseline, FGF23 was not associated with GFR, albuminuria, carotid plaque, or carotid IMT in cross-sectionally adjusted analysis of HIV-positive individuals. However, higher baseline FGF23 was associated with progressive albuminuria (odds ratio1.48 [95% CI]:1.05,2.08) and a more rapid increase in IMT (13 µm/year, 95% CI,3,24). These findings suggest a role for FGF23 in HIV-positive populations in identifying patients at greater risk for cardiovascular and kidney disease.

Factors associated with iohexol-based glomerular filtration rate slope over 36 months in HIV-negative and HIV-positive individuals.

BACKGROUND: Monitoring kidney function is important in HIV-positive persons, but creatinine-based estimates of glomerular filtration rate (GFR) have limitations. There are little to no data available assessing GFR trends in HIV-positive persons using a gold-standard measure of GFR. METHODS: We measured GFR based on iohexol plasma disappearance (iGFR) annually for 3 years in nondiabetic, HIV-negative and HIV-positive volunteers with normal estimated kidney function. We used mixed linear models to evaluate factors associated with baseline iGFR and iGFR slope. RESULTS: One hundred HIV-negative and 191 HIV-positive, predominantly black individuals (median age 49 years) participated in the study and completed a total of 960 iGFR assessments over a median of 36 months. Despite similar estimated GFR at baseline, average iGFR values were lower in HIV-positive compared with HIV-negative participants (103.2 vs. 110.8, ml/min/1.73 m, P = 0.004). However, subsequent iGFR slope was not significantly different in HIV-positive and HIV-negative participants. In the HIV-positive group, the presence of carotid plaque and hepatitis C virus coinfection were associated with significantly lower iGFR values at baseline. A nonsuppressed HIV RNA level at baseline was associated with a significantly more rapid iGFR decline compared with individuals with HIV RNA less than 400 copies/ml (-4.69 vs. -1.31 ml/min per 1.73 m per year, P = 0.005). Other factors significantly associated with iGFR slope included albuminuria and glycosylated hemoglobin. CONCLUSION: Compared with HIV-negative persons, HIV-positive participants had significantly lower baseline iGFR, despite similar estimated GFR in the two groups. Nonsuppressed HIV RNA at baseline was associated with a more rapid iGFR decline over 3 years.