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Background: Over the last decade, India has had an alarming rise in injection of opioids across several cities. Although scale-up of public sector services for people who inject drugs (PWID) in India has occurred over decades, accessibility has been diminished by fragmented services across physical locations. To circumvent this barrier, and in alignment with the World Health Organization's guidelines to provide comprehensive care to key populations, Integrated Care Centers (ICCs) were established across 8 Indian cities as a public-private service delivery model for providing free single-venue services to PWID. ICCs have been very successful in expanding service availability and convenience for PWID generally. However, few studies from low- and middle-income countries (LMIC) have evaluated how well young PWID (defined as those ≤ 29 years of age) engage with single-venue service models like ICCs or specific services provided in such models. Young PWID are an important subpopulation in India, as they bear a disproportionate burden of new HIV infections because of greater risk and evidence of lower receipt of HIV testing and harm reduction services compared to older PWID. In this comment, we offer insights specific to young PWID drawn from multiple quantitative and qualitative studies examining the reach and effectiveness of ICCs, which may provide generalizable insights into limitations of services for young PWID more broadly in India and globally., Findings: Our studies suggest that while ICCs have expanded service availability, particularly in cities with emerging injection drug use epidemics, population-level reach to foster initial engagement among young PWID can be optimized. Additionally, young PWID who do engage with ICCs experience gaps in substance use treatment receipt and retention, and experience barriers to receipt of ICC services that are distinct from those experienced by older PWID. Notably, HIV incidence among ICC clients is concentrated in young PWID. Finally, ICCs were not intended to reach adolescent PWID, and new services are needed for this subpopulation., Conclusions: In addition to co-locating services, iterative optimization of models such as ICCs should incorporate youth-specific differentiated interventions and be accompanied by policy changes that are critical to improving the reach and effectiveness of harm reduction and HIV services among young PWID in India., (© 2024. The Author(s).)

Introduction: Globally, there have been significant declines in HIV incidence over the past two decades, but this decline is slowing, and in some settings, declines have stalled or are growing-particularly where epidemics are concentrated in key populations (KPs). Understanding temporal changes in HIV incidence among KP is critical yet, due to logistical constraints, there are few sources of longitudinal incidence data, particularly among KP., Methods: We present HIV incidence rates from June 2014 to December 2022 among cisgender men who have sex with men (MSM) and people who inject drugs (PWID) attending community-based integrated care centres (ICCs) in 15 Indian cities. ICCs, established between 2014 and 2017, provide HIV testing and other services to MSM (eight sites) or PWID (eight sites). Client HIV testing data were included in the analysis if they had ≥2 tests and were not positive on the first test. We calculated incidence rates per 100 person-years (PY), stratified by KP, city/site and year. Poisson regression explored associations of incidence with time, age, gender (PWID only) and ICC use., Results: From June 2014 to December 2022, 13,501 clients (5722 MSM, 7779 PWID) had ≥2 HIV tests over a median of 1.8 years. There were a total of 1093 incident HIV acquisitions. Overall incidence rates for MSM and PWID were 1.9/100 PY (95% CI: 1.7-2.2) and 4.1 (3.9-4.4), respectively. Among MSM sites, incidence ranged from 0.4 to 3.5 and in PWID sites from 0.6 to 17.9. From adjusted models, incidence increased by 17% annually among MSM. Among PWID, incidence increased by 11% annually up until 2020 and then decreased by 29% after 2020; when excluding the outlier of New Delhi, incidence was stable among PWID. MSM and PWID 21-25 years old had the highest risk of HIV and among PWID, those more consistently engaged in medication for opioid use disorder were at the lowest risk., Conclusions: While there was substantial geographic variability, MSM and PWID engaged in a free community-based clinic experienced persistently high HIV incidence (>2/100 PY). KP in low- and middle-income countries should be a focus when considering novel strategies such as long-acting pre-exposure prophylaxis to curtail incidence., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Introduction: To achieve epidemic control of infectious diseases, engaging higher-burden populations with accessible diagnostic services is critical. HIV self-testing (HIVST) is a promising option., Methods: We implemented an online HIVST programme for key populations across India. Eligible clients were 18 years or older, self-reported a negative or unknown HIV status and reported not taking antiretroviral therapy. Clients who reported a prior HIV diagnosis were not eligible to receive an HIVST kit. HIVST clients received kits via courier or in person at pre-determined pick-up points supported by trained counselling staff. Virtual counsellors engaged clients online and by phone and offered support to register, access, and complete HIVST free of cost. Virtual counsellors supported clients to report results and engage with follow-up services. Follow-up included linking clients with a positive result to confirmatory testing and HIV care services. We assessed programmatic data across HIV continuum outcomes and conducted a qualitative evaluation through interviews with purposively sampled clients., Results: Between 30 June 2021 and 30 September 2022, 5324 clients ordered an HIVST kit (76% men, 13% women, 7% transgender people, 4% unknown gender). Of the 4282 clients reporting results (94% of those who received a kit), 6% screened positive, among whom 72% (n = 184) completed confirmatory testing. Themes from 41 client interviews included satisfaction about the convenience and privacy of services and the discreet nature of kit delivery. Respondents were drawn to the convenience of HIVST and appreciated gaining courage and comfort throughout the process from virtual counsellor support. For respondents who screened positive, challenges to care linkage included fearing judgemental questions from public providers and wanting more time before starting treatment. Clients shared concerns about kit accuracy and suggested that instructional materials be provided with more diverse language options., Conclusions: Web-based HIVST services with tailored support appeared to facilitate HIV service access and engagement of harder-to-reach populations across India. Assistance from a community-oriented counsellor proved important to overcome literacy barriers and mistrust  in order to support the HIVST process and service linkage. Learnings can inform global efforts to improve the critical step of diagnosis in achieving epidemic control for HIV and other infectious diseases., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

People living with HIV (PWH) have been shown to bear a higher burden of hepatitis B virus (HBV) due to shared routes and risk factors for transmission. Populations such as men who have sex with men (MSM) are at an increased risk of both being infected with HBV and HIV, that places them at higher risk of hepatocellular carcinoma. Using weighted and adjusted multilevel logistic regression, we characterized the prevalence and correlates of hepatitis B surface antigen (HBsAg) among MSM living with HIV across 12 Indian cities from 2012 to 2013. Overall, the prevalence of HBsAg was 8% (range across cities: 0.5%-19%). Being between the ages of 25-34, and 35-44 increased the odds of having chronic HBV infection compared to MSM 24 years or younger. Daily or seasonal employment and being unemployed increased the odds of HBsAg prevalence compared to those with monthly or weekly wages. Sexual risk behaviours such as having had sex with both men and women in the prior 6 months and history of sex work increased the odds of having HBV. Ever having insertive sex with a man or hijra (assigned male at birth, currently identifies as female/nonbinary) was negatively associated with HBV. Despite the existence of efficacious vaccines, HBV continues to have high prevalence among PWHs. Programmes to increase early screening, vaccinations and HBV literacy are urgently needed. Integrating HBV and HIV programmes for MSM populations could be critical in addressing this dual burden and improving outcomes for both infections., (© 2024 John Wiley & Sons Ltd.)

Background: Progress on HIV treatment outcomes for people who inject drugs and men who have sex with men in India has been slow compared with that in other populations. We assessed whether HIV treatment incentives would improve outcomes among these groups., Methods: We did a matched-pair, cluster randomised trial in 16 sites (eight for people who inject drugs and eight for men who have sex with men) across 15 cities in India. We recruited cohorts of HIV-positive people who inject drugs or men who have sex with men who were antiretroviral therapy (ART)-naive or had less than 12 months of ART exposure. We randomised sites to provide incentives or usual care. At intervention sites, we provided incentive vouchers, which could be exchanged for food or household goods, for attending motivational interviewing sessions and timely appointments at government ART clinics. An ART-naive participant meeting all targets could earn the equivalent to 14 days' wages over 12 months. The primary outcome was survival with viral suppression at 12 months. We used an intention-to-treat analytic approach appropriate for matched-pair cluster randomised trials, adjusting for baseline viral suppression. This study was registered with ClinicalTrials.gov, NCT02969915, and is complete., Findings: Between Oct 30, 2017, and Oct 12, 2018, we recruited 1200 people who inject drugs and 1114 men who have sex with men living with HIV. Among people who inject drugs, 154 (12·8%) identified as female gender and 1046 (87·2%) as male. The site median percentage of participants earning one or more incentives was 96·1% (IQR 93·7-98·1). At 12 months, HIV viral suppression was 31·9% (n=383) among people who inject drugs and 52·1% (n=580) among men who have sex with men. The incentive intervention was not associated with significantly improved survival with viral suppression compared with usual care (adjusted prevalence difference 9·6 percentage points, 95% CI -4·4 to 23·7)., Interpretation: Despite high intervention engagement, incentives did not improve survival with viral suppression among people who inject drugs and men who have sex with men living with HIV in India. The poor outcomes overall underscore the need for innovative, multilevel approaches to engage marginalised people living with HIV in low-income and middle-income settings., Funding: US National Institutes of Health, Elton John AIDS Foundation., Competing Interests: Declaration of interests SSS has received grants, products and honoraria from Gilead Sciences and Abbott Laboratories. SSS also serves on the Board of Trustees of YR Gaitonde Medical Educational and Research Foundation. SHM receives materials support from Abbott Diagnostics. Other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (© 2024 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Access to direct acting antivirals (DAAs) may be associated with reductions in hepatitis C virus (HCV) viremia prevalence among people with human immunodeficiency virus (PWH). Among 3755 PWH, estimated HCV viremia prevalence decreased by 94.0% from 36% (95% confidence interval [CI], 27%-46%) in 2009 (pre-DAA era) to 2% (95% CI, 0%-4%) in 2021 (DAA era). Male sex, black race, and older age were associated with HCV viremia in 2009 but not in 2021. Injection drug use remained associated with HCV viremia in 2009 and 2021. Targeted interventions are needed to meet the HCV care needs of PWH who use drugs., Competing Interests: Potential conflicts of interest. M. S. reports research funds paid to his institution by Janssen, Vir, and GSK (HBV); and consulting fees from AbbVie, Antios, Assembly Bio, Atea, GSK, Gilead, Precision Bio, and Vir. O. F. N. reports research funds paid to her institution by Abbvie, Inc; and consulting fees from Gilead. D. T. reports consulting fees from Merck, Excision Bio, and Evrys Bio. S. H. M. reports materials support from Abbott Diagnostics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 75 th%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., (© 2023 Society for the Study of Addiction.)

The relationships between place (e.g., neighborhood) and HIV are commonly investigated. As measurements of place are multivariate, most studies apply some dimension reduction, resulting in one variable (or a small number of variables), which is then used to characterize place. Typical dimension reduction methods seek to capture the most variance of the raw items, resulting in a type of summary variable we call "disadvantage score". We propose to add a different type of summary variable, the "vulnerability score," to the toolbox of the researchers doing place and HIV research. The vulnerability score measures how place, as known through the raw measurements, is predictive of an outcome. It captures variation in place characteristics that matters most for the particular outcome. We demonstrate the estimation and utility of place-based vulnerability scores for HIV viral non-suppression, using data with complicated clustering from a cohort of people with histories of injecting drugs., (© 2024. The Author(s).)

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., Competing Interests: Conflict of Interest DT: medical editing for UpToDate; scientific advisor to Excision Bio, Evrys Bio, and Merck. OFN research grants from Abbvie paid to institution; scientific consulting for Gilead. SM: materials support from Abbott. Other authors: no conflict declared.

Lifetime exposures to violence among men who have sex with men (MSM) are associated with multiple psychosocial health risks and can affect engagement and outcomes of HIV treatment. This study a) explored relationships between levels of exposures to violence and HIV care continuum outcomes among MSM living with HIV in India, and b) identified psychosocial correlates of HIV care continuum outcomes among MSM living with HIV and those with lifetime cumulative exposures to violence (CVE). CVE referred to exposures to violence in both childhood and adulthood. This cross-sectional analysis used survey data collected between August 2016 and May 2017 from 1763 men who have sex with men living with HIV across 10 cities in India, using respondent-driven sampling. We found that higher levels of violence exposure were significantly associated with lower awareness of HIV positive status, and lower likelihood of initiating antiretroviral therapy. Compared with MSM living with HIV that had no CVE, those with CVE were more likely to report perpetration of interpersonal violence, alcohol misuse, depressive symptoms, and HIV transmission risk behaviors and to have two to four co-occurring psychosocial problems. In multivariable analysis with the subset of MSM with CVE, psychosocial correlates significantly associated with at least one HIV care continuum outcome were HIV transmission risk behaviors, perpetration of interpersonal violence, depression, and alcohol misuse. The findings highlight the need for integrating care for lifetime violence exposures and associated behavioral problems in HIV care settings for men who have sex with men living with HIV in India., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sabri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Monitoring key populations' progress towards UNAIDS 90-90-90 targets is essential to achieving HIV/AIDS epidemic control. Using serial cross-sectional data, we evaluated changes in HIV care continuum among people who inject drugs(PWID) and men who have sex with men(MSM) in India. Cross-sectional baseline (2012/2013) and follow-up (2016/2017) samples were recruited using respondent-driven sampling across 21 cities. All participants were tested for HIV and RNA measured in HIV-positive participants. Linear regression was used to model temporal site-level changes in continuum indicators in MSM versus PWID. At baseline, we recruited 2,544 HIV-infected PWID and 1,086 HIV-infected MSM. At follow-up, we recruited 2,517 HIV-infected PWID and 1,763 HIV-infected MSM. At baseline, there were no significant differences in continuum indicators between MSM and PWID. At follow-up, compared to PWID, the proportion of MSM reaching each care continuum indicator-awareness of status, receipt of care, ART use, viral suppression-increased by 15-33 percentage points: 78% of MSM versus 49% of PWID were aware of their status ( p  < 0.01); 56% of MSM versus 32% of PWID were virologically suppressed ( p  = 0.05). MSM showed marked improvements across the care continuum, whereas PWID lagged and may require additional intervention. Differential improvement in HIV engagement may necessitate population-specific interventions and routine surveillance to facilitate HIV elimination.

Background: The social processes around initiating injection may be well-suited to intervention, yet there is substantial heterogeneity in the reported experiences of people who inject drugs (PWID) who assist with another individual's first drug injection. We aimed to describe the lifetime prevalence and context of providing initiation assistance among a cohort of PWID., Methods: Participants of the AIDS Linked to the IntraVenous Experience (ALIVE) cohort of PWID in Baltimore, Maryland (n=848) were surveyed during 2019-2020 about assisting with another person's first injection. Associations between factors related to injection risk and history of providing assistance were estimated using logistic regression models adjusted for sociodemographic and behavioral characteristics., Results: At baseline, participants were primarily male (66.1%), black (82.9%), aged a median of 42 years, and had been injecting a median of 18 years. Overall, 19% (n=157) of participants reported ever providing assistance for a median of 2 people (Interquartile Range: 1-4). Having hepatitis C infection (adjusted Odds Ratio [95% Confidence Interval]: 2.5 [1.4-4.6]), syringe sharing (2.2 [1.2-3.9]), and injecting ≥3 times per day (2.0 [1.2-3.4]) at study enrollment were associated with a history of assistance. Participants primarily assisted friends (58.0%), acquaintances (29.9%), and partners (21.7%). Common reasons for assisting were the other person's lack of injection knowledge (73.7%) or sharing drugs (44.9%). Additional reasons included to prevent injury., Conclusion: PWID with a history of assisting with another person's first injection exhibited heightened vulnerability to infections and more frequent substance use. Expanding implementation of interventions with an emphasis on harm reduction is needed., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Respondent-driven sampling (RDS), a network recruitment approach, is effective at reaching people who inject drugs (PWID), but other strategies may be needed to reach PWID at risk or living with HIV and/or Hepatitis C (HCV). We examined the impact of integrating geospatially targeted community-based HIV/HCV testing with an RDS survey., Methods: PWID were recruited between 2019 and 2021 in Patti and Gorakhpur, India, in a two-phased approach for identifying PWID living with HIV/HCV. Phase 1 was an RDS survey, in which participants reported injection venues. Venues with the highest prevalence of HIV/HCV viremia were selected for Phase 2: community-based testing. All participants underwent rapid HIV and HCV testing and viral load quantification. Using Pearson's chi-squared test, two-sided exact significance tests, and t-tests, we compared prevalence and identification rates for each of the primary outcomes: the number of PWID 1) living with HIV/HCV, 2) undiagnosed, and 3) viremic., Results: Both approaches identified large numbers of PWID (n∼500 each; N=2011) who were living with HIV/HCV and had transmission potential (i.e., detectable viremia). The community-based approach identified a higher proportion of individuals living with HCV (76.4% vs. 69.6% in Gorakhpur and 36.3% vs. 29.0% in Patti). Community-based testing was also faster at identifying PWID with detectable HIV viremia. Both approaches identified PWID with varying demographic characteristics., Conclusions: Community-based testing was more efficient than RDS overall, but both may be required to reach PWID of varying characteristics. Surveillance should collect data on injection venues to facilitate community-based testing and maximize case identification., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: India is facing overlapping opioid injection and HIV epidemics among people who inject drugs (PWID) in several cities. Integrated Care Centers (ICCs) provide single-venue HIV and substance use services to PWID. We evaluated PWID engagement in daily observed buprenorphine treatment at 7 ICCs to inform interventions., Methods: We analyzed 1-year follow-up data for PWID initiating buprenorphine between 1 January - 31 December 2018, evaluating receipt frequency, treatment interruptions (no buprenorphine receipt for 60 consecutive days with subsequent re-engagement), and drop-out (no buprenorphine receipt for 60 consecutive days without re-engagement). Using descriptive statistics, we explored differences between ICCs in the opioid-endemic Northeast region and ICCs in the emerging opioid epidemic North/Central region. We used a multivariable logistic regression model to determine predictors of treatment drop-out by 6 months., Results: 1312 PWID initiated buprenorphine (76% North/Central ICCs vs. 24% Northeast ICCs). 31% of PWID in North/Central, and 25% in Northeast ICCs experienced ≥ 1 treatment interruption in 1 year. Over 6 months, 48% of PWID in North/Central vs. 60% in Northeast ICCs received buprenorphine ≤ 2 times/week (p < 0.0001). A third of PWID in North/Central vs. half in Northeast ICCs experienced treatment drop-out by 6 months (p < 0.001). In the multivariable model, living in Northeast cities was associated with increased odds of drop-out while counseling receipt was associated with decreased odds., Conclusions: Retention among PWID initiating buprenorphine at ICCs was comparable to global reports. However, regional heterogeneity in retention, and low daily buprenorphine receipt suggest patient-centered interventions adapted to regional contexts are urgently needed., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Restrictions to curb the first wave of COVID-19 in India resulted in a decline in facility-based HIV testing rates, likely contributing to increased HIV transmission and disease progression. The programmatic and economic impact of COVID-19 on index testing, a standardized contact tracing strategy, remains unknown., Methods: Retrospective programmatic and costing data were analyzed under a US government-supported program to assess the pandemic's impact on the programmatic outcomes and cost of index testing implemented in two Indian states (Maharashtra and Andhra Pradesh). We compared index testing continuum outcomes during lockdown (April-June 2020) and post-lockdown (July-Sept 2020) relative to pre-lockdown (January-March 2020) by estimating adjusted rate ratios (aRRs) using negative binomial regression. Startup and recurrent programmatic costs were estimated across geographies using a micro-costing approach. Per unit costs were calculated for each index testing continuum outcome., Results: Pre-lockdown, 2431 index clients were offered services, 3858 contacts were elicited, 3191 contacts completed HIV testing, 858 contacts tested positive, and 695 contacts initiated ART. Compared to pre-lockdown, the number of contacts elicited decreased during lockdown (aRR = 0.13; 95% CI: 0.11-0.16) and post-lockdown (aRR = 0.49; 95% CI: 0.43-0.56); and the total contacts newly diagnosed with HIV also decreased during lockdown (aRR = 0.22; 95% CI: 0.18-0.26) and post-lockdown (aRR = 0.52; 95% CI: 0.45-0.59). HIV positivity increased from 27% pre-lockdown to 40% during lockdown and decreased to 26% post-lockdown. Further, ART initiation improved from 81% pre-lockdown to 88% during lockdown and post-lockdown. The overall cost to operate index testing was $193,457 pre-lockdown and decreased during lockdown to $132,177 (32%) and $126,155 (35%) post-lockdown. Post-lockdown unit cost of case identification rose in facility sites ($372) compared to pre-lockdown ($205), however it decreased in community-based sites from pre-lockdown ($277) to post-lockdown ($166)., Conclusions: There was a dramatic decline in the number of index testing clients in the wake of COVID-19 restrictions that resulted in higher unit costs to deliver services; yet, improved linkage to ART suggests that decongesting centres could improve efficiency. Training index testing staff to provide support across services including non-facility-based HIV testing mechanisms (i.e., telemedicine, HIV self-testing, community-based approaches) may help optimize resources during public health emergencies., (© 2022. The Author(s).)

People living with (PLWH) and at risk for HIV and people who use drugs (PWUD) are at heightened risk for health consequences of COVID-19 because of compromised immunity and high comorbidities. We studied their use of COVID-19 testing during the first year of the COVID-19 pandemic. Eight NIDA funded cohorts across North America in the Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) administered multiple waves of a COVID-19 survey. Respondents were at least 18 years of age, half PLWH, and many active substance users. Wave one of the COVID-19 survey was May-November, 2020 and wave two October 2020-April 2021. Associations of COVID-19 testing with demographics, socio-demographics, substance use, and HIV-status were assessed. Of the 3762 responses from 2331 individuals, half reported ever COVID-19 testing (49.1 %), with 4.3 % reporting a positive test (163/3762 surveys=4.3 %) and 41.5 % of people reporting current symptoms reported having been tested. In multivariable analysis adjusting for age, sex, and cohort type associations with COVID-19 testing included African American/Black identification compared to Caucasian/white (adjusted odds ratio (AOR)= 0.68; 95 % confidence interval (CI) 0.53, 0.88); being unemployed (AOR=0.61; 95 % CI 0.51, 0.73), and living with HIV (AOR=0.76; 95 % CI0.65, 0.90). Findings from these C3PNO COVID-19 modules suggests that in the first year of the pandemic COVID-19 testing was not broadly accessed by these marginalized populations including PLWH and those unemployed. Factors associated with not testing may also parallel those for vaccination and identify populations needing better access to COVID-19 prevention., Competing Interests: Conflict of Interest No conflict declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The COVID-19 pandemic disrupted the normal delivery of HIV care, altered social support networks, and caused economic insecurity. People with HIV (PWH) are vulnerable to such disruptions, particularly if they have a history of substance use. We describe engagement in care and adherence to antiretroviral therapy (ART) for PWH during the pandemic., Methods: From May 2020 to February 2021, 773 PWH enrolled in 6 existing cohorts completed 1495 surveys about substance use and engagement in HIV care during the COVID-19 pandemic. We described the prevalence and correlates of having missed a visit with an HIV provider in the past month and having missed a dose of ART in the past week., Results: Thirteen percent of people missed an HIV visit in the past month. Missing a visit was associated with unstable housing, food insecurity, anxiety, low resiliency, disruptions to mental health care, and substance use including cigarette smoking, hazardous alcohol use, cocaine, and cannabis use. Nineteen percent of people reported missing at least one dose of ART in the week prior to their survey. Missing a dose of ART was associated with being a man, low resiliency, disruptions to mental health care, cigarette smoking, hazardous alcohol use, cocaine, and cannabis use, and experiencing disruptions to substance use treatment., Conclusions: Social determinants of health, substance use, and disruptions to mental health and substance use treatment were associated with poorer engagement in HIV care. Close attention to continuity of care during times of social disruption is especially critical for PWH., Competing Interests: Declaration of Competing Interests No conflict declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Men who have sex with men (MSM) in low-to-middle-income countries bear a high burden of HIV and a significant proportion marry women to satisfy socio-cultural norms. It has previously been demonstrated that HIV prevalence is higher among married versus unmarried MSM, but limited data are available on HIV prevalence among their wives., Methods: We recruited 149 married MSM couples where the husband disclosed his MSM behavior to his wife (disclosed MSM) and 150 married MSM who had not disclosed their MSM behavior to their wives (undisclosed MSM), in three Indian cities. All participants completed interviewer-administered surveys and underwent HIV testing. Multivariable logistic regression was used to assess correlates of HIV among wives of MSM. Descriptive statistics were used to compare characteristics of disclosed and undisclosed MSM., Results: HIV prevalence in disclosed MSM, their wives, and undisclosed MSM was 46.9%, 27.9%, and 34.9%, respectively. In multivariable analysis, the strongest predictor of HIV prevalence among wives of MSM was husband's HIV positive status (adjusted odds ratio: 13.4; 95% confidence interval: 5.44-33.2). Both disclosed and undisclosed MSM reported high levels of risk behavior including infrequent condom use. Most undisclosed MSM reported that they did not intend to disclose MSM behavior due to stigma., Conclusions: We observed an extremely high HIV prevalence among women married to MSM despite low levels of individual risk behavior. Interventions are urgently needed in this vulnerable population particularly given the challenges related to disclosure of same sex behavior among their husbands.

Objective: To examine the association of drug use stigma with antiretroviral therapy (ART) use and HIV viral suppression among people with HIV who inject drugs in India., Design: Cross-sectional biobehavioral survey., Methods: Between August 2016 and May 2017, persons aged at least 18 years who reported injection drug use in the past 2 years were recruited via respondent-driven sampling (RDS) in 12 Indian cities (approximately 1000 per city). The analysis was restricted to participants with laboratory-confirmed HIV infection who self-reported a prior HIV diagnosis and were eligible for ART per concurrent national HIV treatment guidelines. Enacted and internalized drug use stigma were each measured by five to six-item subscales. The study outcomes were HIV viral suppression (<150 copies/ml) and self-reported past 30-day ART use. RDS-II weighted multivariable logistic regression with a city-level random-intercept was used to estimate adjusted odds ratios (aOR) and corresponding 95% confidence intervals (CIs)., Results: Among 971 ART-eligible participants previously diagnosed with HIV, 65.1% reported ART use and 56.1% were virally suppressed. Reporting any enacted stigma (vs. none) was associated with lower odds of ART use [aOR = 0.26 (95% CI = 0.15-0.44)] and viral suppression [aOR = 0.49 (95% CI = 0.31-0.78)]. High internalized stigma scores (>median vs. ≤median) were associated with lower odds of viral suppression among participants aged at least 35 years [aOR = 0.51 (95% CI = 0.27-0.97)] but not among participants aged less than 35 years [aOR = 1.22 (95% CI = 0.57-2.60)]. Similar associations were observed in analyses restricted to participants ever linked to HIV care., Conclusion: Drug use stigma may be a barrier to HIV viral suppression among people with HIV who inject drugs, thereby hindering efforts to achieve HIV control., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The COVID-19 pandemic has threatened to diminish gains in HIV epidemic control and impacts are likely most profound among key populations in resource-limited settings. We aimed to understand the pandemic's impact on HIV-related service utilization among men who have sex with men (MSM) and people who inject drugs (PWID) across India., Methods: Beginning in 2013, we established integrated care centres (ICCs) which provide HIV preventive and treatment services to MSM and PWID across 15 Indian sites. We examined utilization patterns for an 18-month period covering 2 months preceding the pandemic (January-February 2020) and over the first and second COVID-19 waves in India (March 2020-June 2021). We assessed: (1) unique clients accessing any ICC service, (2) ICC services provided, (3) unique clients tested for HIV and (4) HIV diagnoses and test positivity. Among an established cohort of PWID/MSM living with HIV (PLHIV), we administered a survey on the pandemic's impact on HIV care and treatment (June-August 2020)., Results: Overall, 13,854 unique clients visited an ICC from January 2020 to June 2021. In January/February 2020, the average monthly number of clients was 3761. Compared to pre-pandemic levels, the number of clients receiving services declined sharply in March 2020, dropping to 25% of pre-pandemic levels in April/May 2020 (first wave), followed by a slow rebound until April/May 2021 (second wave), when there was a 57% decline. HIV testing followed a similar trajectory. HIV test positivity changed over time, declining in the first wave and reaching its nadir around July 2020 at ∼50% of pre-pandemic levels. Positivity then increased steadily, eventually becoming higher than pre-pandemic periods. The second wave was associated with a decline in positivity for MSM but was relatively unchanged for PWID. Among 1650 PLHIV surveyed, 52% of PWID and 45% of MSM reported the pandemic impacted their ability to see an HIV provider. MSM had barriers accessing sexually transmitted infection testing and partner HIV testing., Conclusions: The COVID-19 pandemic led to significant decreases in HIV-related service utilization among key populations in India. This presents an opportunity for increased transmission and patients presenting with advanced disease among groups already disproportionately impacted by HIV., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Men who have sex with men (MSM) bear a disproportionately high burden of new HIV infections while lagging behind other populations with respect to engagement across the HIV care continuum. General risk factors for condomless anal intercourse (CAI) among MSM are well studied but there is a paucity of partner-level data, where emerging evidence suggests that much of the variation in condom use occurs., Methods: MSM were recruited across 10 cities in India using respondent-driven sampling (RDS) from 2016-17. Among the individuals who reported sexual intercourse in the prior 6 months, condom use and partner characteristics of the last 4 partners were captured. Correlates of CAI at the individual and partner level were determined using Poisson regression models using generalized estimating equations and incorporating RDS-II weights, which weights estimates for the participant's network size., Results: Among the 8,086 individuals, 21,723 sexual partnerships were analyzed. The prevalence of CAI was 46.9% and most partners were casual or one-time (70.7%) with partner HIV status reported as unknown in 42.6% of the sexual encounters. In multivariable analyses, partner-level characteristics associated with higher likelihood of CAI included unknown partner HIV status (aPR vs. known HIV negative partner: 1.34; 95% confidence interval (CI): 1.27-1.43) and use of alcohol/ drugs prior to intercourse either sometimes (aPR 1.42; 95% CI: 1.33-1.51) or always (aPR 1.31; 95% CI: 1.23-1.41). At an individual level, any HIV treatment literacy was associated with a lower likelihood of CAI (aPR 0.80; 95% CI: 0.74-0.86)., Conclusions: To reduce HIV transmission among this population of MSM across India, combination interventions are likely needed. Interventions targeting substance use and education as well as initiatives to increase self-testing are urgently needed among MSM in India and have the potential to reduce HIV transmission in this high-risk population. Trial registration ClinicalTrials.gov Identifier: NCT01686750. Date of Registration: September 18, 2012., (© 2022. The Author(s).)

Background: Eliminating hepatitis C virus (HCV) will require effective treatment delivery to persons with substance use disorders (SUDs). We evaluated the relationship between ledipasvir/sofosbuvir treatment persistence (receiving 84 tablets), adherence, and sustained virologic response (SVR) in persons with human immunodeficiency virus (HIV)/HCV coinfection., Methods: Of the 144 participants with HIV/HCV and SUDs, 110 initiated a 12-week treatment course under 1 of 3 conditions (usual care, peer mentors, and cash incentives). We used self-report, pharmacy pill counts, and expected date of refill to examine adherence. Persistent participants were categorized as high adherence (taking ≥90% of doses) or low adherence (taking <90% of doses)., Results: Most participants persisted on treatment after initiation (n = 105), with 95% (n = 100) achieving SVR. One third (34%) of participants had moderate/heavy alcohol use by the biomarker phosphatidylethanol ([Peth] ≥50 ng/mL), and 44% had urine toxicology positive for cocaine or heroin at enrollment. The proportion of persons with high adherence was 72% (n = 76), and the proportion of persons with low adherence was 28%. Although low adherence was associated with moderate/heavy alcohol use by PEth (relative risk = 2.77; 95% confidence interval, 1.50-5.12), SVR did not vary according to adherence (P = .702), and most participants (97%) with low adherence achieved SVR., Conclusions: Treatment persistence led to high SVR rates among persons with HIV/HCV, despite imperfect adherence and SUDs., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (© 2021 Society for the Study of Addiction.)

Objective: The COVID-19 pandemic has dramatically impacted mental health, increasing rates of substance misuse. Resilience is a positive adaptation to stress that may act as a buffer against adverse mental health outcomes. Based on prior knowledge, we hypothesized that PLWH would display higher resilience than HIV-uninfected peers, and that high resilience would be associated with lower risk of substance misuse., Methods: This analysis of the Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) included data from six USA cohorts that administered a COVID-19-related survey with a 3-month follow-up during May 2020 and March 2021. All data was self-reported. The Brief Resilience Scale and General Anxiety Disorder-7 were utilized. Primary analyses consisted of multivariate generalized linear mixed models with random intercepts using binary logistic regression., Results: A total of 1430 participants completed both surveys, of whom 670 (46.9%) were PLWH. PLWH had lower odds of anxiety (OR=0.67, 95% CI: 0.51-0.89) and higher odds of high resilience (OR=1.21, 95% CI: 1.02-1.44) than HIV-uninfected participants, adjusted for covariates. The presence of anxiety was associated with higher risk of misuse of all substances. High resilience was associated with lower risk of anxiety and misuse of substances, adjusted for covariates., Conclusions: Psychological resilience was associated with lower risk of anxiety and substance misuse, potentially serving as a buffer against poor mental and behavioral health during the COVID-19 pandemic. Further research is needed to identify pathways of resilience in the context of substance misuse and comprehensive resilience-focused interventions., (Copyright © 2022. Published by Elsevier B.V.)

Background: Understanding the sources of HIV transmission provides a basis for prioritizing HIV prevention resources in specific geographic regions and populations. This study estimated the number, proportion, and rate of HIV transmissions attributable to individuals along the HIV care continuum within different HIV transmission risk groups in 6 US cities., Methods: We used a dynamic, compartmental HIV transmission model that draws on racial behavior-specific or ethnic behavior-specific and risk behavior-specific linkage to HIV care and use of HIV prevention services from local, state, and national surveillance sources. We estimated the rate and number of HIV transmissions attributable to individuals in the stage of acute undiagnosed HIV, nonacute undiagnosed HIV, HIV diagnosed but antiretroviral therapy (ART) naïve, off ART, and on ART, stratified by HIV transmission group for the 2019 calendar year., Results: Individuals with undiagnosed nonacute HIV infection accounted for the highest proportion of total transmissions in every city, ranging from 36.8% (26.7%-44.9%) in New York City to 64.9% (47.0%-71.6%) in Baltimore. Individuals who had discontinued ART contributed to the second highest percentage of total infections in 4 of 6 cities. Individuals with acute HIV had the highest transmission rate per 100 person-years, ranging from 76.4 (58.9-135.9) in Miami to 160.2 (85.7-302.8) in Baltimore., Conclusion: These findings underline the importance of both early diagnosis and improved ART retention for ending the HIV epidemic in the United States. Differences in the sources of transmission across cities indicate that localized priority setting to effectively address diverse microepidemics at different stages of epidemic control is necessary., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although drug use stigma is globally pervasive, quantitative evidence of its role in hepatitis C virus (HCV) transmission is limited. We evaluated the psychometric properties of a drug use stigma scale and examined the association between drug use stigma and active HCV infection among a community-based sample of people who inject drugs (PWID) in India., Methods: Between 8/2016 and 5/2017, a cross-sectional sample of PWID was recruited from 12 Indian cities (~1000/city) using respondent-driven sampling. Participants were ≥18 years old and reported injection drug use (IDU) in the past 2 years. Multivariable logistic regression with a random-intercept for each city was used to estimate adjusted odds ratios (aOR) of active HCV infection (RNA>30 IU/mL). Analyses incorporated RDS-II weights., Results: Of 11,663 participants, 73.1% reported IDU in the past 6 months and 33.8% had active HCV infection. Exploratory factor analysis yielded a four-factor solution of enacted, vicarious, felt normative and internalized drug use stigma with high internal consistency (Cronbach's α: 0.85-0.92). In analyses adjusted for age, gender, northeast region, education, homelessness, incarceration, alcohol dependence, HIV status, frequency of IDU, and ever sharing needles/syringes, PWID reporting any enacted stigma had greater odds of active HCV infection (aOR = 1.27 [95% CI = 1.13-1.43]) as did PWID with internalized stigma scores in the highest quartile (vs. lowest quartile; aOR = 1.69 [95% CI = 1.11-2.56]). Among PWID who reported IDU in the past 6 months, multiple forms of stigma were associated with higher frequency of IDU, sharing needles/syringes, having multiple injection partners, and IDU in public spaces., Conclusion: Using a multidimensional drug use stigma scale, various forms of stigma were significantly associated with active HCV infection and injection drug use-related risk behaviors. Collectively, these data suggest that drug use stigma may play a role in HCV transmission and impede efforts to achieve HCV elimination. Strategies to diminish drug use stigma are warranted., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aims: Implementing effective interventions for HCV requires a detailed understanding of local transmission dynamics and geospatial spread. Little is known about HCV phylodynamics, particularly among high-burden populations, such as people who inject drugs (PWID)., Approach and Results: We used 483 HCV sequences and detailed individual-level data from PWID across four Indian cities. Bayesian phylogeographic analyses were used to evaluate transmission hotspots and geospatial diffusion of the virus. Phylogenetic cluster analysis was performed to infer epidemiologic links and factors associated with clustering. A total of 492 HIV sequences were used to draw comparisons within the same population and, in the case of coinfections, evaluate molecular evidence for shared transmission pathways. Overall, 139/483 (28.8%) of HCV sequences clustered with a median cluster size of 3 individuals. Genetically linked participants with HCV were significantly younger and more likely to be infected with HCV subtype 3b as well as to live and inject close to one another. Phylogenetic evidence suggests likely ongoing HCV infection/reinfection with limited support for shared HIV/HCV transmission pathways. Phylogeographic analyses trace historic HCV spread back to Northeastern India and show diffusion patterns consistent with drug trafficking routes., Conclusions: This study characterizes HCV phylodynamics among PWID in a low and middle-income country setting. Heterogeneity and recent genetic linkage of HCV across geographically disparate Indian states suggest that targeted interventions could help prevent reimportation of virus through drug trafficking routes., (© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Introduction: There are limited data on the impact of COVID-19-associated disruptions and novel HIV service delivery strategies among key populations (KPs) in low- and middle-income countries. In March 2020, in response to COVID-19, the Government of India revised HIV service delivery policies to include community antiretroviral therapy (ART) distribution and multi-month dispensing (MMD) of ART for all people living with HIV (PLHIV)., Methods: To assess the acceptability of these adaptations and impact of the pandemic among KPs, we conducted focus groups in November-December 2020 with purposively sampled men who have sex with men (MSM), female sex workers (FSWs) and transgender women (TGW) in Telangana and Maharashtra. Seven discussions were conducted. Topics included HIV service access, risk behaviours, economic security and feedback to ensure service continuity. Inductive coding identified themes across topics., Results: Forty-four individuals aged 20-49 years participated in discussions (13 MSM; 16 FSW; and 15 TGW). Twenty-four participants self-identified as living with HIV. People not living with HIV reported challenges in accessing HIV antibody testing at hospitals due to travel restrictions and fear of contracting COVID-19. Participants accessed HIV antibody testing using transportation arranged by community-based organizations after lockdowns eased. PLHIV reported uninterrupted ART refills and generally consistent adherence; however, there were experiences of delayed CD4 and HIV RNA testing. Participants shared appreciation for MMD as it saved time, money, and reduced exposure to COVID-19. Participants expressed gratitude for home deliveries which enabled ART access, yet shared concerns about home-based services causing confidentiality breaches with family/neighbours. Participants voiced preferences for community-based service provision due to proximity, convenient hours, and welcoming environments compared to public hospitals. Other requests included support for income, employment, nutrient-rich food and more accessible mental health, HIV, and other health services., Conclusions: COVID-19 restrictions had a greater impact on access to HIV antibody, CD4, and RNA testing services compared to ART access. High acceptance of MMD and community-based services support the continued role of differentiated service delivery models to improve KP access to HIV antibody, CD4, RNA testing services, convenient ART retrieval, and integrated services beyond HIV, which may be critical for survival and wellbeing., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Objectives: The HIV epidemic in India is concentrated in key populations such as people who inject drugs (PWID). New HIV infections are high among young PWID (≤30 years of age), who are hard to engage in services. We assessed perspectives of young PWID to guide development of youth-specific services., Setting: We conducted focus group discussions (FGDs) with PWID and staff at venues offering services to PWID in three Indian cities representing historical and emerging drug use epidemics., Participants: PWID were eligible to participate if they were between 18 and 35 years, had initiated injection as adolescents or young adults and knew adolescent PWID in their networks. 43 PWID (81% male, 19% female) and 10 staff members participated in FGDs. A semistructured interview guide was used to elicit participants' narratives on injection initiation experiences, barriers to seeking harm reduction services, service delivery gaps and recommendations to promote engagement. Thematic analysis was used to develop an explanatory model for service engagement in each temporal stage across the injection continuum., Results: Injection initiation followed non-injection opioid dependence. Lack of services for non-injection opioid dependence was a key gap in the preinjection initiation phase. Lack of knowledge and reliance on informal sources for injecting equipment were key reasons for non-engagement in the peri-injection phase. Additionally, low-risk perception resulted in low motivation to seek services. Psychosocial and structural factors shaped engagement after established injection. Housing and food insecurity, and stigma disproportionately affected female PWID while lack of confidential adolescent friendly services impeded engagement by adolescent PWID., Conclusions: Development of youth-specific services for young PWID in India will need to address unique vulnerabilities and service gaps along each stage of the injection continuum. Scaling-up of tailored services is needed for young female PWID and adolescents, including interventions that prevent injection initiation and provision of confidential harm reduction services., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Population-level prevalence of detectable HIV viraemia (PDV) has been proposed as a metric for monitoring the population-level effectiveness of HIV treatment as prevention. We aimed to characterise temporal changes in PDV in people who inject drugs (PWID) and men who have sex with men (MSM) in India and evaluate community-level and individual-level associations with cross-sectional HIV incidence., Methods: We did a serial cross-sectional study in which baseline (from Oct 1, 2012, to Dec 19, 2013) and follow-up (from Aug 1, 2016, to May 28, 2017) respondent-driven sampling (RDS) surveys were done in MSM (ten community sites) and PWID (12 community sites) across 21 cities in India. Eligible participants were those aged 18 years or older who provided informed consent and possessed a valid RDS referral coupon. Annualised HIV incidence was estimated with validated multiple-assay algorithms. PDV was calculated as the percentage of people with detectable HIV RNA (>150 copies per mL) in a community site. Community-level associations were determined by linear regression. Multivariable, multilevel Poisson regression was used to assess associations with recent HIV infection., Findings: We recruited 21 990 individuals in the baseline survey and 21 726 individuals in the follow-up survey. The median community-level HIV incidence estimate increased from 0·9% (range 0·0-2·2) at baseline to 1·5% (0·5-3·0) at follow-up in MSM and from 1·6% (0·5-12·4) to 3·6% (0·0-18·4) in PWID. At the community-level, every 1 percentage point increase in baseline PDV and temporal change in PDV between surveys was associated with higher annualised HIV incidence at follow-up: for baseline PDV β=0·41 (95% CI 0·18-0·63) and for change in PDV β=0·52 (0·38-0·66). After accounting for individual-level risk factors, every 10 percentage point increase in baseline PDV and temporal change in PDV was associated with higher individual-level risk of recent HIV infection at follow-up: adjusted risk ratio 1·85 (95% CI 1·44-2·37) for baseline PDV and 1·81 (1·43-2·29) for change in PDV., Interpretation: PDV was temporally associated with community-level and individual-level HIV incidence. These data support scale-up of treatment as prevention programmes to reduce HIV incidence and the programmatic use of PDV to monitor community HIV risk potential., Funding: US National Institutes of Health, Elton John AIDS Foundation., Competing Interests: Declaration of interests SSS reports grants from National Institutes of Health (USA) during the conduct of the study, grants, personal fees, and non-financial support from Gilead Sciences, and grants and non-financial support from Abbott Laboratories, outside the submitted work. SHM reports personal fees from Gilead Sciences, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: In the USA, Black and Hispanic or Latinx individuals continue to be disproportionately affected by HIV. Applying a distributional cost-effectiveness framework, we estimated the cost-effectiveness and epidemiological impact of two combination implementation approaches to identify the approach that best meets the dual objectives of improving population health and reducing racial or ethnic health disparities., Methods: We adapted a dynamic, compartmental HIV transmission model to characterise HIV micro-epidemics in six US cities: Atlanta, Baltimore, Los Angeles, Miami, New York, and Seattle. We considered combinations of 16 evidence-based interventions to diagnose, treat, and prevent HIV transmission according to previously documented levels of scale-up. We then identified optimal combination strategies for each city, with the distribution of each intervention implemented according to existing service levels (proportional services approach) and the racial or ethnic distribution of new diagnoses (between Black, Hispanic or Latinx, and White or other ethnicity individuals; equity approach). We estimated total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios of strategies implemented from 2020 to 2030 (health-care perspective; 20-year time horizon; 3% annual discount rate). We estimated three measures of health inequality (between-group variance, index of disparity, Theil index), incidence rate ratios, and rate differences for the selected strategies under each approach., Findings: In all cities, optimal combination strategies under the equity approach generated more QALYs than those with proportional services, ranging from a 3·1% increase (95% credible interval [CrI] 1·4-5·3) in New York to more than double (101·9% [75·4-134·6]) in Atlanta. Compared with proportional services, the equity approach delivered lower costs over 20 years in all cities except Los Angeles; cost reductions ranged from $22·9 million (95% CrI 5·3-55·7 million) in Seattle to $579·8 million (255·4-940·5 million) in Atlanta. The equity approach also reduced incidence disparities and health inequality measures in all cities except Los Angeles., Interpretation: Equity-focused HIV combination implementation strategies that reduce disparities for Black and Hispanic or Latinx individuals can significantly improve population health, reduce costs, and drive progress towards Ending the HIV Epidemic goals in the USA., Funding: National Institute on Drug Abuse., Competing Interests: Declaration of interests KA reports grants from the US National Institutes of Health (NIH), personal fees from The All of Us Research Program (NIH), personal fees from TrioHealth, and non-financial support from Cumming School of Medicine, University of Calgary, outside the submitted work. CNB reports grants from the National Institute on Drug Abuse, during the conduct of the study. EE reports personal fees from ViiV Healthcare, outside the submitted work. KAG reports personal fees from Simon Fraser University, during the conduct of the study. SHM reports personal fees from Gilead Sciences, outside the submitted work. MG reports research support from Hologic, outside the submitted work. SAS reports grants from NIH, outside the submitted work. HT reports grants from Gilead Sciences, outside the submitted work. BN reports grants from NIH, during the conduct of the study. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Abstract: Geographic information systems (GIS) tools can be used to understand the spatial distribution of local HIV epidemics but are often underutilized, especially in low-middle income countries. We present characteristics of an HIV epidemic within Hyderabad, a large city in southern India, as a case study to highlight the utility of such data in program planning.Cross-sectional sample recruited using respondent-driven sampling in a cluster-randomized trial.We analyzed data from 2 cross-sectional respondent-driven sampling surveys of MSM in Hyderabad, which were conducted as part of a cluster-randomized trial. All participants were tested for HIV and those positive underwent viral load quantification. ArcGIS was used to create heat maps of MSM distribution using self-reported postal code of residence and combined into larger zones containing at least 200 MSM.Postal code data was available for 661 MSM (66.2%) in the baseline and 978 MSM (97.8%) in the follow-up survey. The proportion of HIV-positive MSM (12.7-15.7%) and prevalence of virally suppressed persons (2.6-8.2%) increased between the 2 surveys. The distribution of all MSM, HIV-positive MSM, and HIV-viremic MSM differed significantly by geographic zone with several zones having higher numbers of HIV-positive and viremic individuals than would be expected based on the distribution of all MSM.The prevalence of HIV and HIV viremia among MSM differed by geographic zones within a city and evolved over time. Such data could be critical to improving program implementation efficiency by accurately targeting resources to population characteristics., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: SC, AS, KZ, PD, SM, SS, PN, MK, EO, GL, CL No competing interests declared, SM reports personal fees from Gilead Sciences, outside the submitted work. SS reports grants/products and advisory board fees from Gilead Sciences and grants/products from Abbott Diagnostics, outside the submitted work., (© 2021, Clipman et al.)

Objective: People with HIV (PWH) experience increased prevalence of obstructive lung disease (OLD), regardless of greater observed smoking behaviors. We investigated whether the effect of incident OLD on mortality differed by HIV and HIV viral suppression among persons who inject drugs (PWID) and report smoking history., Design: ALIVE is a longitudinal, observational cohort study of HIV-positive and seronegative PWID. This analysis included participants who had at least one spirometry measure to assess OLD between 2007 and 2016, excluding those who never smoked (5%, n = 62) or had baseline OLD (17%, n = 269)., Methods: Incident OLD occurred when the first prebronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) less than 0.70 during follow-up. The effect of incident OLD on all-cause mortality was estimated in PWH and seronegative participants using inverse-probability-of-treatment-weighted marginal structural models controlling for baseline (age, race, sex, calendar year, smoking pack-years) and time-varying (smoking intensity, viral suppression, and calendar time) confounders., Results: Among 1204 participants, 269 (22.3%) and 157 (13.0%) experienced incident OLD and death, respectively, over a median of five person-years of follow-up. There was no effect of OLD on mortality among seronegative participants [hazard ratio = 0.84, 95% confidence interval (CI): 0.47-1.48]; however, PWH diagnosed with OLD experienced an increased mortality risk (hazard ratio = 1.71, 95% CI: 1.04-2.80) during follow-up. HIV viral suppression did not confound or modify the effect of OLD on mortality among PWH., Conclusion: There was an apparent effect of OLD on all-cause mortality irrespective of viral suppression among PWH but not among seronegative persons, after accounting for baseline and time-varying confounders. These results highlight the need for enhanced screening and management of OLD among PWH., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The latent reservoir for human immunodeficiency virus type 1 (HIV-1) in CD4+ T cells is a major barrier to cure. HIV-1-infected persons who inject drugs (PWID) often struggle to maintain suppression of viremia and experience nonstructured treatment interruptions (NTIs). The effects of injecting drugs or NTIs on the reservoir are unclear. Using the intact proviral DNA assay, we found no apparent effect of heroin or cocaine use on reservoir size. However, we found significantly larger reservoirs in those with frequent NTIs or a shorter interval from last detectable HIV RNA measurement. These results have important implications for inclusion of PWID in HIV-1 cure studies., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Widespread viral and serological testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present a unique opportunity to also test for human immunodeficiency virus (HIV) infection. We estimated the potential impact of adding linked, opt-out HIV testing alongside SARS-CoV-2 testing on the HIV incidence and the cost-effectiveness of this strategy in 6 US cities., Methods: Using a previously calibrated dynamic HIV transmission model, we constructed 3 sets of scenarios for each city: (1) sustained current levels of HIV-related treatment and prevention services (status quo); (2) temporary disruptions in health services and changes in sexual and injection risk behaviors at discrete levels between 0%-50%; and (3) linked HIV and SARS-CoV-2 testing offered to 10%-90% of the adult population in addition to Scenario 2. We estimated the cumulative number of HIV infections between 2020-2025 and the incremental cost-effectiveness ratios of linked HIV testing over 20 years., Results: In the absence of linked, opt-out HIV testing, we estimated a total of a 16.5% decrease in HIV infections between 2020-2025 in the best-case scenario (50% reduction in risk behaviors and no service disruptions), and a 9.0% increase in the worst-case scenario (no behavioral change and 50% reduction in service access). We estimated that HIV testing (offered at 10%-90% levels) could avert a total of 576-7225 (1.6%-17.2%) new infections. The intervention would require an initial investment of $20.6M-$220.7M across cities; however, the intervention would ultimately result in savings in health-care costs in each city., Conclusions: A campaign in which HIV testing is linked with SARS-CoV-2 testing could substantially reduce the HIV incidence and reduce direct and indirect health care costs attributable to HIV., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: We evaluated whether identification of undiagnosed HIV-infected people who inject drugs (PWID) via respondent-driven sampling (RDS) can be enhanced through a precision RDS (pRDS) approach., Design/methods: First, using prior RDS data from PWID in India, we built a prediction algorithm for recruiting undiagnosed HIV-infected PWID. pRDS was tested in Morinda, Punjab where participants were randomly assigned to standard or pRDS. In the standard RDS approach, all participants received two recruitment coupons. For pRDS, the algorithm determined an individual's probability of recruiting an undiagnosed PWID, and individuals received either two (low probability) or five (high probability) coupons. Efficiency in identifying undiagnosed HIV-infected PWID for the RDS approaches was evaluated in two ways: the number needed to recruit (NNR) and identification rate/week., Results: Predictors of recruiting undiagnosed PWID included HIV/HCV infection, network size, syringe services utilization, and injection environment. 1631 PWID were recruited in Morinda. From the standard RDS approach, 615 were recruited, including 39 undiagnosed; from pRDS, 1012 were recruited, including 77 undiagnosed. In pRDS, those with higher predicted probability were more likely to recruit others with HIV/HCV co-infection, undiagnosed and viremic HIV, and who utilized services. pRDS had a significantly higher identification rate of undiagnosed PWID (1.5/week) compared with the standard (0.8/week). The NNR for pRDS (13.1) was not significantly lower than the standard approach (15.8)., Conclusion: pRDS identified twice as many undiagnosed and viremic PWID significantly faster than the standard approach. Leveraging RDS or similar network-based strategies should be considered alongside other strategies to ensure meeting UNAIDS targets., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: α4β7 is a gut-homing integrin heterodimer that can act as a non-essential binding molecule for HIV. A previous study in heterosexual African women found that individuals with higher proportions of α4β7 expressing CD4 + T cells were more likely to become infected with HIV, as well as present with faster disease progression. It is unknown if this phenomenon is also observed in men who have sex with men (MSM) or people who inject drugs (PWID)., Methods: MSM and transgender women who seroconverted as part of the HVTN 505 HIV vaccine trial and PWID who seroconverted during the ALIVE cohort study were selected as cases and matched to HIV-uninfected controls from the same studies (1:1 and 1:3, respectively). Pre-seroconversion PBMC samples from cases and controls in both studies were examined by flow cytometry to measure levels of α4β7 expression on CD4 + T cells. Multivariable conditional logistic regression was used to compare α4β7 expression levels between cases and controls. A Kaplan-Meier curve was used to examine the association of α4β7 expression pre-seroconversion with HIV disease progression., Findings: In MSM and transgender women (n = 103 cases, 103 controls), there was no statistically significant difference in the levels of α4β7 expression on CD4 + T cells between cases and controls (adjusted odds ratio [adjOR] =1.10, 95% confidence interval [CI]=0.94,1.29; p = 0.246). Interestingly, in PWID (n = 49 cases, 143 controls), cases had significantly lower levels of α4β7 expression compared to their matched controls (adjOR = 0.80, 95% CI = 0.68, 0.93; p = 0.004). Among HIV-positive PWID (n = 47), there was no significant association in HIV disease progression in individuals above or below the median level of α4β7 expression (log-rank p = 0.84)., Interpretation: In contrast to findings in heterosexual women, higher α4β7 expression does not predict HIV acquisition or disease progression in PWID or MSM., Funding: This study was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. The study was also supported by extramural grants from NIAID T32AI102623 (E.U.P.), and UM1AI069470., Competing Interests: Declaration of Competing Interest Dr. Mehta reports personal fees from Gilead Sciences, outside the submitted work. No other conflicts of interest exist., (Published by Elsevier B.V.)

Objectives: In high-income countries, hazardous alcohol use is associated with reduced receipt of antiretroviral therapy (ART) and viral suppression among people living with HIV (PLHIV) who inject drugs. These associations are less understood in lower middle-income countries (LMIC) and upper middle-income countries., Design: We examined associations between hazardous alcohol use, ART receipt, and viral suppression among PLHIV who reported current or former injection drug use. Participants were from nine studies in the United States (high-income country), India (LMIC), Russia (upper middle-income country), and Vietnam (LMIC)., Methods: Hazardous alcohol use was measured via Alcohol Use Disorders Identification Test. Outcomes were HIV viral suppression (viral load of <1000 RNA copies/ml) and self-reported ART receipt. Logistic regression assessed associations between hazardous alcohol use and both outcome variables, controlling for age and sex, among participants with current and former injection drug use., Results: Among 2790 participants, 16% were women, mean age was 37.1 ± 9.5 years. Mean Alcohol Use Disorders Identification Test scores were 4.6 ± 8.1 (women) and 6.2 ± 8.3 (men); 42% reported ART receipt; 40% had viral suppression. Hazardous alcohol use was significantly associated with reduced ART receipt in India (adjusted odds ratio = 0.59, 95% confidence interval: 0.45-0.77, P < 0.001); and lower rates of viral suppression in Vietnam (adjusted odds ratio = 0.51, 95% confidence interval: 0.31-0.82, P = 0.006)., Conclusion: Associations between hazardous alcohol use, ART receipt, and viral suppression varied across settings and were strongest in LMICs. Addressing hazardous alcohol use holds promise for improving HIV continuum of care outcomes among PLHIV who inject drugs. Specific impact and intervention needs may differ by setting.

Objective: We investigated the duration of HIV transmission clusters., Design: Fifty-four individuals newly infected at enrollment in the ALIVE cohort were included, all of whom had sequences at an intake visit (T1) and from a second (T2) and/or a third (T3) follow-up visit, median 2.9 and 5.4 years later, respectively., Methods: Sequences were generated using the 454 DNA sequencing platform for portions of HIV pol and env (HXB2 positions 2717-3230; 7941-8264). Genetic distances were calculated using tn93 and sequences were clustered over a range of thresholds (1--5%) using HIV-TRACE. Analyses were performed separately for individuals with pol sequences for T1 + T2 (n = 40, 'Set 1') and T1 + T3 (n = 25; 'Set 2'), and env sequences for T1 + T2 (n = 47, 'Set 1'), and T1 + T3 (n = 30; 'Set 2')., Results: For pol, with one exception, a single cluster contained more than 75% of samples at all thresholds, and cluster composition was at least 90% concordant between time points/thresholds. For env, two major clusters (A and B) were observed at T1 and T2/T3, although cluster composition concordance between time points/thresholds was low (<60%) at lower thresholds for both sets 1 and 2. In addition, several individuals were included in clusters at T2/T3, although not at T1., Conclusion: Caution should be used in applying a single threshold in population studies where seroconversion dates are unknown. However, the retention of some clusters even after 5 + years is evidence for the robustness of the clustering approach in general.

Background: The availability of effective, oral direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment has put elimination of HCV as a public health challenge within reach. However, little is known about the characteristics of transmission networks of people who inject drugs (PWID)., Methods: Sequencing of a segment of the HCV genome was performed on samples collected from a community-based cohort of PWID between August 2005 and December 2016. Phylogenetic trees were inferred, and clusters were identified (70% bootstrap threshold; 0.04 maximum genetic distance threshold). We describe sex, race, age difference, and HIV infection status of potential transmission partners. Logistic regression was used to assess factors associated with being in an HCV cluster., Results: Of 508 HCV genotype 1 viremic PWID, 8% (n = 41) were grouped into 20 clusters, consisting of 19 pairs and 1 triad. In adjusted analyses, female sex (odds ratio [OR] 2.3 [95% confidence interval (CI) 1.2-4.5]) and HIV infection (OR 5.7 [CI 2.7-11.9]) remained independently associated with being in an HCV infection cluster., Conclusions: Molecular epidemiological analysis reveals that, in this cohort of PWID in Baltimore, HIV infection and female sex were associated with HCV clustering. Combination HCV prevention interventions targeting HIV infected PWID and addressing HCV infection prevention needs of women have potential to advance HCV elimination efforts.

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.

Background: Increased uptake of hepatitis C virus (HCV) treatment among people who inject drugs (PWID) will be critical to achieve HCV elimination goals. There are limited data on HCV treatment uptake among PWID recruited from community-based settings in the HCV direct-acting antiviral (DAA) era., Methods: We analysed data from PWID with HCV newly recruited into the Baltimore, Maryland-based AIDS Linked to the IntraVenous Experience (ALIVE) cohort between 2015 and 2018. We characterized the HCV care continuum and evaluated factors associated with HCV treatment uptake., Results: Of the 418 PWID with HCV, the median age was 49 years and most (88%) reported recent injection drug use (IDU). Overall, 23% had ever been evaluated by a provider for HCV treatment, 17% ever initiated DAA treatment and 13% were cured of HCV infection. Treatment uptake approximately doubled between 2015 and 2018 (13% to 26%, P = .01). In multivariable analyses, HIV infection (adjusted Odds Ratio [aOR] 2.5 [95% Confidence Interval (CI) 1.3, 4.8]), current employment (aOR 4.1 [CI 1.2, 14.4]), having a primary care provider (aOR 4.3 [CI 1.2, 14.9) and longer duration of IDU (aOR 1.3 [CI 1.1, 1.6]) were positively associated with HCV treatment. PWID with a lower annual income (≤$5000) were less likely to have initiated HCV treatment (aOR 0.5 [CI 0.3, 0.98])., Conclusions: Although HCV treatment uptake among PWID in this community-based setting in the DAA era remains suboptimal, it is encouraging that treatment uptake has increased in recent years. Innovative strategies are needed to reach all PWID infected with HCV., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chronic respiratory disease represents an important comorbidity for persons living with HIV (PLWH). HIV itself is associated with greater impairment in lung function. We aimed to determine the association between declining lung function and both quality of life (QOL) and health care utilization for PLWH., Methods: Using longitudinal data from the Study of HIV Infection in the Etiology of Lung Disease 2009-2017, we studied the association between changes in lung function and both QOL and acute care events (emergency department visit or hospitalization). The Medical Outcomes Studies-HIV Questionnaire provided QOL domains. Multivariable regression models were performed with generalized estimating equations accounting for 1499 participants, 485 with HIV, contributing 10,825 spirometry visits., Results: Among PLWH, decreased FEV1 was associated with worse physical health for those with higher viral load [β: -1.66, 95% confidence interval (CI): -3.11 to -0.39] compared to those with viral suppression (β: -0.58, 95% CI: -1.06 to -0.162), even in those without airflow obstruction. Lower FEV1 was also associated with increased odds of both emergency department (odds ratio: 1.21, 95% CI: 1.09 to 1.34) and inpatient (odds ratio: 1.26, 95% CI: 1.12 to 1.42) hospitalizations for PLWH. Lung function was not associated with increased odds of acute care events for HIV-uninfected participants., Conclusions: FEV1 declines represent an independent predictor of QOL and acute care events among PLWH. Although the generalizability of these results may be limited, because of the high-risk population included, findings suggest that care for PLWH should involve monitoring FEV1 over time, especially in those with poor virologic control, with emphasis on the development and implementation of interventions to mitigate lung function decline.

Background: Persons who inject drugs (PWID) are at a disproportionately high risk of HIV infection. We aimed to determine the highest-valued combination implementation strategies to reduce the burden of HIV among PWID in 6 US cities., Methods: Using a dynamic HIV transmission model calibrated for Atlanta, Baltimore, Los Angeles, Miami, New York City, and Seattle, we assessed the value of implementing combinations of evidence-based interventions at optimistic (drawn from best available evidence) or ideal (90% coverage) scale-up. We estimated reduction in HIV incidence among PWID, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) for each city (10-year implementation; 20-year horizon; 2018 $ US)., Results: Combinations that maximized health benefits contained between 6 (Atlanta and Seattle) and 12 (Miami) interventions with ICER values ranging from $94 069/QALY in Los Angeles to $146 256/QALY in Miami. These strategies reduced HIV incidence by 8.1% (credible interval [CI], 2.8%-13.2%) in Seattle and 54.4% (CI, 37.6%-73.9%) in Miami. Incidence reduction reached 16.1%-75.5% at ideal scale., Conclusions: Evidence-based interventions targeted to PWID can deliver considerable value; however, ending the HIV epidemic among PWID will require innovative implementation strategies and supporting programs to reduce social and structural barriers to care., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background & Aims: Accurate HCV incidence estimates are critical for monitoring progress towards HCV elimination goals, including an 80% reduction in HCV incidence by 2030. Moreover, incidence estimates can help guide prevention and treatment programming, particularly in the context of the US opioid epidemic., Methods: An inexpensive, Genedia-based HCV IgG antibody avidity assay was evaluated as a platform to estimate cross-sectional, population-level primary HCV incidence using 1,840 HCV antibody and RNA-positive samples from 875 individuals enrolled in 5 cohort studies in the US and India. Using samples collected <2 years following HCV seroconversion, the mean duration of recent infection (MDRI) was calculated by fitting a maximum likelihood binomial regression model to the probability of appearing recent. Among samples collected ≥2 years post-HCV seroconversion, an individual-level false recent ratio (FRR) was calculated by estimating the probability of appearing recent using an exact binomial test. Factors associated with falsely appearing recent among samples collected ≥2 years post seroconversion were determined by Poisson regression with generalized estimating equations and robust variance estimators., Results: An avidity index cut-off of <40% resulted in an MDRI of 113 days (95% CI 84-146), and FRRs of 0.4% (95% CI 0.0-1.2), 4.6% (95% CI 2.2-8.3), and 9.5% (95% CI 3.6-19.6) among individuals who were HIV-uninfected, HIV-infected, and HIV-infected with a CD4 count <200/μl, respectively. No variation was seen between HCV genotypes 1 and 3. In hypothetical scenarios of high-risk settings, a sample size of <1,000 individuals could reliably estimate primary HCV incidence., Conclusions: This cross-sectional approach can estimate primary HCV incidence for the most common genotypes. This tool can serve as a valuable resource for program and policy planners seeking to monitor and reduce HCV burden., Lay Summary: Determining the rate of new hepatitis C virus (HCV) infections in a population is critical to monitoring progress toward HCV elimination and to appropriately guide control efforts. However, since HCV infections are most often initially asymptomatic, it is difficult to estimate the rate of new HCV infections without following HCV-uninfected people over time and repeatedly testing them for HCV infection. Here, we present a novel, resource-efficient method to estimate the rate of new HCV infections in a population using data from a single timepoint., Competing Interests: Conflicts of interest The authors do not have potential conflicts of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. All rights reserved.)

Background: The HIV epidemic in the USA is a collection of diverse local microepidemics. We aimed to identify optimal combination implementation strategies of evidence-based interventions to reach 90% reduction of incidence in 10 years, in six US cities that comprise 24·1% of people living with HIV in the USA., Methods: In this economic modelling study, we used a dynamic HIV transmission model calibrated with the best available evidence on epidemiological and structural conditions for six US cities: Atlanta (GA), Baltimore (MD), Los Angeles (CA), Miami (FL), New York City (NY), and Seattle (WA). We assessed 23 040 combinations of 16 evidence-based interventions (ie, HIV prevention, testing, treatment, engagement, and re-engagement) to identify combination strategies providing the greatest health benefit while remaining cost-effective. Main outcomes included averted HIV infections, quality-adjusted life-years (QALYs), total cost (in 2018 US$), and incremental cost-effectiveness ratio (ICER; from the health-care sector perspective, 3% annual discount rate). Interventions were implemented at previously documented and ideal (90% coverage or adoption) scale-up, and sustained from 2020 to 2030, with outcomes evaluated until 2040., Findings: Optimal combination strategies providing health benefit and cost-effectiveness contained between nine (Seattle) and 13 (Miami) individual interventions. If implemented at previously documented scale-up, these strategies could reduce incidence by between 30·7% (95% credible interval 19·1-43·7; Seattle) and 50·1% (41·5-58·0; New York City) by 2030, at ICERs ranging from cost-saving in Atlanta, Baltimore, and Miami, to $95 416 per QALY in Seattle. Incidence reductions reached between 39·5% (26·3-53·8) in Seattle and 83·6% (70·8-87·0) in Baltimore at ideal implementation. Total costs of implementing strategies across the cities at previously documented scale-up reached $559 million per year in 2024; however, costs were offset by long-term reductions in new infections and delayed disease progression, with Atlanta, Baltimore, and Miami projecting cost savings over the 20 year study period., Interpretation: Evidence-based interventions can deliver substantial public health and economic value; however, complementary strategies to overcome social and structural barriers to HIV care will be required to reach national targets of the ending the HIV epidemic initiative by 2030., Funding: National Institutes of Health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Frailty is a critical aging-related syndrome marked by diminished physiologic reserve and heightened vulnerability to stress, predictive of major adverse clinical outcomes in HIV-infected and uninfected adults. Frailty is a dynamic state, yet little data exist on predictors and consequences of frailty transitions., Design/methods: Frailty was assessed semiannually among HIV-infected and uninfected persons with prior injection drug use using the five Fried phenotype domains. An inflammatory index score was constructed from IL-6 and soluble TNF-α receptor-1 data. Markov transition models assessed determinants of frailty transitions. Cox proportional hazards models estimated mortality risk., Results: Among 1353 AIDS Linked to the IntraVenous Experience participants with 9559 frailty transition assessments, 33% were HIV-infected. Younger age, higher education, employment, reduced comorbidity, HIV virologic suppression, elevated CD4 nadir (>500 cells/μl) and absence of a prior AIDS diagnosis were significantly associated with both reduced frailty progression and greater frailty recovery. Each SD decrease in inflammatory index score was associated with decreased frailty progression [odds ratio 0.78; 95% confidence interval (CI), 0.65, 0.92] and increased frailty recovery (odds ratio 1.29; 95% CI, 1.08, 1.53). Being frail at one of two consecutive visits was associated with increased mortality, compared with maintenance of a nonfrail state. Being frail at both of two consecutive visits demonstrated the highest mortality risk (hazard ratio 3.23; 95% CI, 2.1, 4.96)., Conclusion: Sustained, and to a lesser degree, intermittent frail states are associated with increased mortality. HIV virologic suppression with earlier antiretroviral therapy, reduced comorbidity, and reduced inflammation may prevent frailty progression and promote frailty recovery, consequently improving survival for persons aging with HIV and persons with prior injection drug use.