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ObjectiveWe describe the prevalence of COVID-19 vaccine uptake, substance use, and other factors associated with vaccine hesitancy among participants from nine North American cohort studies following a diverse group of individuals at risk for or living with HIV.MethodsBetween May 2021 and January 2022, participants completed a survey related to COVID-19 vaccination. Participants included those with and without substance use. Those responding as 'no' or 'undecided' to the question "Do you plan on getting the COVID-19 vaccine?" were categorized as vaccine hesitant. Differences between groups were evaluated using chi-square methods and multivariable log-binomial models were used to calculate prevalence ratios (PR) of COVID-19 vaccine hesitancy with separate models for each substance.ResultsAmong 1,696 participants, COVID-19 vaccination was deferred or declined by 16%. Vaccine hesitant participants were younger, with a greater proportion unstably housed (14.8% vs. 10.0%; p = 0.02), and not living with HIV (48.% vs. 36.6%; p

BackgroundThe 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.MethodsParticipants 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.ResultsAt 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.ConclusionPWID 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.

BackgroundMeasuring the incidence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID) is key to track progress towards elimination. We aimed to summarise global data on HIV and primary HCV incidence among PWID and associations with age and sex or gender.MethodsIn this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies among PWID by searching MEDLINE, Embase, and PsycINFO, capturing studies published between Jan 1, 2000, and Dec 12, 2022, with no language or study design restrictions. We contacted authors of identified studies for unpublished or updated data. We included studies that estimated incidence by longitudinally re-testing people at risk of infection or by using assays for recent infection. We pooled incidence and relative risk (RR; young [generally defined as ≤25 years] vs older PWID; women vs men) estimates using random-effects meta-analysis and assessed risk of bias with a modified Newcastle-Ottawa scale. This study is registered with PROSPERO, CRD42020220884.FindingsOur updated search identified 9493 publications, of which 211 were eligible for full-text review. An additional 377 full-text records from our existing database and five records identified through cross-referencing were assessed. Including 28 unpublished records, 125 records met the inclusion criteria. We identified 64 estimates of HIV incidence (30 from high-income countries [HICs] and 34 from low-income or middle-income countries [LMICs]) and 66 estimates of HCV incidence (52 from HICs and 14 from LMICs). 41 (64%) of 64 HIV and 42 (64%) of 66 HCV estimates were from single cities rather than being multi-city or nationwide. Estimates were measured over 1987-2021 for HIV and 1992-2021 for HCV. Pooled HIV incidence was 1·7 per 100 person-years (95% CI 1·3-2·3; I2=98·4%) and pooled HCV incidence was 12·1 per 100 person-years (10·0-14·6; I2=97·2%). Young PWID had a greater risk of HIV (RR 1·5, 95% CI 1·2-1·8; I2=66·9%) and HCV (1·5, 1·3-1·8; I2=70·6%) acquisition than older PWID. Women had a greater risk of HIV (RR 1·4, 95% CI 1·1-1·6; I2=55·3%) and HCV (1·2, 1·1-1·3; I2=43·3%) acquisition than men. For both HIV and HCV, the median risk-of-bias score was 6 (IQR 6-7), indicating moderate risk.InterpretationAlthough sparse, available HIV and HCV incidence estimates offer insights into global levels of HIV and HCV transmission among PWID. Intensified efforts are needed to keep track of the HIV and HCV epidemics among PWID and to expand access to age-appropriate and gender-appropriate prevention services that serve young PWID and women who inject drugs.FundingCanadian Institutes of Health Research, Fonds de recherche du Québec-Santé, Canadian Network on Hepatitis C, UK National Institute for Health and Care Research, and WHO.

BackgroundThe COVID-19 pandemic has compounded the longstanding drug poisoning crisis in Canada and the United States (US). Research is needed to understand the contributions of COVID-19 and subsequent infection control measures. We sought to estimate the prevalence of and factors associated with nonfatal overdose among participants in nine prospective cohorts of people who use unregulated drugs (PWUD) in Canada and the US.MethodsData were derived from nine cohorts of PWUD in urban centres in Canada (Vancouver, BC) and the US (Baltimore, MD; Miami, FL; Chicago, IL; Los Angeles, CA) between May, 2020 and April, 2021. Multivariable logistic regression was used to identify factors associated with nonfatal overdose among participants who used unregulated drugs in the past month.ResultsAmong 885 participants (including 253 females), 41 (4.6 %) experienced a non-fatal overdose in the past month, and 453 (51.2 %) reported being highly impacted day-to-day by the pandemic. In multivariable analyses, people who experienced a non-fatal overdose were more likely to be female (Adjusted Odds Ratio [AOR]=2.18;95 % Confidence Interval [CI]=1.10-4.30); unstably housed/homeless (AOR=2.16;95 % CI=1.11-4.26); engaged in medications for opioid use disorder (AOR=2.45;95 % CI=1.19-4.97); and highly impacted day-to-day (AOR=2.42;95 % CI=1.22-5.10).ConclusionOur findings may reflect characteristics of participants who experienced a compounding of vulnerabilities during the pandemic and thus are vulnerable to overdose, including women, those unstably housed/homeless, and those who perceived their daily lives were highly impacted by the pandemic. Multi-level interventions are needed to remediate the vulnerabilities and address the main driver of poisoning crisis.

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.

BackgroundThe 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.MethodsFrom 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.ResultsThirteen 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.ConclusionsSocial 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.

BackgroundThis study examines individual-level factors associated with avoiding two important health services for people who use drugs-medications for treatment of opioid use disorder and syringe service programs-during the first year of the COVID-19 pandemic.MethodsData come from two subsamples of people who use drugs who were active participants in one of nine cohort studies in Vancouver, British Columbia; Baltimore, Maryland; Los Angeles, California; Chicago, Illinois; and Miami, Florida. Participants were interviewed remotely about COVID-19-associated disruptions to healthcare. We estimated the association of demographic, social, and health factors with each outcome using logistic regression among 702 participants (medication analysis) and 304 participants (syringe service analysis.) Analyses were repeated, stratified by city of residence, to examine geographic variation in risk.ResultsThere were large differences between cities in the prevalence of avoiding picking up medications for opioid use disorder, with almost no avoidance in Vancouver (3%) and nearly universal avoidance in Los Angeles, Chicago, and Miami (>90%). After accounting for between-city differences, no individual factors were associated with avoiding picking up medications. The only factor significantly associated with avoiding syringe service programs was higher levels of self-reported worry about COVID-19.ConclusionDuring the first year of the COVID-19 pandemic, geographic differences in service and policy contexts likely influenced avoidance of health and harm reduction services by people who use drugs in the United States and Canada more than individual differences between people.

: 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., INTRODUCTION Globally, infectious disease programmes have ambitious targets to achieve epidemic control or elimination. UNAIDS has established 95‐95‐95 targets for HIV wherein 95% of people living with HIV (PLHIV) are [...]

: 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., INTRODUCTION Globally, injection drug use drives some of the fastest‐growing HIV epidemics [1]. The National AIDS Control Organization (NACO) in India estimates that 9.3% of people who inject drugs (PWID) [...]

BackgroundUnderstanding 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.MethodsWe 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.ResultsIndividuals 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.ConclusionThese 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.

Spontaneous clearance of acute hepatitis C virus (HCV) infection is associated with single nucleotide polymorphisms (SNPs) on the MHC class II. We fine-mapped the MHC region in European (n = 1,600; 594 HCV clearance/1,006 HCV persistence) and African (n = 1,869; 340 HCV clearance/1,529 HCV persistence) ancestry individuals and evaluated HCV peptide binding affinity of classical alleles. In both populations, HLA-DQβ1Leu26 (p valueMeta = 1.24 × 10-14) located in pocket 4 was negatively associated with HCV spontaneous clearance and HLA-DQβ1Pro55 (p valueMeta = 8.23 × 10-11) located in the peptide binding region was positively associated, independently of HLA-DQβ1Leu26. These two amino acids are not in linkage disequilibrium (r2 < 0.1) and explain the SNPs and classical allele associations represented by rs2647011, rs9274711, HLA-DQB1∗03:01, and HLA-DRB1∗01:01. Additionally, HCV persistence classical alleles tagged by HLA-DQβ1Leu26 had fewer HCV binding epitopes and lower predicted binding affinities compared to clearance alleles (geometric mean of combined IC50 nM of persistence versus clearance; 2,321 nM versus 761.7 nM, p value = 1.35 × 10-38). In summary, MHC class II fine-mapping revealed key amino acids in HLA-DQβ1 explaining allelic and SNP associations with HCV outcomes. This mechanistic advance in understanding of natural recovery and immunogenetics of HCV might set the stage for much needed enhancement and design of vaccine to promote spontaneous clearance of HCV infection.

ObjectiveThe 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.MethodsThis 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.ResultsA 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.ConclusionsPsychological 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.

BackgroundIn 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.MethodsWe 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.FindingsIn 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.InterpretationEquity-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.FundingNational Institute on Drug Abuse.

BackgroundSpontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors.MethodsTo identify sex-specific genetic loci, we studied 4423 HCV-infected individuals (2903 male, 1520 female) of European, African, and Hispanic ancestry. We performed autosomal, and X chromosome sex-stratified and combined association analyses in each ancestry group.ResultsA male-specific region near the adenosine diphosphate-ribosylation factor-like 5B (ARL5B) gene was identified. Individuals with the C allele of rs76398191 were about 30% more likely to have chronic HCV infection than individuals with the T allele (OR, 0.69; P = 1.98 × 10-07), and this was not seen in females. The ARL5B gene encodes an interferon-stimulated gene that inhibits immune response to double-stranded RNA viruses. We also identified suggestive associations near septin 6 and ribosomal protein L39 genes on the X chromosome. In box sexes, allele G of rs12852885 was associated with a 40% increase in HCV clearance compared with the A allele (OR, 1.4; P = 2.46 × 10-06). Septin 6 facilitates HCV replication via interaction with the HCV NS5b protein, and ribosomal protein L39 acts as an HCV core interactor.ConclusionsThese novel gene associations support differential mechanisms of HCV clearance between the sexes and provide biological targets for treatment or vaccine development.

BackgroundWidespread 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.MethodsUsing 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.ResultsIn 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.ConclusionsA 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.

BackgroundPeople who inject drugs (PWID) are at increased risk for HIV and hepatitis C virus (HCV) infection and also have high levels of homelessness and unstable housing. We assessed whether homelessness or unstable housing is associated with an increased risk of HIV or HCV acquisition among PWID compared with PWID who are not homeless or are stably housed.MethodsIn this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies published between Jan 1, 2000, and June 13, 2017. Using the same strategy as for this existing database, we searched MEDLINE, Embase, and PsycINFO for studies, including conference abstracts, published between June 13, 2017, and Sept 14, 2020, that estimated HIV or HCV incidence, or both, among community-recruited PWID. We only included studies reporting original results without restrictions to study design or language. We contacted authors of studies that reported HIV or HCV incidence, or both, but did not report on an association with homelessness or unstable housing, to request crude data and, where possible, adjusted effect estimates. We extracted effect estimates and pooled data using random-effects meta-analyses to quantify the associations between recent (current or within the past year) homelessness or unstable housing compared with not recent homelessness or unstable housing, and risk of HIV or HCV acquisition. We assessed risk of bias using the Newcastle-Ottawa Scale and between-study heterogeneity using the I2 statistic and p value for heterogeneity.FindingsWe identified 14 351 references in our database search, of which 392 were subjected to full-text review alongside 277 studies from our existing database. Of these studies, 55 studies met inclusion criteria. We contacted the authors of 227 studies that reported HIV or HCV incidence in PWID but did not report association with the exposure of interest and obtained 48 unpublished estimates from 21 studies. After removal of duplicate data, we included 37 studies with 70 estimates (26 for HIV; 44 for HCV). Studies originated from 16 countries including in North America, Europe, Australia, east Africa, and Asia. Pooling unadjusted estimates, recent homelessness or unstable housing was associated with an increased risk of acquiring HIV (crude relative risk [cRR] 1·55 [95% CI 1·23-1·95; p=0·0002]; I2= 62·7%; n=17) and HCV (1·65 [1·44-1·90; p

We estimated human immunodeficiency virus incidence and incidence rate ratios (IRRs) for black and Hispanic vs white populations in 6 cities in the United States (2020-2030). Large reductions in incidence are possible, but without elimination of disparities in healthcare access, we found that wide disparities persisted for black compared with white populations in particular (lowest IRR, 1.69 [95% credible interval, 1.19-2.30]).

ObjectivesIn 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.DesignWe 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).MethodsHazardous alcohol use was measured via Alcohol Use Disorders Identification Test. Outcomes were HIV viral suppression (viral load of

Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible causal variants that may contribute to HCV clearance. First, we performed sequencing of IFNL1-IFNL4 region in 64 individuals sampled according to rs368234815 genotype: TT/clearance (N = 16) and ΔG/persistent (N = 15) (genotype-outcome concordant) or TT/persistent (N = 19) and ΔG/clearance (N = 14) (discordant). 25 SNPs had a difference in counts of alternative allele >5 between clearance and persistence individuals. Then, we evaluated those markers in an association analysis of HCV clearance conditioning on rs368234815 in two groups of European (692 clearance/1 025 persistence) and African ancestry (320 clearance/1 515 persistence) individuals. 10/25 variants were associated (P

BackgroundPersons 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.MethodsUsing 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).ResultsCombinations 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.ConclusionsEvidence-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.

BackgroundThe 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.MethodsIn 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.FindingsOptimal 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.InterpretationEvidence-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.FundingNational Institutes of Health.

Background. Heterogeneity in HIV microepidemics across US cities necessitates locally oriented, combination implementation strategies to prioritize resources. We calibrated and validated a dynamic, compartmental HIV transmission model to establish a status quo treatment scenario, holding constant current levels of care for 6 US cities. Methods. Built off a comprehensive evidence synthesis, we adapted and extended a previously published model to replicate the transmission, progression, and clinical care for each microepidemic. We identified a common set of 17 calibration targets between 2012 and 2015 and used the Morris method to select the most influential parameters for calibration. We then applied the Nelder-Mead algorithm to iteratively calibrate the model to generate 2000 best-fitting parameter sets. Finally, model projections were internally validated with a series of robustness checks and externally validated against published estimates of HIV incidence, while the face validity of 25-year projections was assessed by a Scientific Advisory Committee (SAC). Results. We documented our process for model development, calibration, and validation to maximize its transparency and reproducibility. The projected outcomes demonstrated a good fit to calibration targets, with a mean goodness-of-fit ranging from 0.0174 (New York City [NYC]) to 0.0861 (Atlanta). Most of the incidence predictions were within the uncertainty range for 5 of the 6 cities (ranging from 21% [Miami] to 100% [NYC]), demonstrating good external validity. The face validity of the long-term projections was confirmed by our SAC, showing that the incidence would decrease or remain stable in Atlanta, Los Angeles, NYC, and Seattle while increasing in Baltimore and Miami. Discussion. This exercise provides a basis for assessing the incremental value of further investments in HIV combination implementation strategies tailored to urban HIV microepidemics.

We estimated 10-year (2020-2030) trajectories for human immunodeficiency virus incidence in 6 US cities. Estimated incidence will only decrease in 2 of 6 cities, with the overall population-weighted incidence decreasing 3.1% (95% credible interval [CrI], -1.0% to 8.5%) by 2025, and 4.3% (95% CrI, -2.6% to 12.7%) by 2030 across cities. Targeted, context-specific combination implementation strategies will be necessary to meet the newly established national targets.