Faculty Bibliography

BACKGROUND:New diagnoses of HIV-1 infection among people who inject drugs (PWID) in Athens, Greece, saw a significant increase in 2011 and a subsequent decline after 2013. Despite this, ongoing HIV-1 transmission persisted from 2014 to 2020 within this population. Our objective was to estimate the time of infection for PWID in Athens following the HIV-1 outbreak, explore the patterns of HIV-1 dispersal over time, and determine the duration from infection to diagnosis. METHODS:Time from HIV-1 infection to diagnosis was estimated for 844 individuals infected within 4 PWID-specific clusters and for 8 PWID infected with sub-subtype A6 diagnosed during 2010-2019. Phylogeny reconstruction was performed using the maximum-likelihood method. HIV-1 infection dates were based on molecular clock calculations. RESULTS:In total 86 of 92 (93.5%) sequences from PWID diagnosed during 2016-2019 were either related to the previously identified PWID-specific clusters (n = 81) or belonged to a new A6 cluster (n = 5). The median time between infection and diagnosis was 0.42 years during the outbreak period and 0.70 years during 2016-2019 (p < 0.001). The proportion of clustered sequences from PWID was very low at 5.3% during the pre-outbreak period (1998-2009), saw an increase to 41.7% one year before the outbreak in 2010, and consistently remained high during the whole period after 2011, spanning the post-outbreak period (2016-2019) with a range from 92.9% to 100%. CONCLUSIONS:The substantial proportion of clustered infections (93.5%) during 2016-2019 implies a persistent 'slow burn' HIV outbreak among PWID in Athens, suggesting that the outbreak was not successfully eliminated. The consistently high proportion of clustered sequences since the onset of the outbreak suggests the persistence of ongoing HIV-1 transmission attributed to injection practices. Our findings underscore the importance of targeted interventions among PWID, considering the ongoing transmission rate and prolonged time from infection to diagnosis.

The U.S. population has suffered worse health consequences owing to COVID-19 than comparable wealthy nations. COVID-19 had caused more than 1.1 million deaths in the U.S. as of May 2023 and contributed to a 3-year decline in life expectancy. A coalition of public health workers and community activists launched an external review of the Centers for Disease Control and Prevention's pandemic management from January 2021 to May 2023. The authors used a modified Delphi process to identify core pandemic management areas, which formed the basis for a survey and literature review. Their analysis yields 3 overarching shortcomings of the Centers for Disease Control and Prevention's pandemic management: (1) Centers for Disease Control and Prevention leadership downplays the serious impacts and aerosol transmission risks of COVID-19, (2) Centers for Disease Control and Prevention leadership has aligned public guidance with commercial and political interests over scientific evidence, and (3) Centers for Disease Control and Prevention guidance focuses on individual choice rather than emphasizing prevention and equity. Instead, the agency must partner with communities most impacted by the pandemic and encourage people to protect one another using layered protections to decrease COVID-19 transmission. Because emerging variants can already evade existing vaccines and treatments and Long COVID can be disabling and lacks definitive treatment, multifaceted, sustainable approaches to the COVID-19 pandemic are essential to protect people, the economy, and future generations.

We sought to disentangle effects of the components of a peer-education intervention on self-reported injection risk behaviors among people who inject drugs (n = 560) in Philadelphia, US. We examined 226 egocentric groups/networks randomized to receive (or not) the intervention. Peer-education training consisted of two components delivered to the intervention network index individual only: (1) an initial training and (2) "booster" training sessions during 6- and 12-month follow up visits. In this secondary data analysis, using inverse-probability-weighted log-binomial mixed effects models, we estimated the effects of the components of the network-level peer-education intervention upon subsequent risk behaviors. This included contrasting outcome rates if a participant is a network member [non-index] under the network exposure versus under the network control condition (i.e., spillover effects). We found that compared to control networks, among intervention networks, the overall rates of injection risk behaviors were lower in both those recently exposed (i.e., at the prior visit) to a booster (rate ratio [95% confidence interval]: 0.61 [0.46-0.82]) and those not recently exposed to it (0.81 [0.67-0.98]). Only the boosters had statistically significant spillover effects (e.g., 0.59 [0.41-0.86] for recent exposure). Thus, both intervention components reduced injection risk behaviors with evidence of spillover effects for the boosters. Spillover should be assessed for an intervention that has an observable behavioral measure. Efforts to fully understand the impact of peer education should include routine evaluation of spillover effects. To maximize impact, boosters can be provided along with strategies to recruit especially committed peer educators and to increase attendance at trainings. Clinical Trials Registration Clinicaltrials.gov NCT00038688 June 5, 2002.

Locating undiagnosed HIV infections is important for limiting transmission. However, there is limited evidence about how best to do so. In South Africa, men have been particularly challenging to reach for HIV testing due, in part, to stigma. We pilot-tested two versions of a network-based case-finding and care-linkage intervention. The first, TRIP, asked "seeds" (original participants) to recruit their sexual and/or injection partners. The second, TRIPLE, aimed to circumvent some stigma-related issues by asking seeds to recruit anyone they know who might be at risk of being HIV-positive-unaware. We recruited 11 (18% male) newly diagnosed HIV-positive (NDP) seeds from two clinics in KwaZulu-Natal, South Africa and randomly assigned them to either TRIP or TRIPLE. Network members were recruited two steps from each seed. The TRIP arm recruited 12 network members; the TRIPLE arm recruited 62. Both arms recruited NDPs at higher rates than local clinic testing, with TRIP (50.0%) outperforming (p = 0.012) TRIPLE (14.5%). However, TRIPLE (53.2%) was far superior to clinics (27.8%) and to TRIP (25.0%) at recruiting men. Given challenges around testing and treating men for HIV in this context, these findings suggest that the TRIPLE expanded network-tracing approach should be tested formally among larger samples in multiple settings.

Evaluating causal effects in the presence of interference is challenging in network-based studies of hard-to-reach populations. Like many such populations, people who inject drugs (PWID) are embedded in social networks and often exert influence on others in their network. In our setting, the study design is observational with a non-randomized network-based HIV prevention intervention. Information is available on each participant and their connections that confer possible HIV risk through injection and sexual behaviors. We considered two inverse probability weighted (IPW) estimators to quantify the population-level spillover effects of non-randomized interventions on subsequent health outcomes. We demonstrated that these two IPW estimators are consistent, asymptotically normal, and derived a closed-form estimator for the asymptotic variance, while allowing for overlapping interference sets (groups of individuals in which the interference is assumed possible). A simulation study was conducted to evaluate the finite-sample performance of the estimators. We analyzed data from the Transmission Reduction Intervention Project, which ascertained a network of PWID and their contacts in Athens, Greece, from 2013 to 2015. We evaluated the effects of community alerts on subsequent HIV risk behavior in this observed network, where the connections or links between participants were defined by using substances or having unprotected sex together. In the study, community alerts were distributed to inform people of recent HIV infections among individuals in close proximity in the observed network. The estimates of the risk differences for spillover using either IPW estimator demonstrated a protective effect. The results suggest that HIV risk behavior could be mitigated by exposure to a community alert when an increased risk of HIV is detected in the network.

Researchers across a wide array of disciplines are interested in finding the most influential subjects in a network. In a network setting, intervention effects and health outcomes can spill over from one node to another through network ties, and influential subjects are expected to have a greater impact than others. For this reason, network research in public health has attempted to maximize health and behavioral changes by intervening on a subset of influential subjects. Although influence is often defined only implicitly in most of the literature, the operative notion of influence is inherently causal in many cases: influential subjects are those we should intervene on to achieve the greatest overall effect across the entire network. In this work, we define a causal notion of influence using potential outcomes. We review existing influence measures, such as node centrality, that largely rely on the particular features of the network structure and/or on certain diffusion models that predict the pattern of information or diseases spreads through network ties. We provide simulation studies to demonstrate when popular centrality measures can agree with our causal measure of influence. As an illustrative example, we apply several popular centrality measures to the HIV risk network in the Transmission Reduction Intervention Project and demonstrate the assumptions under which each centrality can represent the causal influence of each participant in the study.

The Russian war in Ukraine poses many risks for the spread of HIV, TB and associated conditions, including possible increases in the numbers of people who inject drugs or engage in sex work in the years ahead. Ukrainian civil society and volunteer efforts have been able to maintain and at times expand services for HIV Key Populations. The extent of mutual-aid and volunteer efforts as well as the continued strength and vitality of harm reduction organizations such as the Alliance for Public Health and the rest of civil society will be crucial resources for postwar efforts to assist Key Populations and prevent the spread of HIV, TB and other diseases. The postwar period will pose great economic and political difficulties for Ukrainians, including large populations of people physically and/or psychically damaged and in pain who might become people who inject drugs. Local and international support for public health and for harm reduction will be needed to prevent potentially large-scale increases in infectious disease and related mortality.

The AIDS and COVID-19 pandemics demonstrated that nations at similar economic development levels varied widely in their capacity to protect the health of their residents. For AIDS, Britain and Australia brought gay representatives into official counsels and adopted harm reduction far more rapidly than the United States or Spain, and East African countries responded more effectively than South Africa or the Democratic Republic of the Congo. National responses to COVID-19 varied widely, with New Zealand, China, and Vietnam more effective than Italy, Brazil, or the United States. Further, as phylogenetic research has demonstrated, these pandemics spread from one country to another, with those that responded poorly acting as sources for mutations and potentially sources of transmission to countries with more effective responses. Many observers expressed surprise at the poor responses of the United States to COVID-19, but in retrospect the cutbacks in public health funding at state and national levels made it clear that this was a predictable weakness even in addition to the political vacillations that crippled the US and Brazilian responses. In a time of global sociopolitical and climate instability, it is important to measure and conduct research into spatial and time variations in 1. public health and medical funding, 2. social influence networks, social cohesion and trust, and stigmatization, 3. income inequality, 4. social conflict, and 5. other factors that affect responsiveness to pandemics.

IMPORTANCE:People who use drugs (PWUD) continue to be at risk of HIV infection, but the frequency and distribution of transmission-associated behaviors within various rural communities is poorly understood. OBJECTIVE:To examine the association of characteristics of rural PWUD with HIV transmission behaviors. DESIGN, SETTING, AND PARTICIPANTS:In this cross-sectional study, surveys of PWUD in rural communities in 10 states (Illinois, Kentucky, New Hampshire, Massachusetts, North Carolina, Ohio, Oregon, Vermont, West Virginia, and Wisconsin) were collected January 2018 through March 2020 and analyzed August through December 2022. A chain-referral sampling strategy identified convenience sample seeds who referred others who used drugs. Rural PWUD who reported any past 30-day injection drug use or noninjection opioid use "to get high" were included. EXPOSURES:Individual characteristics, including age, race, gender identity, sexual orientation, partnership status, drug of choice, and location, were collected. MAIN OUTCOMES AND MEASURES:Past 30-day frequency of behaviors associated with HIV transmission, including drug injection, syringe sharing, opposite- and same-gender partners, transactional sex, and condomless sex, was assessed. RESULTS:Of 3048 rural PWUD (mean [SD] age, 36.1 [10.3] years; 225 American Indian [7.4%], 96 Black [3.2%], and 2576 White [84.5%] among 3045 with responses; and 1737 men [57.0%] among 3046 with responses), most participants were heterosexual (1771 individuals [86.8%] among 2040 with responses) and single (1974 individuals [68.6%] among 2879 with responses). Opioids and stimulants were reported as drug of choice by 1636 individuals (53.9%) and 1258 individuals (41.5%), respectively, among 3033 individuals with responses. Most participants reported recent injection (2587 of 3046 individuals [84.9%] with responses) and condomless sex (1406 of 1757 individuals [80.0%] with responses), among whom 904 of 1391 individuals (65.0%) with responses indicated that it occurred with people who inject drugs. Syringe sharing (1016 of 2433 individuals [41.8%] with responses) and transactional sex (230 of 1799 individuals [12.8%] with responses) were reported less frequently. All characteristics and behaviors, except the number of men partners reported by women, varied significantly across locations (eg, mean [SD] age ranged from 34.5 [10.0] years in Wisconsin to 39.7 [11.0] years in Illinois; P < .001). In multivariable modeling, younger age (adjusted odds ratio [aOR] for ages 15-33 vs ≥34 years, 1.36; 95% CI, 1.08-1.72) and being single (aOR, 1.37; 95% CI, 1.08-1.74) were associated with recent injection; younger age (aOR, 1.49; 95% CI, 1.20-1.85) and bisexual orientation (aOR vs heterosexual orientation, 2.27; 95% CI, 1.60-3.23) with syringe sharing; gender identity as a woman (aOR vs gender identity as a man, 1.46; 95% CI, 1.01-2.12), bisexual orientation (aOR vs heterosexual orientation, 2.59; 95% CI, 1.67-4.03), and being single (aOR, 1.71; 95% CI, 1.15-2.55) with transactional sex; and bisexual orientation (aOR vs heterosexual orientation, 1.60; 95% CI, 1.04-2.46) and stimulants as the drug of choice (aOR vs opioids, 1.45; 95 CI, 1.09-1.93) with condomless sex with someone who injects drugs. CONCLUSIONS AND RELEVANCE:This study found that behaviors associated with HIV transmission were common and varied across communities. These findings suggest that interventions to reduce HIV risk among rural PWUD may need to be tailored to locally relevant factors.

INTRODUCTION:Rates of illicit opioid use are particularly high among young adults, yet research on overdose experience and factors associated with overdose in this population remains limited. This study examines the experiences and correlates of non-fatal overdose among young adults using illicit opioids in New York City (NYC). METHODS:539 participants were recruited via Respondent-Driven Sampling in 2014-2016. Eligibility criteria included: aged 18-29 years old; current residence in NYC; and nonmedical prescription opioid (PO) use and/or heroin use in the past 30 days. Participants completed structured interviews to assess their socio-demographics, drug use trajectories, current substance use and lifetime and most recent overdose experiences, and were tested on-site for hepatitis C virus (HCV) antibodies. RESULTS:43.9% of participants reported lifetime overdose experience; of these, 58.8% had experienced two or more overdose events. The majority of participants' most recent overdoses (63.5%) were due to polysubstance use. In bivariable analyses, after RDS adjustment, having ever overdosed was correlated with: household income of >$100,00 growing up (vs. $51,000-100,000); lifetime homelessness; HCV antibody-positive status; lifetime engagement in regular nonmedical benzodiazepine use, regular heroin injection and regular PO injection; and using a non-sterile syringe in the past 12 months. Multivariable logistic regression identified childhood household income >$100,00 (AOR=1.88), HCV-positive status (AOR=2.64), benzodiazepine use (AOR=2.15), PO injection (AOR=1.96) and non-sterile syringe use (AOR=1.70) as significant independent correlates of lifetime overdose. A multivariable model with multiple overdoses (vs. one) found only lifetime regular heroin use and PO injection to be strong correlates. DISCUSSION:Results indicate a high prevalence of lifetime and repeated overdose among opioid-using young adults in NYC, highlighting a need for intensified overdose prevention efforts for this population. The strong associations of HCV and indices of polydrug use with overdose suggest that prevention efforts should address the complex risk environment in which overdose occurs, attending to the overlapping nature of disease-related risk behavior and overdose risk behavior among young people who inject opioids. Overdose prevention efforts tailored for this group may find it useful to adopt a syndemic conception of overdose that understands such events as resulting from multiple, and often interrelated, risk factors.