Faculty Bibliography

As part of a network study of HIV infection among people who inject drugs (PWID) and their contacts, we discovered a connected subcomponent of 29 uninfected PWID. In the context of a just-declining large epidemic outbreak, this raised a question: What explains the existence of large pockets of uninfected people? Possible explanations include "firewall effects" (Friedman et al., 2000; Dombrowski et al., 2017) wherein the only HIV+ people that the uninfected take risks with have low viral loads; "bottleneck effects" wherein few network paths into the pocket of non-infection exist; low levels of risk behavior; and an impending outbreak. We considered each of these. Participants provided information on their enhanced sexual and injection networks and assisted us in recruiting network members. The largest connected component had 241 members. Data on risk behaviors in the last 6 months were collected at the individual level. Recent infection was determined by LAg (Sedia^TM Biosciences Corporation), data on recent seronegative tests, and viral load. HIV RNA was quantified using Artus HI Virus-1 RG RT-PCR (Qiagen). The 29 members of the connected subcomponent of uninfected participants were connected (network distance = 1) to 17 recently-infected and 24 long-term infected participants. Fourteen (48%) of these 29 uninfected were classified as "extremely high risk" because they self-reported syringe sharing and had at least one injection partner with viral load >100,000 copies/mL who also reported syringe sharing. Seventeen of the 29 uninfected were re-interviewed after 6 months, but none had seroconverted. These findings show the power of network research in discovering infection patterns that standard individual-level studies cannot. Theoretical development and exploratory network research studies may be needed to understand these findings and deepen our understanding of how HIV does and does not spread through communities. Finally, the methods developed here provide practical tools to study "bottleneck" and "firewall" network hypotheses in practice.

PURPOSE:This paper presents an overview of different kinds of risk and social network methods and the kinds of research questions each can address. RECENT FINDINGS:It also reviews what network research has discovered about how network characteristics are associated with HIV and other infections, risk behaviors, preventive behaviors, and care, and discusses some ways in which network-based public health interventions have been conducted. Based on this, risk and social network research and interventions seem both feasible and valuable for addressing the many public health and social problems raised by the widespread use of opioids in the US South.

Background/UNASSIGNED:The Transmission Reduction Intervention Project (TRIP) is a network-based intervention that aims at decreasing human immunodeficiency virus type 1 (HIV-1) spread. We herein explore associations between transmission links as estimated by phylogenetic analyses, and social network-based ties among persons who inject drugs (PWID) recruited in TRIP. Methods/UNASSIGNED:Phylogenetic trees were inferred from HIV-1 sequences of TRIP participants. Highly supported phylogenetic clusters (transmission clusters) were those fulfilling 3 different phylogenetic confidence criteria. Social network-based ties (injecting or sexual partners, same venue engagement) were determined based on personal interviews, recruitment links, and field observation. Results/UNASSIGNED:TRIP recruited 356 individuals (90.2% PWID) including HIV-negative controls; recently HIV-infected seeds; long-term HIV-infected seeds; and their social network members. Of the 150 HIV-infected participants, 118 (78.7%) were phylogenetically analyzed. Phylogenetic analyses suggested the existence of 13 transmission clusters with 32 sequences. Seven of these clusters included 14 individuals (14/32 [43.8%]) who also had social ties with at least 1 member of their cluster. This proportion was significantly higher than what was expected by chance. Conclusions/UNASSIGNED:Molecular methods can identify HIV-infected people socially linked with another person in about half of the phylogenetic clusters. This could help public health efforts to locate individuals in networks with high transmission rates.

Given globalization and other social phenomena, controlling the spread of infectious diseases has become an imperative public health priority. A plethora of interventions that in theory can mitigate the spread of pathogens have been proposed and applied. Evaluating the effectiveness of such interventions is costly and in many circumstances unrealistic. Most important, the community effect (i.e., the ability of the intervention to minimize the spread of the pathogen from people who received the intervention to other community members) can rarely be evaluated. Here we propose a study design that can build and evaluate evidence in support of the community effect of an intervention. The approach exploits molecular evolutionary dynamics of pathogens in order to track new infections as having arisen from either a control or an intervention group. It enables us to evaluate whether an intervention reduces the number and length of new transmission chains in comparison with a control condition, and thus lets us estimate the relative decrease in new infections in the community due to the intervention. We provide as an example one working scenario of a way the approach can be applied with a simulation study and associated power calculations.

BACKGROUND:TRIP (Transmission Reduction Intervention Project) was a network-based, contact tracing approach to locate and link to care, mostly people who inject drugs (PWID) with recent HIV infection. OBJECTIVE:We investigated whether sequences from HIV-infected participants with high viral load cluster together more frequently than what is expected by chance. METHODS:Paired end reads were generated for 104 samples using Illumina MiSeq next-generation sequencing. RESULTS:63 sequences belonged to previously identified local transmission networks of PWID (LTNs) of an HIV outbreak in Athens, Greece. For two HIV-RNA cut-offs (105 and 106 IU/mL), HIV transmissions were more likely between PWID with similar levels of HIV-RNA (p<0.001). 10 of the 14 sequences (71.4%) from PWID with HIV-RNA >106 IU/mL were clustered in 5 pairs. For 4 of these clusters (80%), there was in each one of them at least one sequence from a recently HIVinfected PWID. CONCLUSION:We showed that transmissions are more likely among PWID with high viremia.

OBJECTIVES/OBJECTIVE:To estimate the effect of California's prescription drug monitoring program's (PDMP) registration mandate on use of the PDMP. METHODS:We evaluated the effect of California's mandatory PDMP registration law by fitting time series models on the percentage of clinicians registered for California's PDMP and the percentage of clinicians who were active PDMP users (users who created ≥ 1 patient prescription reports in a given month) from 2010 through 2017. We also compared PDMP use among early PDMP adopters (clinicians who registered > 8 months before the mandatory registration deadline) versus late adopters (clinicians who registered ≤ 8 months before the deadline). RESULTS:Mandatory registration was associated with increases in active PDMP users: 53.5% increase for prescribers and 17.9% for pharmacists. Early adopters were 4 times more likely to be active PDMP users than were late adopters. CONCLUSIONS:Mandatory registration was associated with increases in PDMP registration and use, but most new registrants did not become active users. Public Health Implications. Mandatory PDMP registration increases PDMP use but does not result in widespread PDMP usage by all clinicians prescribing controlled substances.

Background/UNASSIGNED:Despite insufficient evidence regarding its risks and benefits, marijuana is increasingly available and is aggressively marketed to the public. Objective/UNASSIGNED:To understand the public's views on the risks and benefits of marijuana use. Design/UNASSIGNED:Probability-based online survey. Setting/UNASSIGNED:United States, 2017. Participants/UNASSIGNED:16 280 U.S. adults. Measurements/UNASSIGNED:Proportion of U.S. adults who agreed with a statement. Results/UNASSIGNED:The response rate was 55.3% (n = 9003). Approximately 14.6% of U.S. adults reported using marijuana in the past year. About 81% of U.S. adults believe marijuana has at least 1 benefit, whereas 17% believe it has no benefit. The most common benefit cited was pain management (66%), followed by treatment of diseases, such as epilepsy and multiple sclerosis (48%), and relief from anxiety, stress, and depression (47%). About 91% of U.S. adults believe marijuana has at least 1 risk, whereas 9% believe it has no risks. The most common risk identified by the public was legal problems (51.8%), followed by addiction (50%) and impaired memory (42%). Among U.S. adults, 29.2% agree that smoking marijuana prevents health problems. About 18% believe exposure to secondhand marijuana smoke is somewhat or completely safe for adults, whereas 7.6% indicated that it is somewhat or completely safe for children. Of the respondents, 7.3% agree that marijuana use is somewhat or completely safe during pregnancy. About 22.4% of U.S. adults believe that marijuana is not at all addictive. Limitation/UNASSIGNED:Wording of the questions may have affected interpretation. Conclusion/UNASSIGNED:Americans' view of marijuana use is more favorable than existing evidence supports. Primary Funding Source/UNASSIGNED:National Heart, Lung, and Blood Institute.

BACKGROUND:When shared by people who inject drugs, needles and syringes with different dead space may affect the probability of HIV and hepatitis C virus (HCV) transmission differently. METHODS:We measured dead space in 56 needle and syringe combinations obtained from needle and syringe programs across 17 countries in Europe and Asia. We also calculated the amounts of blood and HIV that would remain in different combinations following injection and rinsing. RESULTS:Syringe barrel capacities ranged from 0.5 to 20 mL. Needles ranged in length from 8 to 38 mm. The average dead space was 3 μL in low dead space syringes with permanently attached needles, 13 μL in high dead space syringes with low dead space needles, 45 μL in low dead space syringes with high dead space needles, and 99 μL in high dead space syringes with high dead space needles. Among low dead space designs, calculated volumes of blood and HIV viral burden were lowest for low dead space syringes with permanently attached needles and highest for low dead space syringes with high dead space needles. CONCLUSION:The dead space in different low dead space needle and syringe combinations varied substantially. To reduce HIV transmission related to syringe sharing, needle and syringe programs need to combine this knowledge with the needs of their clients.

New diagnoses of HIV-1 infection among people who inject drugs (PWID) rocketed in Athens, Greece between 2011 and 2014 (HIV-1 outbreak). Our aim was to identify, during that period, potential cross-group transmissions between the within-Greece PWID and other risk or national groups using molecular methods. Sequences from 33 PWID were outside the PWID-outbreak networks in Greece (PWID-imported transmissions). Phylogenetic analyses on 28 of these sequences (subtypes A and B) showed that 11 subtype B infections originated from Greece, whereas 8 and 7 subtype A strains were from former Soviet Union countries (A_FSU) and Greece, respectively. The putative source in half of the PWID-imported transmissions with Greek origin was an individual who acquired HIV via sexual contact. During four years of an HIV-1 outbreak among PWID in Athens, Greece, 33 individuals in this group (4.6% of all diagnoses with phylogenetic analyses) are likely to represent infections, sexually or injection-acquired, outside the within-Greece-PWID-outbreak networks. Combined molecular and traditional HIV surveillance to monitor introductions of new strains, and interventions that aim at reducing the rate of both injection and sexual risky practices are needed during drug injection-related HIV outbreaks.