Health Outcomes by Neighborhood - Baltimore

PHASE C - ENROLLMENT BEGIN MARCH 2017

Background: Increasing HIV testing and entry into prevention services remains an important
public health goal, in addition to reducing disparities in the incidence of HIV and treatment
outcomes. In this study, we will examine environmental influences on HIV risk/transmission
and treatment and prevention. The data we collect will inform our plans to use our section s
geographical and predictive analytics in a new way, predicting where HIV prevention efforts
should be targeted on a time scale of weeks or months. This is a question of interest to the
Baltimore City Health Department, among others, and the 472 protocol provides the most
efficient and logical way for us to begin collecting the relevant data.

Scientific goals: (1) To determine how activity space, as assessed with geographical
momentary assessment (GMA), influences HIV status, knowledge of HIV-related healthcare and
likelihood of seeking care, and risk/transmission behavior. (2) To determine differences in
activity spaces between HIV-positive people and HIV-negative people in their social networks.
(3) To assess the effects of mental health and cognition (executive function, impulsivity) on
differences in activity spaces between HIV-positive and HIV-negative people. (4) To explore
the role of phylogenetics and its interplay with environment in regards to drug use
initiation, HIV risk as it relates to drug use, drug injection, and needle sharing. (5) to
assess EMA reports of drug use and psychosocial stress as well as real-time environmental
risk exposure among individuals with and without HIV.

Participant population: We will enroll HIV-positive adults (at least 75 enrolled; at least 60
completers) and HIV-negative adults (up to 225 enrolled; up to 180 completers) within their
social networks for a total enrollment of 300 participants. Target enrollment will include
25% women and 70% minorities (mostly African-American).

Experimental design and methods: This is a two-group observational study. Each participant
will be assessed in one main study visit and 5 additional visits for the EMA/GMA component of
the study. The two main groups will be: (1) HIV+ participants, and (2) HIV- participants who
are within the social network of HIV+ participants. Each group will be roughly matched for
socioeconomic status and neighborhoods of residence. Each participant will attend a 3-5-hour
initial study visit, a 1-hour training session for the EMA/GMA component, and four weekly
30-minute EMA/GMA compliance visits. The study visit will include a questionnaire component
and a biological-sample component. Questionnaires will cover substance use, stress, social
stability (including healthcare access/utilization, and neighborhood environment), physical
and mental health (including quality of life, HIV, and mood). The biological component will
consist of samples of urine (for drugs of abuse and cotinine), and breath (for alcohol and
carbon monoxide). Blood for genetics will also be obtained at Visit 1. The primary outcome
measures will be activity spaces as assessed with EMA and GMA, HIV status, knowledge of
HIV-related healthcare and likelihood of seeking care, as well as risk/transmission behavior.
Secondary outcome measures will include: biological assessments of drug use; medical,
psychiatric, social determinants of health; impulsivity and decision-making tendencies.
Participants will carry a smartphone for up to 4 weeks after completing Visit 1.
Event-triggered entries will be initiated by participants (1) each time that they use a drug
and/or alcohol, and (2) each time they engage in sexual activities with a partner.
Participants will also make 5 random-signal-triggered recordings per day and one brief end of
day recording.

Benefits to participants and/or society: There are no benefits to participants. The knowledge
gained may benefit society by providing data on the health outcomes of HIV -positive and
HIV-negative individuals by neighborhood.

Risks to participants: This is a minimal-risk study, consisting of standard physical and
questionnaire-based assessments.

PHASE B - ENROLLMENT BEGIN JANUARY 2016

Background: The reasons for initiation and continuation of use of illicit substances are
multifactorial; however, some individuals appear resistant to both. One set of determinants
lies in the environment. In ongoing studies, we are examining environmental concomitants of
behavior in individuals in drug treatment. In this study, we will examine environmental
factors that may impact initiation, addiction, and treatment seeking among the greater
population at large (non-drug-users, current opioid/stimulant users, and current marijuana
users).

Scientific goals: (1) To assess, cross-sectionally at baseline, differences in stress, social
stability, and mental and physical health among three main neighborhood-matched groups of
current opioid/stimulant users, current marijuana users, and nondrug users; (2) to assess,
longitudinally, mediators of 12-month changes in drug-misuse status in the same three groups;
(3) to provide neighborhood-matched control groups of non-drug-using individuals,
Unclassified/former drug users, and current opioid/stimulant drug users not seeking treatment
for our ongoing environmental studies of individuals in drug treatment; (4) to explore the
possible role of genetics and its interplay with environment in regards to drug use
initiation, addiction, and treatment seeking among the study groups, and (5) to assess EMA
reports of drug use and psychosocial stress as well as real-time environmental risk exposure
in a non-treatment seeking and/or nondrug using population and compare to our ongoing
environmental studies of individuals in drug treatment,

Participant population: We will enroll 500 participants in Phase B of the study for a total
enrollment (Phase A + Phase B) of 1250 participants. Target enrollment will include 25% women
and 70% minorities (mostly African-American).

Experimental design and methods: This is a three-group observational study with a
cross-sectional component and a longitudinal component: each participant will be assessed in
two visits spaced approximately 12 months apart. The three main groups will be: (1)
non-drug-users (NDUs), (2) current opioid/stimulant users [(COSUs) comprised of two
subgroups: treatment seeking (COSU-TS) and non-treatment seeking (COSU-NTS)], and current
marijuana users (CMUs). All groups will be roughly matched for socioeconomic status and
neighborhoods of residence. Each participant will attend a 3-5-hour initial study visit and a
3-5-hour 12 month visit #2. The study visits will include a questionnaire component and a
biological-sample component. Questionnaires will cover substance use, stress, social
stability (including healthcare access/utilization, and neighborhood environment), physical
and mental health (including quality of life, HIV, and trauma). The biological component will
consist of samples of urine (for drugs of abuse and cotinine), breath (for alcohol and carbon
monoxide). Blood for genetics will be obtained at Visit 1 or Visit 2. The primary outcome
measures will be lifetime substance-misuse history (cross-sectional component) and changes in
drug-use status across the 12 months between visits (longitudinal component). Secondary
outcome measures will include: biological assessments of drug use; medical, psychiatric,
social determinants of health; and impulsivity and decision-making factors. Individuals who
choose not to return for a 12-month Visit #2 will be asked to complete a 45-minute telephone
visit #2. In the HON EMA/GMA secondary study participants will carry a smartphone and a GPS
unit (if necessary) for up to 4 weeks after completing Visit 1. Event-triggered entries will
be initiated by participants (1) each time that they use a drug (COSU) or marijuana and/or
alcohol (NDU, CMU, and Unclassified) and (2) each time they feel overwhelmed, anxious, or
stressed more than usual. Participants will also make 5 random-signal-triggered recordings
per day and one brief end of day recording. During this study participants will also come to
the clinic once a week to complete compliance visits.

Benefits to participants and/or society: There are no benefits to participants. The knowledge
gained may benefit society by providing data on the health outcomes of drug-using and
non-drug-using individuals and the natural history of drug use by neighborhood.

Risks to participants: This is a minimal-risk study, consisting of standard physical and
questionnaire-based assessments.

PHASE A - ENROLLMENT ENDED DECEMBER 2015

Background. The reasons for initiation and continuation of use of illicit substances are
multifactorial; however, some individuals appear resistant to both. One set of determinants
lies in the environment. In ongoing studies, we are examining environmental concomitants of
behavior in individuals in drug treatment. In this study, we will examine environmental
factors that may impact initiation, addiction, and treatment seeking among the greater
population at large (non-drug-users, former drug users, current opioid/stimulant users
seeking treatment, current opioid/stimulant users not seeking treatment, and current
marijuana users). Using the same participants, we will also investigate lipid biomarkers as
predictors of relapse; this portion of the study will be a collaboration with preclinical
investigators who have identified a possible lipid fingerprint of cocaine sensitization. The
results could inform prevention efforts, enhance treatment interventions, and improve
substance use outcomes.

Scientific goals: (1) To assess, cross-sectionally at baseline, differences in stress, social
stability, and mental and physical health among three neighborhood-matched groups of current
opioid/stimulant users, current marijuana users, and nondrug users; (2) to assess,
longitudinally, mediators of 12-month changes in drug-misuse status in the same three groups;
(3) to provide neighborhood-matched control groups of non-drug-using individuals, former drug
users, and current drug users not seeking treatment for our ongoing environmental studies of
individuals in drug treatment; (4) to assess lipid biomarkers as predictors of drug relapse
with the eventual goal of developing a screening assay that will inform the personalization
of treatment, (5) to explore the possible role of genetics and its interplay with environment
in regards to drug use initiation, addiction, and treatment seeking among the study groups,
and (6) to test blood serum and urine for the presence of several disease-associated
autoantibodies, including ANCA, ANA, and antiophospholipid antibodies, in relation to the
presence of levamisole (a common adulterant in cocaine); (7) to assess EMA reports of drug
use and psychosocial stress as well as real-time environmental risk exposure in a
non-treatment seeking and/or nondrug using population and compare to our ongoing
environmental studies of individuals in drug treatment,

Participant population: We will enroll up to 750 community-dwelling individuals (at least 300
of whom we anticipate will provide 12-month Visit #2 data for our 3 main study groups).
Target enrollment will include 25% women and 70% minorities (mostly African-American).

Experimental design and methods: This is a three-group observational study with a
cross-sectional component and a longitudinal component: each participant will be assessed in
two visits spaced approximately 12 months apart. The three groups will be: (1) non-drug-users
(NDUs), (2) current opioid/stimulant users (COSUs), and current marijuana users (CMUs). All
groups will be roughly matched for socioeconomic status and neighborhoods of residence. Each
participant will attend a 5-hour initial study visit and a 5-hour 12 month visit #2. The
study visits will include a questionnaire component and a biological-sample component.
Questionnaires will cover substance use, stress, social stability (including healthcare
access and utilization), physical and mental health (including quality of life, dental
health, pain, sexual function, sleep, HIV, trauma). The biological component will consist of
samples of urine (for drugs of abuse, cotinine, microalbumin), breath (for alcohol and carbon
monoxide), saliva (for alpha-amylase and cortisol), and blood (for liver function, kidney
function, HGBA1C, DHEA-S, lipids, CRP, pre-albumin, cortisol, and lipid biomarkers). Blood
for genetics will be obtained at Visit 1 or Visit 2. Blood and urine for the levamisole
secondary study will be collected at Visit 1 and/or Visit 2. The primary outcome measures
will be lifetime substance-misuse history (cross-sectional component) and changes in drug-use
status across the 12 months between visits (longitudinal component). Secondary outcome
measures will include: biological assessments of drug use; lipid biomarkers; medical,
psychiatric, and social determinants of health; hematologic markers corresponding to medical
conditions; measure of cumulative stress burden (allostatic load); personality assessment;
and the relationships among levels of autoantibodies, levamisole, and cocaine metabolites.
Individuals who choose not return for a 12-month Visit #2 will be asked to complete a
45-minute telephone visit #2. Individuals in Group 1 (NDU) will also be offered an optional
8-hour laboratory stress session (472 Stress Exposure and Response Session A: 472 SEARSA).
The 472 SEARSA session will occur on a separate day, under a separate consent, and will
consist of color-vision testing and the Paced Auditory Serial Addition Task (PASAT-C), a
psychological stressor. The 472 SEARSA session replicates the 09-DA-N020 Stress Exposure and
Response Session A, which is conducted with methadone-maintained opioid-dependent
participants, and will thereby provide a non-drug-using neighborhood-matched control group
for comparison of stressor reactivity and color vision. In the HON EMA/GMA secondary study
participants will carry a smartphone and a GPS unit (if necessary) for up to 4 weeks after
completing Visit 1. Event-triggered entries will be initiated by participants (1) each time
that they use a drug and (2) each time they feel overwhelmed, anxious, or stressed more than
usual. Participants will also make 5 random-signal-triggered recordings per day and one brief
end of day recording. During this study participants will also come to the clinic once a week
to provide urine and breath samples, complete questionnaires, and upload data from their
devices.

Benefits to participants and/or society: There are no benefits to participants. The knowledge
gained may benefit society by providing data on the health outcomes of drug-using and
non-drug-using individuals and the natural history of drug use by neighborhood.

Risks to participants: This is a minimal-risk study, consisting of standard physical and
questionnaire-based assessments. Participants who undergo the PASAT-C are expected to
experience only mild, transient stress.

- INCLUSION CRITERIA:

- Age at least 18 years. Rationale: Children under 18 will not be included because many
of the measures to be administered in this study are not validated for use with
children. Furthermore, the research question under investigation is the drug
trajectories of adults, over the age of 18. However, there is no intervention in this
study that is contraindicated for older adults, and given that addiction in the
elderly is understudied, it is important to include elderly individuals.

- Residence in Baltimore city or one of the surrounding counties. Rationale: Our current
geographic mapping technology currently only includes these areas.

EXCLUSION CRITERIA:

-Inability to provide informed consent.