Shruti H. Mehta Gregory D. Kirk Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Ferbruary 22, 2017

1. The AIDS Linked to the
IntraVenous Experience (ALIVE)
Study
Shruti H. Mehta
Gregory D. Kirk
Department of Epidemiology
Johns Hopkins Bloomberg School of Public Health
February 22, 2016
http://www.jhsph.edu/research/affiliated-programs/AIDS-linked-to-the-intravenous-experience/

2. Proposal submitted to recruit
640 PWID and follow them for 5
years to identify factors
associated with AIDS
1986
1989
1994-1995
1998
2000
2005-2008
1987
1988
ALIVE I study funded
ALIVE II study funded
ALIVE Clinic opens and
recruits 2938 PWID in 13
months
434 new PWID recruited
244 new PWID recruited
51 women from the HERS
study enrolled in ALIVE
1004 new PWID recruited
History
B Frank Polk
1942-1988
David Vlahov
ALIVE I PI
Kenrad Nelson
ALIVE II PI
Steffanie Strathdee
ALIVE II PI
Greg Kirk
ALIVE I PI
Shruti Mehta
ALIVE II PI
2015-2017 450 (of 600 planned) new PWID
recruited; 5021 total enrollees

3. Overview of the ALIVE Study
 Location: Baltimore, MD
 Design: Community-based prospective cohort
 Enrollment: 1988-89, 1994-95, 1998, 2005-08, 2015-2016
 Recruitment: Community-based street outreach
 Follow-up visits: Semi-annual
 Total enrolled: 5,021
 Currently in follow-up: ~1100
 Inclusion criteria:
– >18 years of age
– Injection drug use in prior year
• Incidence: <1% per year
• Mortality: 2-3% per year
• Loss to follow-up: <5% per year

4. Core data collected at semi-annual visits
• Interviewer administered
– Alcohol / drug treatment
– Barriers to health care access
– Social support
• Nurse administered (REDCAP)
– Medical history
– Health care utilization
– HIV medicines, adherence
– Hepatitis C treatment history
• Audio computer-assisted self-interview
(ACASI)
– Drug use & risk behaviors
– Sexual risk behaviors
– Incarceration history
– Psychosocial, Quality of life
• Clinical Evaluation
– Physical exam (HIV+)
– Vitals, BMI
– FibroScan
– Functional status (SPPB)
– Spirometry
• Laboratory testing
– HIV antibody (HIV-)
– HIV viral load (HIV+)
– CD4 cell count (HIV+)
– CBC
– Lipid panel, Hgb-A1c, urine protein
– Serum chemistries, liver enzymes
– Periodic testing- HCV, HBV, HPV
– Repository (plasma, sera, cells, CVL,
DNA cell lines)
• Contextual
– Geocoded residential address
– Links to census data, data from Baltimore
Neighborhood Indicators Alliance
• Outcome Ascertainment
– Medical records
– NDI linkage
– Database linkages (Hopkins HIV Clinic,
MD Medicaid, USRDS, Cancer registry)
– CRISP (Chesapeake Regional
Information System for Patients)
All data collection instruments revised in 2015

5. Periodic surveys
• Food insecurity
• Health literacy
• Social network
survey added in
3/2016 (focused on HIV and
hepatitis C care support)
4. I would like you to think about the relations between the people you just mentioned. Some of them
may be total strangers in the sense that they wouldn’t recognize each other if they bumped into each
other on the street. Others may be especially close, as close to each other as they are to you.
4
A. First, think about [Name 1] and [Name 2]. Are _________ and ________ total strangers?
Yes
ASK 4.a FOR NEXT PAIR DOWN
No
ASK 4.B
B. On a scale of 1 to 5, how are close are [Name 1] and [Name 2]? One is not close at all
and 5 is very close.
SHOW CARD WITH CLOSENESS SCALE
ASK 4.a FOR NEXT PAIR DOWN
NAME 2 NAME 3 NAME 4 NAME 5
NAME 1 A. Yes 1 A. Yes 1 A. Yes 1 A. Yes 1
No 2 No 2 No 2 No 2
B. ___ B. ___ B. ___ B. ___
NAME 2 A. Yes 1 A. Yes 1 A. Yes 1
No 2 No 2 No 2
B. ___ B. ___ B. ___
NAME 3 A. Yes 1 A. Yes 1
No 2 No 2
B. ___ B. ___
NAME 4 A. Yes 1
No 2
B. ___
NAME 5
INTERVIEWER INSTRUCTION:
Refer to matrix on for question 4. Fill in unshaded boxes for each pair of network
members.

6. Characteristics of participants at
enrollment (n=5021)
1988-89 1994-95 1998 2005-08 2015-16
Median age 34 yrs 37 yrs 40 yrs 43 yrs 45 yrs
% male 82 67 65 64 77
% African American 88 95 95 66 58
% with at least high
school education
47 47 42 42 66
Median duration of
drug injection
13 yrs 15 yrs 18 yrs 19 yrs 18 yrs
% HIV positive 23 11 31 23 18
% Ever shared
needles
96 83 72 87 91
% Ever shooting
gallery
46 59 61 87 84

7. Characteristics of participants in
active follow-up (n=1101)
HIV negative HIV positive
Median age 55 yrs 55 yrs
% Male 67 67
% African-American 85 92
% Unemployed 87 90
% HCV antibody + 78 91
% Active alcohol use 48 47
% Non-injection drug
use
27 31
% Active drug injection 32 22

8. Major aims of the ALIVE Study
1. Natural history of drug abuse
2. Incidence of HIV, HCV and other blood-borne
infections
3. Impact of community-based interventions (e.g.,
NSEP, OAT, HCV test and treat initiatives)
4. Natural/treated history of HIV infection
5. Barriers to optimal engagement in HIV care
6. Natural/treated history of co-infections and
comorbidities
7. Serve as a platform for multidisciplinary research
ALIVEIIALIVEI

9. Major aims of the ALIVE Study
1. Natural history of drug abuse
2. Incidence of HIV, HCV and other blood-borne
infections
3. Impact of community-based interventions (e.g.,
NSEP, OAT, HCV test and treat initiatives)
4. Natural/treated history of HIV infection
5. Barriers to optimal engagement in HIV care
6. Natural/treated history of co-infections and
comorbidities
7. Serve as a platform for multidisciplinary
ALIVEIIALIVEI

10. Trajectories of drug injection over 20 years
Early cessation
(19%)
Delayed cessation
(16%)
Late cessation
(18%)
Frequent relapse
(16%)
Persistent injection
(32%)
Genberg BL et al Am J Epidemiol 2011

11. Impact of residential rehabilitation on injection
drug use patterns
Linton S et al Health Place 2014; Linton S et al J Urb Health 2014

12. Changing trends in drug use
(Newer initiates start with prescription drugs)
0
10
20
30
40
50
60
70
80
90
100
1950/1960s 1970s 1980s 1990/2000s Current
Time period
Pills Non-injection Injection
First drug used
Cepeda J et al Submitted

13. Major aims of the ALIVE Study
1. Natural history of drug abuse
2. Incidence of HIV, HCV and other blood-borne
infections
3. Impact of community-based interventions (e.g.,
NSEP, OAT, HCV test and treat initiatives)
4. Natural/treated history of HIV infection
5. Barriers to optimal engagement in HIV care
6. Natural/treated history of co-infections and
comorbidities
7. Serve as a platform for multidisciplinary
ALIVEIIALIVEI

14. Development of multi-assay algorithms for
measuring cross-sectional HIV incidence
Cousins MM, Konikoff J, Sabin D, Khaki L, Longosz AF, et al. (2014) A Comparison of Two Measures of HIV Diversity in Multi-Assay
Algorithms for HIV Incidence Estimation. PLoS ONE 9(6): e101043. doi:10.1371/journal.pone.0101043
http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0101043

15. Major aims of the ALIVE Study
1. Natural history of drug abuse
2. Incidence of HIV, HCV and other blood-borne
infections
3. Impact of community-based interventions (e.g.,
NSEP, OAT, HCV test and treat initiatives)
4. Natural/treated history of HIV infection
5. Barriers to optimal engagement in HIV care
6. Natural/treated history of co-infections and
comorbidities
7. Serve as a platform for multidisciplinary
ALIVEIIALIVEI

16. A transmission model to determine potential impact of
HCV treatment as prevention among PWID
Mier-y-Teran Romerp L et al CROI 2016

17. Major aims of the ALIVE Study
1. Natural history of drug abuse
2. Incidence of HIV, HCV and other blood-borne
infections
3. Impact of community-based interventions (e.g.,
NSEP, OAT, HCV test and treat initiatives)
4. Natural/treated history of HIV infection
5. Barriers to optimal engagement in HIV care
6. Natural/treated history of co-infections and
comorbidities
7. Serve as a platform for multidisciplinary research
ALIVEIIALIVEI

18. Westergaard R et al, AIDS, 2013
Improved survival but ART uptake &
utilization is still not optimal

19. Major aims of the ALIVE Study
1. Natural history of drug abuse
2. Incidence of HIV, HCV and other blood-borne
infections
3. Impact of community-based interventions (e.g.,
NSEP, OAT, HCV test and treat initiatives)
4. Natural/treated history of HIV infection
5. Barriers to optimal engagement in HIV care
6. Natural/treated history of co-infections and
comorbidities
7. Serve as a platform for multidisciplinary research
ALIVEIIALIVEI

20. NCD and geriatric phenotypes evaluated in
ALIVE
• Liver fibrosis, ESLD
• Lung disease (COPD,
PAH)
• Hypertension, cardiac
fibrosis
• Diabetes, obesity, BMI
• CKD, proteinuria, ESRD
• Cancer
• Neurocognitive function
• Bone disease, falls
• Multimorbidity
• Frailty
• Physical performance
• Gait speed, grip
strength, balance,
SPPB

21. Frailty predicts mortality independent of HIV
Piggott DA et al. PLoS One 2013
7 Fold More Likely to Die
If you have HIV and are
FRAIL

22. Major aims of the ALIVE Study
1. Natural history of drug abuse
2. Incidence of HIV, HCV and other blood-borne
infections
3. Impact of community-based interventions (e.g.,
NSEP, OAT, HCV test and treat initiatives)
4. Natural/treated history of HIV infection
5. Barriers to optimal engagement in HIV care
6. Natural/treated history of co-infections and
comorbidities
7. Serve as a platform for multidisciplinary
ALIVEIIALIVEI

23. Multidisciplinary Scope of the ALIVE Study
• Research ranges from behavioral, clinical, epidemiologic
and laboratory / translational
• >30 ALIVE faculty investigators with broad expertise
• Repository with 1.2 million unique aliquots of sera, plasma
PBMCs and other biospecimens
• Supports research by students, fellows, and junior faculty
• >400 peer-reviewed publications
• In last funding period, >25 R01 or similar NIH grants and 6
K-awards
• Avenir, Fulbright and Amos Award winners in last year

24. How can I initiate a collaboration?
• Email Principal Investigators
– Shruti Mehta smehta@jhu.edu
– Greg Kirk gdk@jhu.edu
• Collaboration can be
– Data request
– Data analysis
– Repository request

25. Acknowledgements
• Study participants
• Study and admin support staff
• NIDA funding
• Many, many collaborators