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HIV-1 and HCV molecular epidemiology of a large
community outbreak of HIV-1 infection linked to
injection drug use of oxymorphone - Indiana, 2015
R.R. Galang, J. Gentry, P.J. Peters, S.J. Blosser, E.L. Chapman, C. Conrad, J.M. Duwve, L. Ganova-Raeva, W.
Heneine, D. Hillman, H. Jia, L. Liu, W. Luo, J. Lovchik, S. Masciotra, S.M. Owen, A. Perez, P. Peyrani, P. Pontones, S.
Ramachandran, J.C. Roseberry, M. Sandoval, A. Shankar, H. Thai, G. Xia, Y. Khudyakov, W.M. Switzer
Romeo R. Galang MD MPH
Epidemic Intelligence Service Officer
International AIDS Society Conference
Vancouver, Canada
July 20, 2015
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of HIV/AIDS Prevention
Disclosures

Neither I nor Dr. Galang have actual or potential conflicts of
interest in relation to this program/presentation.
Background
United States
State of Indiana:
Pop 6,596,850
Scott County:
Pop 24,181
Town of Austin:
Pop 4,200
Abstract A-729-0201-03716, J. Duwve et al. “Community outbreak of HIV infection linked to injection drug use of oxymorphone
– Indiana, 2015“
Poster WELBPE25, M. Spiller et al. “ Network analysis of a contact network from an investigation of a community outbreak of
HIV infection linked to injection drug use of oxymorphone – Indiana, 2015”
Public Health Importance

In an outbreak setting, determining the number, size, and recency
of infection clusters is important to guide the most effective
interventions

Laboratory support in this outbreak was used to:
• distinguish recent infections from prevalent infections
• suggest a common source between related infection strains

Traditionally these analyses are applied retrospectively once the
entire outbreak cohort has been defined

This investigation is one of few to use these techniques in realtime to inform decision making during the outbreak response
Objective

To infer the timing of HIV transmission relative to hepatitis C
virus (HCV) transmission

To infer the relatedness among HIV-positive isolates
Specimen Collection Methods

We analyzed serum and plasma samples from:
• Residents of Scott County and surrounding counties
• Positive antibody results for HIV and/or HCV
• Collected from October 2014 through April 2015
Photo: EISO Romeo Galang reviews specimen
collection with Disease Intervention Specialists
Figure: Source Counties for specimen collection
HIV-related Laboratory Methods

Recency of HIV-1 infection was determined by avidity testing
• Modified Bio-Rad HIV 1/2 plus O assay (BRAI)
• “Recent” infections are those that occurred within prior 6 months

Clustering was assessed by sequencing HIV-1 polymerase
(pol) gene sequences by polymerase chain reaction (PCR)

HIV-1 phylogenetic clusters were defined when:
1. HIV-1 pol sequences were highly genetically related
(>97% nucleotide identity)
2. Statistical evidence supporting relatedness was high
(Shimodaira-Hasegawa probabilities >0.99)
HCV-related Laboratory Methods

HCV NS5B and HVR1 gene sequences were amplified by PCR

HCV phylogenetic clusters were defined when:
• NS5B sequences belonged to the same genotype
• HVR1 sequences were highly genetically related
(>96.23% nucleotide identity)
Results
HIV-1 Recency Results (N=49)
100
90
Avidity Index (%)
80
70
60
50
40
Recent
Prevalent
30
20
10
0
Dec-7 Dec-27 Jan-16 Feb-5 Feb-25 Mar-17 Apr-6
Date of Specimen Collection
Note: Recency testing was performed using a Modified BioRad 1/2 Plus O
Assay with Avidity Index cutoff set at 30%
Maximum likelihood phylogenetic tree
of HIV-1 pol sequences (n=57)
1
0.98
0.83
1
0.9
0.77
0.95 0.76 0.95
1
0.88
0.89
0.94
0.84
0.95
0.79
0.83
0.93
0.790.75
0.77
0.9
1
0.85
0.89
0.97
0.84
0.85
0.99
Indiana outbreak samples*
References samples
1
1
1
0.97
0.93
0.92
0.98
0.96
1
0.93
0.83
0.86
0.92
0.86
0.91
1
0.87
0.93
0.97
0.9
0.780.84
0.85
0.98
0.83
0.77
0.89
0.79
0.7
0.78
1
1
0.97
1
0.02
* Tested as part of epidemiologic investigation
Maximum likelihood phylogenetic tree
of HCV NS5b sequences (n=119)
Indiana HCV Isolates
North America References
Cluster 1
1a
1b
2b
3a
Cluster 3
Example of non-clustering sequences
among reference sequences
Cluster 2
HCV Cluster distribution within HIV-1 pol phylogenetic tree (n=57)
0.98
1
0.83
1
0.9
0.77
0.95 0.76 0.95
1
0.88
0.89
0.94
0.84
0.95
0.79
0.83
0.93
0.790.75
0.77
0.9
1
Distribution of HCV Clusters within
HIV Cluster 1 (n = 55)
0.85
0.89
0.97
0.84
HCV Neg-Unk
28%
HCV Cluster 1
0.85
0.99
HCV Cluster 2
Cluster 1
55 patients
HCV
HCVNegative
Neg-Unk
35%
HCV Cluster 1
1
HCV no cluster
1
HCV Cluster 2
1
HCV No Cluster
0.97
0.93
0.92
0.98
0.96
0.02
0.83
0.86
0.92
0.86
0.91
1
0.87
0.93
0.97
0.9
0.780.84
0.85
0.98
0.83
0.77
0.89
0.79
0.7
0.78
1
0.97
1
1
1
0.93
15%
22%
Limitations

This analysis is limited to a subset of the outbreak cohort;
however, specimen collection and analysis are ongoing

Phylogenetic analysis only suggests a common source of
infection and cannot determine direction of transmission
Conclusions

A single strain of HIV-1 was recently introduced into a
population infected with multiple circulating HCV strains

Laboratory analyses can be conducted in real-time to meet
immediate decision making needs
Public Health Response

Tailored interventions were implemented in a geographically
concentrated area rather than broadly across the region

Retesting of contacts was performed given the large number
of recent HIV infections and on-going risk behavior
• Monitor pol sequences of new infections for spread of
outbreak strain

Future HIV infections are sequenced and compared with
representative outbreak sequences
Acknowledgements
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•
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Indiana State Department of Health (ISDH)
Scott County Health Department
Clark County Health Department
Foundations Family Medicine
Indiana University School of Medicine, Division of Infectious Diseases
University of Louisville School of Medicine, Division of Infectious Diseases
Division of HIV/AIDS Prevention (DHAP)
Division of Viral Hepatitis (DVH)
Epidemic Intelligence Service (EIS) Program Office
For more information please contact Centers for Disease Control and Prevention
1600 Clifton Road NE, Atlanta, GA 30333
Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348
Visit: www.cdc.gov | Contact CDC at: 1-800-CDC-INFO or www.cdc.gov/info
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the
Centers for Disease Control and Prevention.
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division Name in this space
Thank You!
For more information please contact Centers for Disease Control and Prevention
1600 Clifton Road NE, Atlanta, GA 30333
Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348
Visit: www.cdc.gov | Contact CDC at: 1-800-CDC-INFO or www.cdc.gov/info
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the
Centers for Disease Control and Prevention.
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division Name in this space