Detailed Transmission Network Analysis of a Large Opiate-Driven Outbreak of HIV Infection in the United States

In January 2015, an outbreak of undiagnosed human immunodeficiency virus (HIV) infections among persons who inject drugs (PWID) was recognized in rural Indiana. By September 2016, 205 persons in this community of approximately 4400 had received a diagnosis of HIV infection. We report results of new approaches to analyzing epidemiologic and laboratory data to understand transmission during this outbreak. HIV genetic distances were calculated using the polymerase region. Networks were generated using data about reported high-risk contacts, viral genetic similarity, and their most parsimonious combinations. Sample collection dates and recency assay results were used to infer dates of infection. Epidemiologic and laboratory data each generated large and dense networks. Integration of these data revealed subgroups with epidemiologic and genetic commonalities, one of which appeared to contain the earliest infections. Predicted infection dates suggest that transmission began in 2011, underwent explosive growth in mid-2014, and slowed after the declaration of a public health emergency. Results from this phylodynamic analysis suggest that the majority of infections had likely already occurred when the investigation began and that early transmission may have been associated with sexual activity and injection drug use. Early and sustained efforts are needed to detect infections and prevent or interrupt rapid transmission within networks of uninfected PWID.

[1]  T. Wong,et al.  Sexual network analysis of a gonorrhoea outbreak , 2004, Sexually Transmitted Infections.

[2]  T. McFarlane.  EMERGENCE OF ACUTE HEPATITIS C IN YOUNG INDIANA RESIDENTS WHO INJECT DRUGS , 2013 .

[3]  J. Strathern,et al.  Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. , 2005, The Journal of infectious diseases.

[4]  A. Rambaut,et al.  Episodic Sexual Transmission of HIV Revealed by Molecular Phylodynamics , 2008, PLoS medicine.

[5]  C. Beyrer,et al.  Threading the Needle--How to Stop the HIV Outbreak in Rural Indiana. , 2015, The New England journal of medicine.

[6]  A. Vandamme,et al.  HIV forensics: pitfalls and acceptable standards in the use of phylogenetic analysis as evidence in criminal investigations of HIV transmission * , 2007, HIV medicine.

[7]  Edward C. Holmes,et al.  Discovering the Phylodynamics of RNA Viruses , 2009, PLoS Comput. Biol..

[8]  B. Lewis,et al.  Transmission network analysis in tuberculosis contact investigations. , 2007, The Journal of infectious diseases.

[9]  Philip J. Peters,et al.  Community Outbreak of HIV Infection Linked to Injection Drug Use of Oxymorphone — Indiana, 2015 , 2015, MMWR. Morbidity and mortality weekly report.

[10]  O. WertheimJoel,et al.  The International Dimension of the U.S. HIV Transmission Network and Onward Transmission of HIV Recently Imported into the United States , 2016 .

[11]  Angela L Hernandez,et al.  Mean Recency Period for Estimation of HIV-1 Incidence with the BED-Capture EIA and Bio-Rad Avidity in Persons Diagnosed in the United States with Subtype B , 2016, PloS one.

[12]  D. Holtzman,et al.  Syringe Service Programs for Persons Who Inject Drugs in Urban, Suburban, and Rural Areas - United States, 2013. , 2015, MMWR. Morbidity and mortality weekly report.

[13]  O. Pybus,et al.  Unifying the Epidemiological and Evolutionary Dynamics of Pathogens , 2004, Science.

[14]  P. Heagerty,et al.  Readiness of high‐risk populations in the HIV Network for Prevention Trials to participate in HIV vaccine efficacy trials in the United States , 1998, AIDS.

[15]  U. Bauer,et al.  [Centers for Disease Control and Prevention (CDC)]. , 2000, Annales de dermatologie et de venereologie.

[16]  Ann M. Dennis,et al.  Characterizing HIV transmission networks across the United States. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  Joel O. Wertheim,et al.  Using HIV Networks to Inform Real Time Prevention Interventions , 2014, PloS one.

[18]  Ingo Bulla,et al.  Phylogenetically resolving epidemiologic linkage , 2016, Proceedings of the National Academy of Sciences.

[19]  P. Mcelroy,et al.  Transmission network analysis to complement routine tuberculosis contact investigations. , 2007, American journal of public health.

[20]  G. Stiles,et al.  Development and impact of prescription opioid abuse deterrent formulation technologies. , 2014, Drug and alcohol dependence.

[21]  C. Fraser,et al.  A New Framework and Software to Estimate Time-Varying Reproduction Numbers During Epidemics , 2013, American journal of epidemiology.

[22]  Joel O. Wertheim,et al.  Using HIV Transmission Networks to Investigate Community Effects in HIV Prevention Trials , 2011, PloS one.

[23]  J. O. Wertheim,et al.  Molecular analysis allows inference into HIV transmission among young men who have sex with men in the United States , 2015, AIDS.

[24]  Christopher M. Jones,et al.  County-Level Vulnerability Assessment for Rapid Dissemination of HIV or HCV Infections Among Persons Who Inject Drugs, United States , 2016, Journal of acquired immune deficiency syndromes.

[25]  P. Harrigan,et al.  The impact of clinical, demographic and risk factors on rates of HIV transmission: a population-based phylogenetic analysis in British Columbia, Canada. , 2015, The Journal of infectious diseases.

[26]  D. Pillay,et al.  Understanding Drivers of Phylogenetic Clustering in Molecular Epidemiological Studies of HIV , 2014, The Journal of infectious diseases.

[27]  T. Walker,et al.  Contact investigations for outbreaks of Mycobacterium tuberculosis: advances through whole genome sequencing. , 2013, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[28]  J. O. Wertheim,et al.  Using Molecular HIV Surveillance Data to Understand Transmission Between Subpopulations in the United States , 2015, Journal of acquired immune deficiency syndromes.

[29]  T. Cicero,et al.  A tale of 2 ADFs: differences in the effectiveness of abuse-deterrent formulations of oxymorphone and oxycodone extended-release drugs , 2016, Pain.

[30]  Sergei L. Kosakovsky Pond,et al.  The global transmission network of HIV-1. , 2014, The Journal of infectious diseases.

[31]  Michael W. Spiller,et al.  HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014-2015. , 2016, The New England journal of medicine.

[32]  A. Oster,et al.  Sexually transmitted infection diagnoses among Hispanic immigrant and migrant men who have sex with men in the United States , 2016, International journal of STD & AIDS.

[33]  M. Everett,et al.  Recent network evolution increases the potential for large epidemics in the British cattle population , 2007, Journal of The Royal Society Interface.

[34]  D. Pieniążek,et al.  Demographic but not geographic insularity in HIV transmission among young black MSM , 2011, AIDS.

[35]  A. Hatzakis,et al.  Economic Recession and Emergence of an HIV-1 Outbreak among Drug Injectors in Athens Metropolitan Area: A Longitudinal Study , 2013, PloS one.

[36]  R. May,et al.  Infectious disease dynamics: What characterizes a successful invader? , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.