Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter November 11, 2020

Challenges in evaluating the use of viral sequence data to identify HIV transmission networks for public health

Rami Kantor, John P. Fulton, Jon Steingrimsson, Vladimir Novitsky, Mark Howison, Fizza Gillani, Yuanning Li, Akarsh Manne, Zoanne Parillo, Matthew Spence, Theodore Marak, Philip Chan, Casey W. Dunn, Thomas Bertrand, Utpala Bandy, Nicole Alexander-Scott and Joseph W. Hogan


Great efforts are devoted to end the HIV epidemic as it continues to have profound public health consequences in the United States and throughout the world, and new interventions and strategies are continuously needed. The use of HIV sequence data to infer transmission networks holds much promise to direct public heath interventions where they are most needed. As these new methods are being implemented, evaluating their benefits is essential. In this paper, we recognize challenges associated with such evaluation, and make the case that overcoming these challenges is key to the use of HIV sequence data in routine public health actions to disrupt HIV transmission networks.

Corresponding author: John P. Fulton, Brown University, Providence, RI, USA, E-mail:

Funding source: National Institute of Allergy and Infectious Diseases

Award Identifier / Grant number: R01 AI136058, P30 AI042853

  1. Research funding: This research was funded by the National Institute of Allergy and Infectious Diseases (R01 AI136058, P30 AI042853).

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.


Antiretroviral Therapy Cohort Collaboration. 2008. “Life Expectancy of Individuals on Combination Antiretroviral Therapy in High-income Countries: A Collaborative Analysis of 14 Cohort Studies.” Lancet 372: 293–9.10.1016/S0140-6736(08)61113-7Search in Google Scholar

Armbruster, B., and M. L. Brandeau. 2007. “Contact Tracing to Control Infectious Disease: When Enough Is Enough.” Health Care Management Science 10 (4): 341–55, PMID: 18074967; PMCID: PMC3428220.Search in Google Scholar

Brenner, B. G., M. Roger, D. Stephens, D. Moisi, I. Hardy, J. Weinberg, R. Turgel, H. Charest, J. Koopman, and M. A. Wainberg. 2011. “Transmission Clustering Drives the Onward Spread of the HIV Epidemic Among Men Who Have Sex with Men in Quebec.” The Journal of Infectious Diseases 204 (7): 1115–19, in Google Scholar

Centers for Disease Control and Prevention. 2008. “Recommendations for Partner Services Programs for HIV Infection, Syphilis, Gonorrhea, and Chlamydial Infection.” Morbidity and Mortality Weekly Report Recommendations and Reports 57 (No. RR-9). in Google Scholar

Centers for Disease Control and Prevention. 2019a. Advancing HIV Prevention through Cluster Detection and Response. Also available at in Google Scholar

Centers for Disease Control and Prevention. 2019b. Ending the HIV Epidemic – HIV Treatment Is Prevention. Vital Signs. Also available at in Google Scholar

Centers for Disease Control and Prevention. 2019c. HIV Cluster and Outbreak Detection and Response. Also available at in Google Scholar

Chan, P. A., J. W. Hogan, A. Huang, A. DeLong, M. Salemi, K. H Mayer, and R. Kantor. 2015. “Phylogenetic Investigation of a Statewide HIV-1 Epidemic Reveals Ongoing and Active Transmission Networks Among Men Who Have Sex with Men.” Journal of Acquired Immune Deficiency Syndromes 70 (4): 428–35, in Google Scholar

Cohen, M. S., Y. Q. Chen, M. McCauley, T. Gamble, M. C. Hosseinipour, N. Kumarasamy, J. G. Hakim, J. Kumwenda, B. Grinsztejn, J. H. S. Pilotto, S. V. Godbole, S. Mehendale, S. Chariyalertsak, B. R. Santos, K. H. Mayer, I. F. Hoffman, S. H. Eshleman, E. Piwowar-Manning, L. Wang, J. Makhema, L. A. Mills, G. de Bruyn, I. Sanne, J. Eron, J. Gallant, D. Havlir, S. Swindells, H. Ribaudo, V. Elharrar, D. Burns, T. E. Taha, K. Nielsen-Saines, D. Celentano, M. Essex, and T. R. Fleming. 2011. “Prevention of HIV-1 Infection with Early Antiretroviral Therapy.” New England Journal of Medicine 365 (6): 493–505. PMID: 21767103, in Google Scholar

DHHS. 2015. Panel on Antiretroviral Guidelines for Adults and Adolescents, 133–39. Washington (DC). Also Available at in Google Scholar

Eisinger, R. W., C. W. Dieffenbach, and A. S. Fauci. 2019. “HIV Viral Load and Transmissibility of HIV Infection: Undetectable Equals Untransmittable.” Journal of the American Medical Association 321 (5): 451–2, No abstract available. PMID: 30629090.Search in Google Scholar

Grabowski, M. K., and A. D. Redd. 2014. “Molecular Tools for Studying HIV Transmission in Sexual Networks.” Current Opinion in HIV and AIDS 9 (2): 126–33, PMID: 24384502.Search in Google Scholar

Green, N., M. Hoenigl, A. Chaillon, C. M. Anderson, S. L. Kosakovsky Pond, D. M. Smith, and S. J. Little. 2017. “Partner Services in Adults with Acute and Early HIV Infection.” AIDS 31 (2): 287–93, in Google Scholar

Gueler, A., A. Moser, A. Calmy, H. F. Günthard, E. Bernasconi, H. Furrer, C. A. Fux, M. Battegay, M. Cavassini, P. Vernazza, M. Zwahlen, and M. Egger. 2017. “Life Expectancy in HIV-positive Persons in Switzerland: Matched Comparison with General Population.” AIDS 31: 427–36, in Google Scholar

Jones, J., P. S. Sullivan, and J. W. Curran. 2019. “Progress in the HIV Epidemic: Identifying Goals and Measuring Success.” PLoS Medicine 16 (1): e1002729, eCollection 2019 Jan. PMID: 30657770.Search in Google Scholar

Joint United Nations Programme on HIV/AIDS. 2019. Communities at the Centre: Global AIDS Update 2019. 6–7. Geneva: UNAIDS. Also available at in Google Scholar

Kosakovsky Pond, S. L., S. Weaver, A. J. Leigh Brown, and J. O. Wertheim. 2018. “HIV-TRACE (TRAnsmission Cluster Engine): A Tool for Large Scale Molecular Epidemiology of HIV-1 and Other Rapidly Evolving Pathogens.” Molecular Biology and Evolution 35 (7): 1812–19, PMID: 29401317.Search in Google Scholar

Little, S. J., S. L. Kosakovsky Pond, C. M. Anderson, J. A. Young, J. O. Wertheim, S. R. Mehta, S. May, and D. M. Smith. 2014. “Using HIV Networks to Inform Real Time Prevention Interventions.” PLoS One 9 (6): e98443, in Google Scholar

Maddison, W. P. 1997. “Gene Trees in Species Trees.” Systematic Biology 46 (3): 523–36, in Google Scholar

Magaziner, S., M. C. Montgomery, T. Bertrand, D. Daltry, H. Jenkins, B. Kendall, L. Molotnikov, L. Pierce, E. Smith, L. Sosa, J. J. van den Berg, T. Marak, D. Operario, and P. A. Chan. 2018. “Public Health Opportunities and Challenges in the Provision of Partner Notification Services: The New England Experience.” BMC Health Services Research 18 (1): 75, PMID: 29386023.Search in Google Scholar

Mehta, S. R., C. Schairer, and S. Little. 2019. “Ethical Issues in HIV Phylogenetics and Molecular Epidemiology.” Current Opinion in HIV and AIDS 14 (3): 221–6, PMID: 30946143.Search in Google Scholar

Novitsky, V., M. Howison, F. Gillani, M. Akarsh, J. Hogan, J. Steingrimsson, C. Dunn, Y. Li, N. Alexander-Scott, U. Bandy, P. Chan, T. Bertrand, T. Marak, M. Spencer, J. Fulton, and R. Kantor. 2019. HIV-1 Subtype B Transmission Clusters Identified by Phylogenetic and Network Analysis. In HIV Dynamics and Evolution Conference, March 24–27, 2019, Cascais, Portugal. PMID: 33122765.Search in Google Scholar

Peters, P. J., P. Pontones, K. W. Hoover, M. R. Patel, R. R. Galang, J. Shields, S. J. Blosser, M. W. Spiller, B. Combs, W. M. Switzer, C. Conrad, J. Gentry, Y. Khudyakov, D. Waterhouse, S. Michele Owen, E. Chapman, J. C. Roseberry, V. McCants, P. J. Weidle, D. Broz, T. Samandari, J. Mermin, J. Walthall, J. T. Brooks, J. M. Duwve. 2016. “HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014-2015.” New England Journal of Medicine 375 (3): 229–39, in Google Scholar

Poon, A. F., R. Gustafson, P. Daly, L. Zerr, S. E. Demlow, J. Wong, C. K. Woods, R. S. Hogg, M. Krajden, D. Moore, P. Kendall, J. S. G. Montaner, and P. Richard Harrigan. 2016. “Near Real-time Monitoring of HIV Transmission Hotspots from Routine HIV Genotyping: An Implementation Case Study.” Lancet HIV 3 (5): e231–238, in Google Scholar

Som, A. 2015. Causes, Consequences and Solutions of Phylogenetic Incongruence. Briefings in Bioinformatics 16 (3): 536–48, in Google Scholar

Tributino, A., M. C. Montgomery, T. Bertrand, T. Marak, A. Almonte, J. van den Berg, K. St John, C. Browning, M. M. Medina, A. Morse, and P. A. Chan. 2018. “Partner Notification Outcomes after Integration of an On-site Disease Intervention Specialist at a Sexually Transmitted Disease Clinic.” PLoS One 13 (3): e0194041, eCollection 2018. PMID: 29584743.Search in Google Scholar

United Nations General Assembly. 2016. Political Declaration on HIV and AIDS: On the Fast-Track to Accelerate the Fight against HIV and to End the AIDS Epidemic by 2030.Search in Google Scholar

United States Health Resources and Services Administration (HRSA). Ending the HIV Epidemic: Initiative Goals. Also available at in Google Scholar

United States Health Resources and Services Administration (HRSA). Ending the HIV Epidemic: A Plan for America. Also available at in Google Scholar

Wertheim, J. O., C. Chato, and A. F. Y. Poon. 2019. “Comparative Analysis of HIV Sequences in Real Time for Public Health.” Current Opinion in HIV and AIDS 14 (3): 213–20, PMID: 30882486.Search in Google Scholar

WHO. 2018. Global Health Observatory (GHO) Data. [HIV/AIDS]. Also available at in Google Scholar

Workowski, K. A., and G. A. Bolan. 2015. “Sexually Transmitted Diseases Treatment Guidelines, 2015.” Morbidity and Mortality Weekly Report Recommendations and Reports 64 (No. RR-3): 24. in Google Scholar

Received: 2019-11-01
Accepted: 2020-10-22
Published Online: 2020-11-11

© 2020 Walter de Gruyter GmbH, Berlin/Boston