Social and Genetic Networks of HIV-1 Transmission in New York City

Abstract

Background: Sexually transmitted infections spread across contact networks. Partner elicitation and notification are commonly used public health tools to identify, notify, and offer testing to persons linked in these contact networks. For HIV-1, a rapidly evolving pathogen with low per-contact transmission rates, viral genetic sequences are an additional source of data that can be used to infer or refine transmission networks.

Methods and findings: The New York City Department of Health and Mental Hygiene interviews individuals newly diagnosed with HIV and elicits names of sexual and injection drug using partners. By law, the Department of Health also receives HIV sequences when these individuals enter healthcare and their physicians order resistance testing. Our study used both HIV sequence and partner naming data from 1342 HIV-infected persons in New York City between 2006 and 2012 to infer and compare sexual/drug-use named partner and genetic transmission networks. Using these networks, we determined a range of genetic distance thresholds suitable for identifying potential transmission partners. In 48% of cases, named partners were infected with genetically closely related viruses, compatible with but not necessarily representing or implying, direct transmission. Partner pairs linked through the genetic similarity of their HIV sequences were also linked by naming in 53% of cases. Persons who reported high-risk heterosexual contact were more likely to name at least one partner with a genetically similar virus than those reporting their risk as injection drug use or men who have sex with men.

Conclusions: We analyzed an unprecedentedly large and detailed partner tracing and HIV sequence dataset and determined an empirically justified range of genetic distance thresholds for identifying potential transmission partners. We conclude that genetic linkage provides more reliable evidence for identifying potential transmission partners than partner naming, highlighting the importance and complementarity of both epidemiological and molecular genetic surveillance for characterizing regional HIV-1 epidemics.

Fig 1. Genetic distance (Tamura-Nei 93; TN93) separating index cases and named partners.

Gray lines show the best-fitting mixture distribution. Additional tick marks indicating epidemiologically plausible thresholds between 0.01 and 0.02 substitutions/site are shown on x-axis. Blue denotes potential transmission partners (≤0.02 substitutions/site). Red denotes partners with “random” within or between subtype viral divergence.

Fig 2. Number of genetic links and transmission clusters, as a function of the TN93 distance threshold.

The epidemiologically plausible range of thresholds between 0.01 and 0.02 substitutions/site is highlighted in gray.

Fig 3. TN93 genetic distances between named partners ≤0.03 substitutions/site including and excluding codons associated with drug resistance.

Disagreement in classification (linked/unlinked) between distance models is shown in red. The line x = y is shown in solid gray. Dashed lines denote 1.75% genetic distance threshold.

Fig 4. Concordance between named partner and genetic networks.

(A) Genetic data mapped onto named partner network. Edges indicate partner naming. (B) Partner naming data mapped onto genetic network. Edges indicate genetic linkage (≤0.0175 substitutions/site).

Fig 5. Proportion of partner namings and genetic links that agree, in relation to the TN93 genetic distance threshold.

The epidemiologically plausible range of thresholds between 0.01 and 0.02 substitutions/site is highlighted in gray.

Fig 6. Genetic distance (TN93) separating index cases and named partners in select risk groups.

(A) Genetic distance between named heterosexual partners. (B) Genetic distance between named MSM partners. (C) Genetic distance between named partners where at least one partner reported injection drug use (IDU). (D) Genetic distance between named partners where at least one partner was diagnosed with acute or early HIV infection. Additional tick marks on the x-axis indicate epidemiologically plausible thresholds between 0.01 and 0.02 substitutions/site are shown on x-axis. Blue denotes potential transmission partners (≤0.02 substitutions/site). Red denotes partners with “random” within or between subtype viral divergence.