Using HIV Networks to Inform Real Time Prevention Interventions

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Abstract

Objective

To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission.

Design

HIV-1 pol sequence data were analyzed to infer the local transmission network.

Methods

We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions.

Results

HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p = 0.014 and p = 0.0455, respectively) and predicted risk of transmission (p<0.0001). Retrospective analysis of antiretroviral therapy (ART) use, and simulations of ART targeted to individuals with the highest TNS, showed significantly reduced network level HIV transmission (p<0.05).

Conclusions

Sequence data from an HIV-1 screening program focused on recently infected persons and their social and sexual contacts enabled the characterization of a highly connected transmission network. The network-based risk score (TNS) was highly correlated with transmission risk behaviors and outcomes, and can be used identify and target effective prevention interventions, like ART, to those at a greater risk for HIV-1 transmission.

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Most cited references 23

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New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes.

Robert Janssen (1998)

Differentiating individuals with early human immunodeficiency virus 1 (HIV-1) infection from those infected for longer periods is difficult but important for estimating HIV incidence and for purposes of clinical care and prevention. To develop and validate a serologic testing algorithm in which HIV-1-positive persons with reactive test results on a sensitive HIV-1 enzyme immunoassay (EIA) but nonreactive results on a less sensitive (LS) EIA are identified as having early infection. Diagnostic test and testing strategy development, validation, and application. Specimens were tested with both a sensitive HIV-1 EIA (3A11 assay) and a less sensitive modification of the same EIA (3A11-LS assay). For assay development: 104 persons seroconverting to HIV-1 comprising 38 plasma donors, 18 patients of a sexually transmitted disease clinic in Trinidad, and 48 participants in the San Francisco Men's Health Study (SFMHS); 268 men without the acquired immunodeficiency syndrome (AIDS) in the SFMHS who had been infected for at least 2.5 years; and 207 persons with clinical AIDS; for testing strategy validation: 488 men in the SFMHS from 1985 through 1990 and 1275449 repeat blood donors at 3 American Red Cross blood centers from 1993 through 1995; and for HIV-1 incidence estimates: 2717910 first-time blood donors. We retrospectively identified persons eligible for a study of early infection. Ability to identify early HIV infection. Estimated mean time from being 3A11 reactive/3A11-LS nonreactive to being 3A11 reactive/3A11-LS reactive was 129 days (95% confidence interval [CI], 109-149 days) [corrected]. Our testing strategy accurately diagnosed 95% of persons with early infection; however, 0.4% (1/268) of men with established infection and 2% (5/207) of persons with late-stage AIDS were misdiagnosed as having early HIV-1 infection. Average yearly incidence estimates in SFMHS subjects were 1.5% per year vs observed average incidence of 1.4 per 100 person-years. Incidence in repeat blood donors using the sensitive/less sensitive assay testing strategy was 2.95 per 100000 per year (95% CI, 1.14-6.53/100000) vs observed incidence of 2.60 per 100000 person-years (95% CI, 1.49-4.21/100000). Overall incidence in first-time blood donors was 7.18 per 100000 per year (95% CI, 4.51-11.20/100000) and did not change statistically significantly between 1993 and 1996. Use of the sensitive/less sensitive testing strategy alone would have identified all 17 persons with antibodies to HIV-1 eligible for a study of early HIV-1 infection and would have increased enrollment. The sensitive/less sensitive testing strategy provides accurate diagnosis of early HIV-1 infection, provides accurate estimates of HIV-1 incidence, can facilitate clinical studies of early HIV-1 infection, and provides information on HIV-1 infection duration for care planning.

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Transmission Network Parameters Estimated From HIV Sequences for a Nationwide Epidemic

Andrew Leigh Brown, Samantha Lycett, Lucy A. Weinert … (2011)

Background. Many studies of sexual behavior have shown that individuals vary greatly in their number of sexual partners over time, but it has proved difficult to obtain parameter estimates relating to the dynamics of human immunodeficiency virus (HIV) transmission except in small-scale contact tracing studies. Recent developments in molecular phylodynamics have provided new routes to obtain these parameter estimates, and current clinical practice provides suitable data for entire infected populations. Methods. A phylodynamic analysis was performed on partial pol gene sequences obtained for routine clinical care from 14 560 individuals, representing approximately 60% of the HIV-positive men who have sex with men (MSM) under care in the United Kingdom. Results. Among individuals linked to others in the data set, 29% are linked to only 1 individual, 41% are linked to 2–10 individuals, and 29% are linked to ≥10 individuals. The right-skewed degree distribution can be approximated by a power law, but the data are best fitted by a Waring distribution for all time depths. For time depths of 5–7 years, the distribution parameter ρ lies within the range that indicates infinite variance. Conclusions. The transmission network among UK MSM is characterized by preferential association such that a randomly distributed intervention would not be expected to stop the epidemic.

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Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection.

Michael W. Stewart, F E Martinson, Myron S Cohen … (2007)

This study was conducted to compare viral dynamics in blood and semen between subjects with antibody negative, acute HIV-1 infection and other subjects with later stages of infection. A prospective cohort study was embedded within a cross-sectional study of HIV screening in a Lilongwe, Malawi STD clinic. Blood samples from HIV antibody negative or indeterminate volunteers were used to detect HIV RNA in plasma using a pooling strategy. Blood and seminal plasma HIV-1 RNA concentrations were measured over 16 weeks. Sixteen men with acute HIV infection and 25 men with chronic HIV infection were studied. Blood viral load in subjects with acute HIV infection was highest about 17 days after infection (mean +/- SE, 6.9 +/- 0.5 log10 copies/ml), while semen viral load peaked about 30 days after infection (4.5 +/- 0.4 log10 copies/ml). Semen viral load declined by 1.7 log10 to a nadir by week 10 of HIV infection. Semen and blood viral loads were more stable in chronically infected subjects over 16 weeks. Higher semen levels of HIV RNA were noted in subjects with low CD4 cell counts. These results provide a biological explanation for reported increases in HIV transmission during the very early (acute) and late stages of infection. Recognizing temporal differences in HIV shedding in the genital tract is important in the development of effective HIV prevention strategies.

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Author and article information

Contributors

Paul Richard Harrigan: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2014

Publication date (Electronic): 5 June 2014

Volume: 9

Issue: 6

Electronic Location Identifier: e98443

Affiliations

[1 ]Department of Medicine, University of California, San Diego, La Jolla, California, United States of America

[2 ]Department of Biostatistics, University of Washington, Seattle, Washington, United States of America

[3 ]Veterans Affairs San Diego Healthcare System, San Diego, California, United States of America

University of British Columbia, Canada

Author notes

* E-mail: slittle@ 123456ucsd.edu

Competing Interests: Dr. Pond served as a consultant for Monogram Biosciences and Genprobe. Dr. Smith reported receiving grant funding from ViiV Healthcare and having served as a consultant for Genprobe and Testing Talent Services. No other competing interest disclosures were reported. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials

Conceived and designed the experiments: SJL SLKP DMS. Performed the experiments: SJL DMS. Analyzed the data: SLKP SM JOW JAY CMA SJL DMS. Contributed reagents/materials/analysis tools: CMA JAY JOW. Wrote the paper: SJL SLKP SRM DMS.

Article

Publisher ID: PONE-D-13-41095

DOI: 10.1371/journal.pone.0098443

PMC ID: 4047027

PubMed ID: 24901437

SO-VID: a0603ae5-dc27-451f-94e8-197d5b110575

License:

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

History

Date received : 8 October 2013

Date accepted : 2 May 2014

Page count

Pages: 8

Funding

This research was supported by funds from the following: National Institutes of Health grants AI43638, AI74621, AI106039, AI47745, GM093939, AI093163, MH083552, AI090970, AI96189, DA034978, AI067039, AI097061, AI100665, AI080353, MH097520, AI36214, MH62512, TW008908, AI69432, AI096113, AI47745 and California HIV-1 Research Program (CHRP) RN07-SD-702. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Using HIV Networks to Inform Real Time Prevention Interventions

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Abstract

Objective

Design

Methods

Results

Conclusions

Related collections

PLOS Climate

Most cited references 23

New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes.

Transmission Network Parameters Estimated From HIV Sequences for a Nationwide Epidemic

Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection.

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