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Low Multiplicity of HIV-1 Infection and No Vaccine Enhancement in VAX003 Injection Drug Users
BACKGROUND: We performed human immunodeficiency virus type 1 (HIV-1) transmitted/founder (T/F) virus analysis of the VAX003 vaccine efficacy trial participants to characterize the transmission bottleneck and test for vaccine-associated reduction or enhancement of infection in this injection drug us...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281816/ https://www.ncbi.nlm.nih.gov/pubmed/25734126 http://dx.doi.org/10.1093/ofid/ofu056 |
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author | Sterrett, Sarah Learn, Gerald H. Edlefsen, Paul T. Haynes, Barton F. Hahn, Beatrice H. Shaw, George M. Bar, Katharine J. |
author_facet | Sterrett, Sarah Learn, Gerald H. Edlefsen, Paul T. Haynes, Barton F. Hahn, Beatrice H. Shaw, George M. Bar, Katharine J. |
author_sort | Sterrett, Sarah |
collection | PubMed |
description | BACKGROUND: We performed human immunodeficiency virus type 1 (HIV-1) transmitted/founder (T/F) virus analysis of the VAX003 vaccine efficacy trial participants to characterize the transmission bottleneck and test for vaccine-associated reduction or enhancement of infection in this injection drug user (IDU) cohort. METHODS: We performed single genome sequencing of plasma vRNA from 50 subjects sampled in early HIV infection. Sequences were analyzed phylogenetically, T/F viruses enumerated, and a sieve analysis performed. RESULTS: Eight of 19 (42%) placebo recipients were productively infected by more than 1 virus (range 1–5, median 1, mean 1.7). This frequency of multiple virus transmission was greater than reported for heterosexual cohorts (19%, P = .03) but not statistically different from vaccine recipients (22.6%, P > .05), where the range was 1–3, median 1, and mean 1.3 (P > .05 for all comparisons). An atypical sieve effect was detected in Env V2 but was not associated with reduction or enhancement of virus acquisition. CONCLUSIONS: The number of T/F viruses in IDUs was surprising low, with 95% of individuals infected by only 1–3 viruses. This finding suggests that a successful vaccine or other prevention modality generally needs to protect against only one or a few viruses regardless of risk behavior. T/F analysis identified an atypical genetic sieve in the V2 region of Envelope and found no evidence for vaccine-mediated enhancement in VAX003. |
format | Online Article Text |
id | pubmed-4281816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-42818162015-03-02 Low Multiplicity of HIV-1 Infection and No Vaccine Enhancement in VAX003 Injection Drug Users Sterrett, Sarah Learn, Gerald H. Edlefsen, Paul T. Haynes, Barton F. Hahn, Beatrice H. Shaw, George M. Bar, Katharine J. Open Forum Infect Dis Major Articles BACKGROUND: We performed human immunodeficiency virus type 1 (HIV-1) transmitted/founder (T/F) virus analysis of the VAX003 vaccine efficacy trial participants to characterize the transmission bottleneck and test for vaccine-associated reduction or enhancement of infection in this injection drug user (IDU) cohort. METHODS: We performed single genome sequencing of plasma vRNA from 50 subjects sampled in early HIV infection. Sequences were analyzed phylogenetically, T/F viruses enumerated, and a sieve analysis performed. RESULTS: Eight of 19 (42%) placebo recipients were productively infected by more than 1 virus (range 1–5, median 1, mean 1.7). This frequency of multiple virus transmission was greater than reported for heterosexual cohorts (19%, P = .03) but not statistically different from vaccine recipients (22.6%, P > .05), where the range was 1–3, median 1, and mean 1.3 (P > .05 for all comparisons). An atypical sieve effect was detected in Env V2 but was not associated with reduction or enhancement of virus acquisition. CONCLUSIONS: The number of T/F viruses in IDUs was surprising low, with 95% of individuals infected by only 1–3 viruses. This finding suggests that a successful vaccine or other prevention modality generally needs to protect against only one or a few viruses regardless of risk behavior. T/F analysis identified an atypical genetic sieve in the V2 region of Envelope and found no evidence for vaccine-mediated enhancement in VAX003. Oxford University Press 2014-08-14 /pmc/articles/PMC4281816/ /pubmed/25734126 http://dx.doi.org/10.1093/ofid/ofu056 Text en © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. |
spellingShingle | Major Articles Sterrett, Sarah Learn, Gerald H. Edlefsen, Paul T. Haynes, Barton F. Hahn, Beatrice H. Shaw, George M. Bar, Katharine J. Low Multiplicity of HIV-1 Infection and No Vaccine Enhancement in VAX003 Injection Drug Users |
title | Low Multiplicity of HIV-1 Infection and No Vaccine Enhancement in VAX003 Injection Drug Users |
title_full | Low Multiplicity of HIV-1 Infection and No Vaccine Enhancement in VAX003 Injection Drug Users |
title_fullStr | Low Multiplicity of HIV-1 Infection and No Vaccine Enhancement in VAX003 Injection Drug Users |
title_full_unstemmed | Low Multiplicity of HIV-1 Infection and No Vaccine Enhancement in VAX003 Injection Drug Users |
title_short | Low Multiplicity of HIV-1 Infection and No Vaccine Enhancement in VAX003 Injection Drug Users |
title_sort | low multiplicity of hiv-1 infection and no vaccine enhancement in vax003 injection drug users |
topic | Major Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281816/ https://www.ncbi.nlm.nih.gov/pubmed/25734126 http://dx.doi.org/10.1093/ofid/ofu056 |
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