Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Sterrett, Sarah, Learn, Gerald H., Edlefsen, Paul T., Haynes, Barton F., Hahn, Beatrice H., Shaw, George M., Bar, Katharine J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
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
_version_ 1782351041097891840
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
work_keys_str_mv AT sterrettsarah lowmultiplicityofhiv1infectionandnovaccineenhancementinvax003injectiondrugusers
AT learngeraldh lowmultiplicityofhiv1infectionandnovaccineenhancementinvax003injectiondrugusers
AT edlefsenpault lowmultiplicityofhiv1infectionandnovaccineenhancementinvax003injectiondrugusers
AT haynesbartonf lowmultiplicityofhiv1infectionandnovaccineenhancementinvax003injectiondrugusers
AT hahnbeatriceh lowmultiplicityofhiv1infectionandnovaccineenhancementinvax003injectiondrugusers
AT shawgeorgem lowmultiplicityofhiv1infectionandnovaccineenhancementinvax003injectiondrugusers
AT barkatharinej lowmultiplicityofhiv1infectionandnovaccineenhancementinvax003injectiondrugusers