Impact of pre-adapted HIV transmission

Jonathan M., Carlson, Microsoft Research; Victor Y., Du, University of Alabama at Birmingham; Nico, Pfeifer, Microsoft Research; Anju, Bansal, University of Alabama at Birmingham; Vincent Y.F., Tan, Microsoft Research; Karen, Power, Massachusetts General Hospital; Chanson J., Brumme, British Columbia Centre for Excellence in HIV/AIDS; Anat, Kreimer, Microsoft Research; Charles E., DeZiel, Microsoft Research; Nicolo, Fusi, Microsoft Research; Malinda, Schaefer, Emory University; Mark A., Brockman, British Columbia Centre for Excellence in HIV/AIDS; Jill, Gilmour, International AIDS Vaccine Initiative; Matt A., Price, International AIDS Vaccine Initiative; William, Kilembe, Rwanda-Zambia HIV Research Group; Richard, Haubrich, Gilead Sciences; Mina, John, Murdoch University; Simon, Mallal, Murdoch University; Roger, Shapiro, Harvard University; John, Frater, University of Oxford; P. Richard, Harrigan, British Columbia Centre for Excellence in HIV/AIDS; Thumbi, Ndung'u, Massachusetts General Hospital; Susan, Allen, Emory University; David, Heckerman, Microsoft Research; John, Sidney, La Jolla Institute for Allergy and Immunology; Todd M., Allen, Massachusetts General Hospital; Philip J.R., Goulder, University of KwaZulu-Natal; Zabrina L., Brumme, British Columbia Centre for Excellence in HIV/AIDS; Eric, Hunter, Emory University; Paul A., Goepfert, University of Alabama at Birmingham

Persistent URL

https://open.library.emory.edu/purl/443nvx0kgs-emory

Last modified

02/25/2025

Type of Material

Article

Authors

Jonathan M. Carlson, Microsoft Research

Victor Y. Du, University of Alabama at Birmingham

Nico Pfeifer, Microsoft Research

Anju Bansal, University of Alabama at Birmingham

Vincent Y.F. Tan, Microsoft Research

Karen Power, Massachusetts General HospitalChanson J. Brumme, British Columbia Centre for Excellence in HIV/AIDSAnat Kreimer, Microsoft ResearchCharles E. DeZiel, Microsoft ResearchNicolo Fusi, Microsoft ResearchMalinda Schaefer, Emory UniversityMark A. Brockman, British Columbia Centre for Excellence in HIV/AIDSJill Gilmour, International AIDS Vaccine InitiativeMatt A. Price, International AIDS Vaccine InitiativeWilliam Kilembe, Rwanda-Zambia HIV Research GroupRichard Haubrich, Gilead SciencesMina John, Murdoch UniversitySimon Mallal, Murdoch UniversityRoger Shapiro, Harvard UniversityJohn Frater, University of OxfordP. Richard Harrigan, British Columbia Centre for Excellence in HIV/AIDSThumbi Ndung'u, Massachusetts General HospitalSusan Allen, Emory UniversityDavid Heckerman, Microsoft ResearchJohn Sidney, La Jolla Institute for Allergy and ImmunologyTodd M. Allen, Massachusetts General HospitalPhilip J.R. Goulder, University of KwaZulu-NatalZabrina L. Brumme, British Columbia Centre for Excellence in HIV/AIDSEric Hunter, Emory UniversityPaul A. Goepfert, University of Alabama at Birmingham

Language

English

Date

2016-06-01

Publisher

Nature Publishing Group

Publication Version

Author Accepted Manuscript (After Peer Review)

Copyright Statement

© 2016, Rights Managed by Nature Publishing Group.

Final Published Version (URL)

http://dx.doi.org/10.1038/nm.4100

Title of Journal or Parent Work

Nature Medicine

ISSN

1078-8956

Volume

22

Issue

6

Start Page

606

End Page

+

Grant/Funding Information

This study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) grants R01 AI112566 (P.A.G.), R56 AI098551 (P.A.G.), R01 AI64060 (E.H.), R37 AI51231 (E.H.), P01 AI074415 (T.M.A.), U01 AI 66454 (R.S.), RO1 AI46995 (P.J.R.G.), and R01 AI071906 (R.A. Kaslow and J. Tang); Canadian Institutes of Health Research grants MOP-93536 (M.A.B, Z.L.B) and HOP-115700 (M.A.B., Z.L.B.); and Wellcome Trust grant WT104748MA (P.J.R.G.).
HLA typing and viral sequencing of the ACTG cohorts were supported by U01 AI068636 and by National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR).
Support for the ZEHRP cohort was also provided by the International AIDS Vaccine Initiative (S.A.), and made possible in part by the support of the American people through the U.S. Agency for International Development (USAID). A full list of IAVI donors is available at www.iavi.org.
For additional funding information, see the full article.

Supplemental Material (URL)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899163/bin/NIHMS776315-supplement-1.pdf

Abstract

Human leukocyte antigen class I (HLA)-restricted CD8 + T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-Term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we here developed a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses that are pre-Adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4 + T cell decline. Furthermore, the extent of pre-Adaptation among circulating viruses explains much of the variation in outcomes attributed to the expression of certain HLA alleles. Thus, viral pre-Adaptation exploits 'holes' in the immune response. Accounting for these holes may be key for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies that require broad CTL responses to achieve successful eradication of HIV reservoirs.

Author Notes