Abstract
Antiretroviral therapy during the earliest stage of acute HIV infection (Fiebig I) might minimize establishment of a latent HIV reservoir and thereby facilitate viremic control after analytical treatment interruption. We show that 8 participants, who initiated treatment during Fiebig I and were treated for a median of 2.8 years, all experienced rapid viral load rebound following analytical treatment interruption, indicating that additional strategies are required to control or eradicate HIV.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection
Nature Communications Open Access 12 July 2022
-
Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound
Scientific Reports Open Access 10 January 2022
-
Ethical considerations for HIV remission clinical research involving participants diagnosed during acute HIV infection
BMC Medical Ethics Open Access 28 December 2021
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 per month
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Get just this article for as long as you need it
$39.95
Prices may be subject to local taxes which are calculated during checkout
Change history
05 September 2018
In the version of this article originally published, the accession codes in the Data Availability section of the Methods were not linked correctly. The original URLs were https://www.ncbi.nlm.nih.gov/genbank/mf957336/ for MF957336 and https://www.ncbi.nlm.nih.gov/genbank/mf957707/ for MF957707; they should have been https://www.ncbi.nlm.nih.gov/nuccore/MF957336 and https://www.ncbi.nlm.nih.gov/nuccore/MF957707, respectively. The error has been corrected.
References
Finzi, D. et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278, 1295–1300 (1997).
Chun, T. W. et al. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc. Natl Acad. Sci. USA 94, 13193–13197 (1997).
Chomont, N. et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat. Med. 15, 893–900 (2009).
Saez-Cirion, A. et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog. 9, e1003211 (2013).
Schuetz, A. et al. Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. PLoS Pathog. 10, e1004543 (2014).
Takata, H. et al. Delayed differentiation of potent effector CD8+ T cells reducing viremia and reservoir seeding in acute HIV infection. Sci. Transl. Med. 9, eaag1809 (2017).
Hurst, J. et al. Immunological biomarkers predict HIV-1 viral rebound after treatment interruption. Nat. Commun. 6, 8495 (2015).
Simonetti, F. R. et al. Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo. Proc. Natl Acad. Sci. USA 113, 1883–1888 (2016).
Wagner, T. A. et al. HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection. Science 345, 570–573 (2014).
Williams, J. P. et al. HIV-1 DNA predicts disease progression and post-treatment virological control. Elife 3, e03821 (2014).
Conway, J. M. & Perelson, A. S. Post-treatment control of HIV infection. Proc. Natl Acad. Sci. USA 112, 5467–5472 (2015).
Hill, A. L., Rosenbloom, D. I., Fu, F., Nowak, M. A. & Siliciano, R. F. Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1. Proc. Natl Acad. Sci. USA 111, 13475–13480 (2014).
Rothenberger, M. K. et al. Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption. Proc. Natl Acad. Sci. USA 112, E1126–1134 (2015).
Bruner, K. M. et al. Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat. Med. 22, 1043–1049 (2016).
Sneller, M. C. et al. A randomized controlled safety/efficacy trial of therapeutic vaccination in HIV-infected individuals who initiated antiretroviral therapy early in infection. Sci. Transl. Med. 9, eaan8848 (2017).
Deeks, S. G. et al. International AIDS Society global scientific strategy: towards an HIV cure 2016. Nat. Med. 22, 839–850 (2016).
Hessell, A. J. et al. Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques. Nat. Med. 22, 362–368 (2016).
Byrareddy, S. N. et al. Sustained virologic control in SIV+ macaques after antiretroviral and alpha4beta7 antibody therapy. Science 354, 197–202 (2016).
Bar, K. J. et al. Effect of HIV antibody VRC01 on viral rebound after treatment interruption. N. Engl. J. Med. 375, 2037–2050 (2016).
De Souza, M. S. et al. Impact of nucleic acid testing relative to antigen/antibody combination immunoassay on the detection of acute HIV infection. AIDS 29, 793–800 (2015).
Fiebig, E. W. et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 17, 1871–1879 (2003).
Somsouk, M. et al. The immunologic effects of mesalamine in treated HIV-infected individuals with incomplete CD4+ T cell recovery: a randomized crossover trial. PloS One 9, e116306 (2014).
Palmer, S. et al. New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J. Clin. Microbiol. 41, 4531–4536 (2003).
Land, S. et al. TREAT Asia Quality Assessment Scheme (TAQAS) to standardize the outcome of HIV genotypic resistance testing in a group of Asian laboratories. J. Virol. Meth. 159, 185–193 (2009).
Rhee, S. Y. et al. Mutational correlates of virological failure in individuals receiving a WHO-recommended tenofovir-containing first-line regimen: an international collaboration. EBioMedicine 18, 225–235 (2017).
Heipertz, R. A.Jr. et al. Molecular epidemiology of early and acute HIV type 1 infections in the United States Navy and Marine Corps, 2005-2010. AIDS Res. Hum. Retroviruses 29, 1310–1320 (2013).
Salazar-Gonzalez, J. F. et al. Deciphering human immunodeficiency virus type 1 transmission and early envelope diversification by single-genome amplification and sequencing. J. Virol. 82, 3952–3970 (2008).
Vandergeeten, C. et al. Cross-clade ultrasensitive PCR-based assays to measure HIV persistence in large-cohort studies. J. Virol. 88, 12385–12396 (2014).
Procopio, F. A. et al. a novel assay to measure the magnitude of the inducible viral reservoir in HIV-infected individuals. EBioMedicine 2, 872–881 (2015).
Deleage, C. et al. Defining HIV and SIV reservoirs in lymphoid tissues. Pathog. Immun. 1, 68–106 (2016).
Dominguez, M. H. et al. Highly multiplexed quantitation of gene expression on single cells. J. Immunol. Meth. 391, 133–145 (2013).
Bolton, D. L. et al. Combined single-cell quantitation of host and SIV genes and proteins ex vivo reveals host-pathogen interactions in individual cells. PLoS Pathog. 13, e1006445 (2017).
Altman, J. D. et al. Phenotypic analysis of antigen-specific T lymphocytes. Science. 1996. 274: 94–96. J. Immunol. 187, 7–9 (2011).
Cubas, R. A. et al. Inadequate T follicular cell help impairs B cell immunity during HIV infection. Nat. Med. 19, 494–499 (2013).
Muir, R. et al. Altered memory circulating t follicular helper-B cell interaction in early acute HIV infection. PLoS Pathog. 12, e1005777 (2016).
Acknowledgements
We are grateful to the participants who have made this research possible. We thank T. Schacker for providing data on the lymph nodes from one participant. This work was supported by the NIH grant R01AI108433, a cooperative agreement (W81XWH-07-2- 0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. and the U.S. Department of Defense (DoD), the Division of AIDS at the U.S. National Institute of Allergy and Infectious Diseases, and by an intramural grant from the Thai Red Cross AIDS Research Centre. The US Army Medical Research Acquisition Activity (820 Chandler Street, Fort Detrick, MD 21702-5014, USA) is the awarding and administering acquisition office for the cooperative agreement. It is also supported in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. Antiretroviral therapy was supported by the Thai Government Pharmaceutical Organization, Gilead, Merck and ViiV Healthcare. The views expressed are those of the authors. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, the US Army, or the Department of Defense, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government, including the US National Institutes of Health.
Author information
Authors and Affiliations
Consortia
Contributions
D.J.C., E.K., L.F., T.A.C., R.O.C., J.H.K., N.L.M., M.L.R., N.P., and J.A. designed the study. S.P. designed and performed the statistical analyses. L.T., L.L., A.P., M.R., H.T., S.B., R.M., E.K.H., S.T., S.U., D.L.B., B.A.F., R.J.G., R.T., and N. Chomont designed and performed the laboratory experiments. D.J.C. and J.A. led the study, with support from E.K., J.I. and N. Chomchey in managing the study. J.A. drafted the manuscript. All authors reviewed the manuscript, provided feedback, and approved the manuscript in its final form.
Corresponding author
Ethics declarations
Competing interests
T.A.C. has received a speaker’s fee from Gilead. J.A. has received honorarium for participating in advisory meetings from Merck, Roche, AbbVie, Gilead, and ViiV Healthcare. P.D. is an employee of EMMES corporation. All other authors declare no competing financial interests.
Additional information
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–12 and Supplementary Tables 1 and 2
Rights and permissions
About this article
Cite this article
Colby, D.J., Trautmann, L., Pinyakorn, S. et al. Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection. Nat Med 24, 923–926 (2018). https://doi.org/10.1038/s41591-018-0026-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41591-018-0026-6
This article is cited by
-
Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus
Nature Microbiology (2023)
-
CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection
Nature Communications (2022)
-
Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound
Scientific Reports (2022)
-
HIV Compartmentalization in the CNS and Its Impact in Treatment Outcomes and Cure Strategies
Current HIV/AIDS Reports (2022)
-
Viral and Host Biomarkers of HIV Remission Post Treatment Interruption
Current HIV/AIDS Reports (2022)
