Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jul;24(7):923-926.
doi: 10.1038/s41591-018-0026-6. Epub 2018 Jun 11.

Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection

Donn J Colby  1 , Lydie Trautmann  2   3 , Suteeraporn Pinyakorn  2   3 , Louise Leyre  4 , Amélie Pagliuzza  4 , Eugène Kroon  1 , Morgane Rolland  2   3 , Hiroshi Takata  2   3 , Supranee Buranapraditkun  2   3   5   6 , Jintana Intasan  1 , Nitiya Chomchey  1 , Roshell Muir  7 , Elias K Haddad  7 , Sodsai Tovanabutra  2   3 , Sasiwimol Ubolyam  8 , Diane L Bolton  2   3 , Brandie A Fullmer  9 , Robert J Gorelick  9 , Lawrence Fox  10 , Trevor A Crowell  2   3 , Rapee Trichavaroj  11 , Robert O'Connell  11 , Nicolas Chomont  4 , Jerome H Kim  2   12 , Nelson L Michael  2 , Merlin L Robb  2   3 , Nittaya Phanuphak  1 , Jintanat Ananworanich  13   14   15   16 ; RV411 study group
Collaborators, Affiliations

Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection

Donn J Colby et al. Nat Med. 2018 Jul.

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.

PubMed Disclaimer

Conflict of interest statement

COMPETING FINANCIAL INTERESTS

TC has received a speaker’s fee from Gilead. JA has received honorarium for participating in advisory meetings from Merck, Roche, AbbVie and ViiV Healthcare. All other authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Viral load (VL) rebound following ATI in eight Fiebig I acutely treated participants. (a) Median (range) time to VL rebound >20 copies/ml was 26 (13-48) days. (b) Pre-ATI peripheral blood CD4+ T/CD8 ratio ≤1 was associated with faster time to VL rebound >20 copies/ml after ATI. (c) HIV-1 phylogenetic trees based on pro- rt sequences sampled in acute infection (F, gray) and following VL rebound (R, black). The number of mutations away from the founder consensus is figured as a suffix.
Figure 2
Figure 2
Longitudinal HIV reservoir markers and immune responses. (a) Frequencies of peripheral blood CD4+ T cells harboring total HIV DNA after ART resumption were not different to baseline values. (b) Total HIV DNA in CD4+ T cells prior to ATI was not significantly associated with time to VL rebound > 20 copies/ml post-ATI. Open symbols depict levels below the limit of detection of the assay. (c) Effector Ki67+CD8+ T cells expanded rapidly following VL rebound in all participants. (d) Envelope (ENV)-specific IgG levels were higher following VL rebound in 4 of 8 participants (4617, 6054, 6579, 4320). (e) The frequencies of Ki67+CD8+ T cells and (f) plasma ENV-IgG levels were negatively associated with the highest observed viral load levels at ART resumption.
See this image and copyright information in PMC

References

MANUSCRIPT REFERENCES

    1. Finzi D, et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science (New York, NY) 1997;278:1295–1300. - PubMed
    1. Chun TW, et al. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proceedings of the National Academy of Sciences of the United States of America. 1997;94:13193–13197. - PMC - PubMed
    1. Chomont N, et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009;15:893–900. doi: 10.1038/nm.1972. - DOI - PMC - PubMed
    1. 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 pathogens. 2013;9:e1003211. doi: 10.1371/journal.ppat.1003211. - DOI - PMC - PubMed
    1. Schuetz A, et al. Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. PLoS pathogens. 2014;10:e1004543. doi: 10.1371/journal.ppat.1004543. - DOI - PMC - PubMed

ONLINE METHODS REFERENCES

    1. De Souza MS, et al. Impact of nucleic acid testing relative to antigen/antibody combination immunoassay on the detection of acute HIV infection. AIDS (London, England) 2015;29:793–800. doi: 10.1097/QAD.0000000000000616. - DOI - PubMed
    1. Fiebig EW, et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS (London, England) 2003;17:1871–1879. doi: 10.1097/01.aids.0000076308.76477.b8. - DOI - PubMed
    1. 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. 2014;9:e116306. doi: 10.1371/journal.pone.0116306. - DOI - PMC - PubMed
    1. 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. 2003;41:4531–4536. - PMC - PubMed
    1. 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. Journal of virological methods. 2009;159:185–193. doi: 10.1016/j.jviromet.2009.03.016. - DOI - PMC - PubMed

Publication types