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Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication
Open accessAbstract
OBJECTIVES: Sustained suppression of plasma viremia in HIV-infected individuals is attainable with antiretroviral therapy (ART); however, eradication of virus that would allow discontinuation of ART has been hampered by the persistence of HIV reservoirs. It is of great interest to identify individuals who had received ART for prolonged periods of time with extremely low or undetectable HIV reservoirs and monitor plasma viremia following discontinuation of therapy. METHODS: We measured the size of HIV reservoirs in CD4(+) T cells of individuals on long-term ART and monitored plasma viremia following cessation of ART in one individual with an exceptionally low viral burden after a decade of therapy. RESULTS: We demonstrated undetectable levels of HIV DNA in the blood of eight of 45 infected individuals on long-term ART. Among those eight individuals, the frequency of cells carrying infectious virus was significantly lower in those who initiated ART during the early versus the chronic phase of infection. One individual with undetectable HIV DNA in both blood and tissue and a profoundly low level of infectious virus experienced plasma viral rebound 50 days following discontinuation of ART. CONCLUSIONS: Our data suggest that a significant reduction in the size of viral reservoirs may be achievable in selected individuals who initiate standard ART early in infection. However, given re-emergence of plasma viremia in an individual with an extraordinarily low viral burden, therapeutic strategies aimed at specifically targeting these extremely rare HIV-infected cells with novel interventions may be necessary in order to achieve eradication of virus.
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Cessation of therapy in HIV is associated with a strong viral rebound to pre-therapeutic plasma viral loads.
“The cessation of therapy in HIV is associated with a strong viral rebound to pre-therapeutic plasma viral loads [164,165,166]”
From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [165]
The Results report that plasma viremia rebounded after ART was stopped in one participant, reaching 1,593 and later 8,684 HIV RNA copies/ml. The Discussion says rebound is likely for the vast majority of people receiving ART. Neither passage establishes that viral loads returned to pre-therapy levels; the reported rebound was also delayed by 50 days in the participant studied. (LLM, conf=0.86)
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Research works printed but not linked: 19
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Cited by
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Hamlyn, E., Ewings, F. M., Porter, K., Cooper, D. A., Tambussi, G., Schechter, M., Pedersen, C., Okulicz, J. F., McClure, M., Babiker, A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043754 · Cited by 71
Current State of Therapeutics for HTLV-1
Wang, T. T., Hirons, A., Doerflinger, M., Morris, K. V., Ledger, S., Purcell, D. F. J., Kelleher, A. D., & Ahlenstiel, C. L. (2024) · Viruses · doi:10.3390/v16101616 · Cited by 22
Metadata
- Authors
- Chun, T.-W., Justement, J. S., Murray, D., Hallahan, C. W., Maenza, J., Collier, A. C., Sheth, P. M., Kaul, R., Ostrowski, M., Moir, S., Kovacs, C., & Fauci, A. S.
- Affiliations
- National Institutes of Health (US)
- University of Washington (US)
- University of Toronto (CA)
- Corresponding author
- Chun, Tae-Wook
- ORCID
- Venue
- AIDS
- Published
- 2010-11-27
- Volume
- 24
- Issue
- 18
- Pages
- 2803-2808
- ISSN
- 0269-9370 (ISSN-L)
- PMC
- PMC3154092
- OpenAlex
- W2080481845
- Cited by
- 276
- References
- 0
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 16 · 2023: 16 · 2022: 11 · 2021: 23 · 2020: 17 · 2019: 19 · 2018: 15 · 2017: 13 · 2016: 16 · 2015: 25 · 2014: 25 · 2013: 26 · 2012: 19
- FWCI
- 7.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- AIDS (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5u01ai041535-04)
- National Institute of Allergy and Infectious Diseases (AI57005, Z01AI000851, AI 41535, P01AI057005)
- National Center for Research Resources (M01-RR 00037, M01RR000037)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Keywords
- HIV reservoir, antiretroviral therapy discontinuation, HIV eradication, CD4+ T cells, HIV DNA, viral rebound, HIV cure
- MeSH terms
- Female, Humans, Male, RNA, Viral, Viremia, Virus Replication, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Virus Latency, Reverse Transcriptase Polymerase Chain Reaction, Antiretroviral Therapy, Highly Active, Withholding Treatment
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