Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy
Abstract
The hypothesis that quiescent CD4+ T lymphocytes carrying proviral DNA provide a reservoir for human immunodeficiency virus-type 1 (HIV-1) in patients on highly active antiretroviral therapy (HAART) was examined. In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus was routinely recovered from resting CD4+ T lymphocytes. The frequency of resting CD4+ T cells harboring latent HIV-1 was low, 0.2 to 16.4 per 10(6) cells, and, in cross-sectional analysis, did not decrease with increasing time on therapy. The recovered viruses generally did not show mutations associated with resistance to the relevant antiretroviral drugs. This reservoir of nonevolving latent virus in resting CD4+ T cells should be considered in deciding whether to terminate treatment in patients who respond to HAART.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
After entering a controlled, chronic phase of HIV-1 infection, the main viral reservoir of intact proviral genomes is expected to reside in memory T cell subsets that persist for years.
“after entering a controlled, chronic phase of HIV-1 infection, the main viral reservoir of intact proviral genomes is expected to reside in memory T cell subsets that persist for years. 10-12”
From Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods (2023) · cites this paper as [10]
Cites
Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection
Chun, T.-W., Carruth, L., Finzi, D., Shen, X., DiGiuseppe, J. A., Taylor, H., Hermankova, M., Chadwick, K., Margolick, J., Quinn, T. C., et al. (1997) · Nature · doi:10.1038/387183a0 · Cited by 2,050 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Finzi, D., Blankson, J., Siliciano, J. D., Margolick, J. B., Chadwick, K., Pierson, T., Smith, K., Lisziewicz, J., Lori, F., Flexner, C., et al. (1999) · Nature Medicine · doi:10.1038/8394 · Cited by 2,119 · see citing works
Self-citationSiliciano, J. D., Kajdas, J., Finzi, D., Quinn, T. C., Chadwick, K., Margolick, J. B., Kovacs, C., Gange, S. J., & Siliciano, R. F. (2003) · Nature Medicine · doi:10.1038/nm880 · Cited by 1,703 · see citing works
Self-citationTiming the ancestor of the HIV-1 pandemic strains.
Korber, B., Muldoon, M., Theiler, J., Gao, F., Gupta, R., Lapedes, A., Hahn, B. H., Wolinsky, S., & Bhattacharya, T. (2000) · Science · doi:10.1126/science.288.5472.1789 · Cited by 1,021 · see citing works
Redefining Chronic Viral Infection
Virgin, H. W., Wherry, E. J., & Ahmed, R. (2009) · Cell · doi:10.1016/j.cell.2009.06.036 · Cited by 1,031 · see citing works
HIV reproducibly establishes a latent infection after acute infection of T cells in vitro
Jordan, A., Bisgrove, D., & Verdin, E. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg188 · Cited by 914 · see citing works
Werle–Lapostolle, B., Bowden, S., Locarnini, S., Wursthorn, K., Petersen, J., Lau, G., Trepo, C., Marcellin, P., Goodman, Z., & Delaney IV, W. E. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.03.018 · Cited by 905 · see citing works
Defective proviruses rapidly accumulate during acute HIV-1 infection
Bruner, K. M., Murray, A. J., Pollack, R. A., Soliman, M. G., Laskey, S. B., Capoferri, A. A., Lai, J., Strain, M. C., Lada, S. M., Hoh, R., et al. (2016) · Nature Medicine · doi:10.1038/nm.4156 · Cited by 737 · see citing works
Self-citationPalmer, S., Wiegand, A. P., Maldarelli, F., Bazmi, H., Mican, J. M., Polis, M., Dewar, R. L., Planta, A., Liu, S., Metcalf, J. A., et al. (2003) · Journal of Clinical Microbiology · doi:10.1128/jcm.41.10.4531-4536.2003 · Cited by 604 · see citing works
Redefining the Viral Reservoirs that Prevent HIV-1 Eradication
Eisele, E., & Siliciano, R. F. (2012) · Immunity · doi:10.1016/j.immuni.2012.08.010 · Cited by 474 · see citing works
Self-citationCytokine Signals Are Sufficient for HIV-1 Infection of Resting Human T Lymphocytes
Unutmaz, D., KewalRamani, V. N., Marmon, S., & Littman, D. R. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.11.1735 · Cited by 427 · see citing works
Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses
Einkauf, K. B., Osborn, M. R., Gao, C., Sun, W., Sun, X., Lian, X., Parsons, E. M., Gladkov, G. T., Seiger, K. W., Blackmer, J. E., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.011 · Cited by 260 · see citing works
Elliott, J. H., McMahon, J. H., Chang, C. C., Lee, S. A., Hartogensis, W., Bumpus, N., Savic, R., Roney, J., Hoh, R., Solomon, A., et al. (2015) · The Lancet HIV · doi:10.1016/s2352-3018(15)00226-x · Cited by 250 · see citing works
Abrahams, M.-R., Joseph, S. B., Garrett, N., Tyers, L., Moeser, M., Archin, N., Council, O. D., Matten, D., Zhou, S., Doolabh, D., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw5589 · Cited by 196 · see citing works
Hultquist, J. F., Schumann, K., Woo, J. M., Manganaro, L., McGregor, M. J., Doudna, J., Simon, V., Krogan, N. J., & Marson, A. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.09.080 · Cited by 170 · see citing works
HIV reservoirs: pathogenesis and obstacles to viral eradication and cure
Chun, T.-W., & Fauci, A. S. (2012) · AIDS · doi:10.1097/qad.0b013e328353f3f1 · Cited by 175 · see citing works
Qu, X., Wang, P., Ding, D., Li, L., Wang, H., Ma, L., Zhou, X., Liu, S., Lin, S., Wang, X., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt571 · Cited by 155 · see citing works
Eckstein, D. A., Sherman, M. P., Penn, M. L., Chin, P. S., De Noronha, C. M. C., Greene, W. C., & Goldsmith, M. A. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.10.1407 · Cited by 124 · see citing works
Vranckx, L. S., Demeulemeester, J., Saleh, S., Boll, A., Vansant, G., Schrijvers, R., Weydert, C., Battivelli, E., Verdin, E., Cereseto, A., et al. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.04.039 · Cited by 113 · see citing works
Selective HDAC Inhibition for the Disruption of Latent HIV-1 Infection
Barton, K. M., Archin, N. M., Keedy, K. S., Espeseth, A. S., Zhang, Y.-L., Gale, J., Wagner, F. F., Holson, E. B., & Margolis, D. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102684 · Cited by 76 · see citing works
Efficient mRNA delivery to resting T cells to reverse HIV latency
Cevaal, P. M., Kan, S., Fisher, B. M., Moso, M. A., Tan, A., Liu, H., Ali, A., Tanaka, K., Shepherd, R. A., Kim, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60001-2 · Cited by 38 · see citing works
Eradication of HIV and Cure of AIDS, Now and How?
Zhang, J., & Crumpacker, C. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00337 · Cited by 36 · see citing works
Jones, B. R., Miller, R. L., Kinloch, N. N., Tsai, O., Rigsby, H., Sudderuddin, H., Shahid, A., Ganase, B., Brumme, C. J., Harris, M., et al. (2020) · Journal of Virology · doi:10.1128/jvi.01786-19 · Cited by 29 · see citing works
Vellas, C., Nayrac, M., Collercandy, N., Requena, M., Jeanne, N., Latour, J., Dimeglio, C., Cazabat, M., Barange, K., Alric, L., et al. (2024) · eBioMedicine · doi:10.1016/j.ebiom.2023.104954 · Cited by 17 · see citing works
Su, H., Mueller, A., & Goldstein, H. (2024) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000858 · Cited by 13 · see citing works
Gallego-Cortés, A., Sánchez-Gaona, N., Mancebo-Pérez, C., Ruiz-Isant, O., Benítez-Martínez, A., Landolfi, S., Castellví, J., Pumarola, F., Ortiz, N., Llano, I., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65288-9 · Cited by 12 · see citing works
Otte, F., Zhang, Y., Spagnuolo, J., Thielen, A., Däumer, M., Wiethe, C., Stoeckle, M., Kusejko, K., Klein, F., Metzner, K. J., et al. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100485 · Cited by 4 · see citing works
Peterson, J. J., Chandel, S., James, K., Bennett, E. S., Wu, V., White, C. H., Allard, B., Clohosey, M., Whitaker, T., Baker, C., et al. (2026) · Journal of Clinical Investigation · doi:10.1172/jci196536 · Cited by 7 · see citing works
- Authors
- Finzi, D., Hermankova, M., Pierson, T., Carruth, L. M., Buck, C., Chaisson, R. E., Quinn, T. C., Chadwick, K., Margolick, J., Brookmeyer, R., Gallant, J., Markowitz, M., Ho, D. D., Richman, D. D., & Siliciano, R. F.
- Affiliations
- Johns Hopkins University (US)
- D. Finzi, M. Hermankova, T. Pierson, L. M. Carruth, C. Buck, R. E. Chaisson, T. C. Quinn, J. Gallant, R. F. Siliciano, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
- Corresponding author
- Siliciano, Robert F.
- ORCID
- Venue
- Science
- Published
- 1997-11-14
- Volume
- 278
- Issue
- 5341
- Pages
- 1295-1300
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2139250164
- Cited by
- 3,098
- References
- 1
- Citations by year
- 2026: 81 · 2025: 102 · 2024: 103 · 2023: 115 · 2022: 118 · 2021: 124 · 2020: 160 · 2019: 125 · 2018: 140 · 2017: 117 · 2016: 108 · 2015: 115 · 2014: 110 · 2013: 99 · 2012: 85
- FWCI
- 45.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ai023871-03)
- National Institute of Allergy and Infectious Diseases (AI-28108, AI23871, U01AI027670, AI2-7670)
- 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 › Surgery › Infectious Diseases and Tuberculosis
- Keywords
- HIV-1 reservoir, latent HIV-1, proviral DNA, highly active antiretroviral therapy, replication-competent virus, antiretroviral resistance, treatment discontinuation, viral persistence
- MeSH terms
- Cell Separation, Cross-Sectional Studies, Drug Resistance, Microbial, Drug Therapy, Combination, Humans, Immunologic Memory, Lymphocyte Activation, Mutation, Proviruses, RNA, Viral, Time Factors, Viremia, Virus Replication, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Virus Integration, Virus Latency, Anti-HIV Agents, Viral Load
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review