The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Ex vivo analysis identifies effective HIV-1 latency–reversing drug combinations
Open accessAbstract
Reversal of HIV-1 latency by small molecules is a potential cure strategy. This approach will likely require effective drug combinations to achieve high levels of latency reversal. Using resting CD4+ T cells (rCD4s) from infected individuals, we developed an experimental and theoretical framework to identify effective latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular HIV-1 mRNA and virion production, we compared 2-drug combinations of leading candidate LRAs and identified multiple combinations that effectively reverse latency. We showed that protein kinase C agonists in combination with bromodomain inhibitor JQ1 or histone deacetylase inhibitors robustly induce HIV-1 transcription and virus production when directly compared with maximum reactivation by T cell activation. Using the Bliss independence model to quantitate combined drug effects, we demonstrated that these combinations synergize to induce HIV-1 transcription. This robust latency reversal occurred without release of proinflammatory cytokines by rCD4s. To extend the clinical utility of our findings, we applied a mathematical model that estimates in vivo changes in plasma HIV-1 RNA from ex vivo measurements of virus production. Our study reconciles diverse findings from previous studies, establishes a quantitative experimental approach to evaluate combinatorial LRA efficacy, and presents a model to predict in vivo responses to LRAs.
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Cites
Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy
Finzi, D., Hermankova, M., Pierson, T., Carruth, L. M., Buck, C., Chaisson, R. E., Quinn, T. C., Chadwick, K., Margolick, J., Brookmeyer, R., et al. (1997) · Science · doi:10.1126/science.278.5341.1295 · Cited by 3,098
Self-citationRecovery of replication-competent HIV despite prolonged suppression of plasma viremia
Wong, J. K., Hezareh, M., Günthard, H. F., Havlir, D. V., Ignacio, C. C., Spina, C. A., & Richman, D. D. (1997) · Science · doi:10.1126/science.278.5341.1291 · Cited by 2,186
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
Self-citationQuantification 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
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
Self-citationDoyon, G., Zerbato, J., Mellors, J. W., & Sluis-Cremer, N. (2013) · AIDS · doi:10.1097/qad.0b013e3283570620 · Cited by 107
Cited by
International AIDS Society global scientific strategy: towards an HIV cure 2016
International AIDS Society Towards a Cure Working Group, Deeks, S. G., Lewin, S. R., Ross, A. L., Ananworanich, J., Benkirane, M., Cannon, P., Chomont, N., Douek, D., Lifson, J. D., et al. (2016) · Nature Medicine · doi:10.1038/nm.4108 · Cited by 425
Self-citationResearch priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021
Deeks, S. G., Archin, N., Cannon, P., Collins, S., Jones, R. B., de Jong, M. A. W. P., Lambotte, O., Lamplough, R., Ndung’u, T., Sugarman, J., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01590-5 · Cited by 377
Darcis, G., Kula, A., Bouchat, S., Fujinaga, K., Corazza, F., Ait-Ammar, A., Delacourt, N., Melard, A., Kabeya, K., Vanhulle, C., et al. (2015) · PLOS Pathogens · doi:10.1371/journal.ppat.1005063 · Cited by 281
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
Ait-Ammar, A., Kula, A., Darcis, G., Verdikt, R., De Wit, S., Gautier, V., Mallon, P. W. G., Marcello, A., Rohr, O., & Van Lint, C. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.03060 · Cited by 163
Metadata
- Authors
- Laird, G. M., Bullen, C. K., Rosenbloom, D. I. S., Martin, A. R., Hill, A. L., Durand, C. M., Siliciano, J. D., & Siliciano, R. F.
- Venue
- Journal of Clinical Investigation
- Published
- 2015-03-30
- Volume
- 125
- Issue
- 5
- Pages
- 1901-1912
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1974488636
- Cited by
- 391
- References
- 6
- FWCI
- 28.34
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Laird, G. M., Bullen, C. K., Rosenbloom, D. I. S., Martin, A. R., Hill, A. L., Durand, C. M., Siliciano, J. D., & Siliciano, R. F. (2015). Ex vivo analysis identifies effective HIV-1 latency–reversing drug combinations. Journal of Clinical Investigation. https://doi.org/10.1172/jci80142
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