Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques

So Yon Lim; Jina Lee; Christa E. Osuna; Pratik Vikhe; Dane R. Schalk; Elsa Chen; Emily Fray; Mithra Kumar; Nancy Schultz-Darken; Eva Rakasz; Saverio Capuano; Ruby A. Ladd; Hwi Min Gil; David T. Evans; Emily K. Jeng; Michael Seaman; Malcolm Martin; Christiaan Van Dorp; Alan S. Perelson; Hing C. Wong; Janet D. Siliciano; Robert Siliciano; Jeffrey T. Safrit; Douglas F. Nixon; Patrick Soon-Shiong; Michel Nussenzweig; James B. Whitney

doi:10.1126/science.adf7966

Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques

So Yon Lim, Jina Lee, Christa E. Osuna, Pratik Vikhe, Dane R. Schalk, Elsa Chen, Emily Fray, Mithra Kumar, Nancy Schultz-Darken, Eva Rakasz, Saverio Capuano, Ruby A. Ladd, Hwi Min Gil, David T. Evans, Emily K. Jeng, Michael Seaman, Malcolm Martin, Christiaan Van Dorp, Alan S. Perelson, Hing C. WongJanet D. Siliciano, Robert Siliciano, Jeffrey T. Safrit, Douglas F. Nixon, Patrick Soon-Shiong, Michel Nussenzweig, James B. Whitney

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Abstract

The eradication of the viral reservoir represents the major obstacle to the development of a clinical cure for established HIV-1 infection. Here, we demonstrate that the administration of N-803 (brand name Anktiva) and broadly neutralizing antibodies (bNAbs) results in sustained viral control after discontinuation of antiretroviral therapy (ART) in simian-human AD8 (SHIV-AD8)–infected, ART-suppressed rhesus macaques. N-803+bNAbs treatment induced immune activation and transient viremia but only limited reductions in the SHIV reservoir. Upon ART discontinuation, viral rebound occurred in all animals, which was followed by durable control in approximately 70% of all N-803+bNAb–treated macaques. Viral control was correlated with the reprogramming of CD8⁺ T cells by N-803+bNAb synergy. Thus, complete eradication of the replication-competent viral reservoir is likely not a prerequisite for the induction of sustained remission after discontinuation of ART.

Original language	English (US)
Pages (from-to)	1104-1111
Number of pages	8
Journal	Science
Volume	383
Issue number	6687
DOIs	https://doi.org/10.1126/science.adf7966
State	Published - Mar 8 2024

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Lim, S. Y., Lee, J., Osuna, C. E., Vikhe, P., Schalk, D. R., Chen, E., Fray, E., Kumar, M., Schultz-Darken, N., Rakasz, E., Capuano, S., Ladd, R. A., Gil, H. M., Evans, D. T., Jeng, E. K., Seaman, M., Martin, M., Dorp, C. V., Perelson, A. S., ... Whitney, J. B. (2024). Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques. Science, 383(6687), 1104-1111. https://doi.org/10.1126/science.adf7966

Lim, SY, Lee, J, Osuna, CE, Vikhe, P, Schalk, DR, Chen, E, Fray, E, Kumar, M, Schultz-Darken, N, Rakasz, E, Capuano, S, Ladd, RA, Gil, HM, Evans, DT, Jeng, EK, Seaman, M, Martin, M, Dorp, CV, Perelson, AS, Wong, HC, Siliciano, JD , Siliciano, R, Safrit, JT, Nixon, DF, Soon-Shiong, P, Nussenzweig, M & Whitney, JB 2024, 'Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques', Science, vol. 383, no. 6687, pp. 1104-1111. https://doi.org/10.1126/science.adf7966

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title = "Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques",

abstract = "The eradication of the viral reservoir represents the major obstacle to the development of a clinical cure for established HIV-1 infection. Here, we demonstrate that the administration of N-803 (brand name Anktiva) and broadly neutralizing antibodies (bNAbs) results in sustained viral control after discontinuation of antiretroviral therapy (ART) in simian-human AD8 (SHIV-AD8)–infected, ART-suppressed rhesus macaques. N-803+bNAbs treatment induced immune activation and transient viremia but only limited reductions in the SHIV reservoir. Upon ART discontinuation, viral rebound occurred in all animals, which was followed by durable control in approximately 70% of all N-803+bNAb–treated macaques. Viral control was correlated with the reprogramming of CD8+ T cells by N-803+bNAb synergy. Thus, complete eradication of the replication-competent viral reservoir is likely not a prerequisite for the induction of sustained remission after discontinuation of ART.",

author = "Lim, {So Yon} and Jina Lee and Osuna, {Christa E.} and Pratik Vikhe and Schalk, {Dane R.} and Elsa Chen and Emily Fray and Mithra Kumar and Nancy Schultz-Darken and Eva Rakasz and Saverio Capuano and Ladd, {Ruby A.} and Gil, {Hwi Min} and Evans, {David T.} and Jeng, {Emily K.} and Michael Seaman and Malcolm Martin and Dorp, {Christiaan Van} and Perelson, {Alan S.} and Wong, {Hing C.} and Siliciano, {Janet D.} and Robert Siliciano and Safrit, {Jeffrey T.} and Nixon, {Douglas F.} and Patrick Soon-Shiong and Michel Nussenzweig and Whitney, {James B.}",

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AU - Lim, So Yon

AU - Lee, Jina

AU - Osuna, Christa E.

AU - Vikhe, Pratik

AU - Schalk, Dane R.

AU - Chen, Elsa

AU - Fray, Emily

AU - Kumar, Mithra

AU - Schultz-Darken, Nancy

AU - Rakasz, Eva

AU - Capuano, Saverio

AU - Ladd, Ruby A.

AU - Gil, Hwi Min

AU - Evans, David T.

AU - Jeng, Emily K.

AU - Seaman, Michael

AU - Martin, Malcolm

AU - Dorp, Christiaan Van

AU - Perelson, Alan S.

AU - Wong, Hing C.

AU - Siliciano, Janet D.

AU - Siliciano, Robert

AU - Safrit, Jeffrey T.

AU - Nixon, Douglas F.

AU - Soon-Shiong, Patrick

AU - Nussenzweig, Michel

AU - Whitney, James B.

PY - 2024/3/8

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N2 - The eradication of the viral reservoir represents the major obstacle to the development of a clinical cure for established HIV-1 infection. Here, we demonstrate that the administration of N-803 (brand name Anktiva) and broadly neutralizing antibodies (bNAbs) results in sustained viral control after discontinuation of antiretroviral therapy (ART) in simian-human AD8 (SHIV-AD8)–infected, ART-suppressed rhesus macaques. N-803+bNAbs treatment induced immune activation and transient viremia but only limited reductions in the SHIV reservoir. Upon ART discontinuation, viral rebound occurred in all animals, which was followed by durable control in approximately 70% of all N-803+bNAb–treated macaques. Viral control was correlated with the reprogramming of CD8+ T cells by N-803+bNAb synergy. Thus, complete eradication of the replication-competent viral reservoir is likely not a prerequisite for the induction of sustained remission after discontinuation of ART.

AB - The eradication of the viral reservoir represents the major obstacle to the development of a clinical cure for established HIV-1 infection. Here, we demonstrate that the administration of N-803 (brand name Anktiva) and broadly neutralizing antibodies (bNAbs) results in sustained viral control after discontinuation of antiretroviral therapy (ART) in simian-human AD8 (SHIV-AD8)–infected, ART-suppressed rhesus macaques. N-803+bNAbs treatment induced immune activation and transient viremia but only limited reductions in the SHIV reservoir. Upon ART discontinuation, viral rebound occurred in all animals, which was followed by durable control in approximately 70% of all N-803+bNAb–treated macaques. Viral control was correlated with the reprogramming of CD8+ T cells by N-803+bNAb synergy. Thus, complete eradication of the replication-competent viral reservoir is likely not a prerequisite for the induction of sustained remission after discontinuation of ART.

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Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques

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