Two-year follow-up of macaques developing intermittent control of the human immunodeficiency virus homolog simian immunodeficiency virus SIVmac251 in the chronic phase of infection

Iart Luca Shytaj, Gabrielle Nickel, Eric Arts, Nicholas Farrell, Mauro Biffoni, Ranajit Pal, Hye Kyung Chung, Celia LaBranche, David Montefiori, Diego Vargas-Inchaustegui, Marjorie Robert-Guroff, Mark G. Lewis, Jonah Sacha, Anna Teresa Palamara, Andrea Savarino

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Off-therapy control of viremia by HIV-infected individuals has been associated with two likely players: a restricted viral reservoir and an efficient cell-mediated immune response. We previously showed that a combination of highly suppressive antiretroviral therapy and two experimental drugs, i.e., auranofin and buthionine sulfoximine, was able to reduce the viral reservoir, elicit efficient cell-mediated antiviral responses, and induce intermittent posttherapy viral load control in chronically SIVmac251- infected macaques. We here show that the macaques that had received this drug combination and then stopped antiretroviral therapy were also able to maintain low numbers of activated CD4+ T cells at viral rebound. Moreover, these macaques consistently displayed low-level simian immunodeficiency virus (SIV) diversity, which was in line with the strong and broadly reactive cell-mediated immune responses against conserved Gag antigens. Extended follow-up showed that the two macaques that had received the complete drug combination remained healthy and did not develop AIDS in 2 years of follow-up after therapy suspension. This disease-free survival is longer than twice the average time of progression to AIDS in SIVmac251-infected rhesus macaques. These results suggest that limited numbers of activated T cells at viral rebound and subsequent development of broadly reactive cell-mediated responses may be interrelated in reducing the viral reservoir.

Original languageEnglish (US)
Pages (from-to)7521-7535
Number of pages15
JournalJournal of Virology
Volume89
Issue number15
DOIs
StatePublished - 2015

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Human immunodeficiency virus
Macaca
HIV
combination drug therapy
therapeutics
Drug Combinations
Infection
infection
cell-mediated immunity
Acquired Immunodeficiency Syndrome
T-lymphocytes
Auranofin
Buthionine Sulfoximine
T-Lymphocytes
gag Gene Products
Investigational Therapies
Viremia
viremia

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Two-year follow-up of macaques developing intermittent control of the human immunodeficiency virus homolog simian immunodeficiency virus SIVmac251 in the chronic phase of infection. / Shytaj, Iart Luca; Nickel, Gabrielle; Arts, Eric; Farrell, Nicholas; Biffoni, Mauro; Pal, Ranajit; Chung, Hye Kyung; LaBranche, Celia; Montefiori, David; Vargas-Inchaustegui, Diego; Robert-Guroff, Marjorie; Lewis, Mark G.; Sacha, Jonah; Palamara, Anna Teresa; Savarino, Andrea.

In: Journal of Virology, Vol. 89, No. 15, 2015, p. 7521-7535.

Research output: Contribution to journalArticle

Shytaj, IL, Nickel, G, Arts, E, Farrell, N, Biffoni, M, Pal, R, Chung, HK, LaBranche, C, Montefiori, D, Vargas-Inchaustegui, D, Robert-Guroff, M, Lewis, MG, Sacha, J, Palamara, AT & Savarino, A 2015, 'Two-year follow-up of macaques developing intermittent control of the human immunodeficiency virus homolog simian immunodeficiency virus SIVmac251 in the chronic phase of infection', Journal of Virology, vol. 89, no. 15, pp. 7521-7535. https://doi.org/10.1128/JVI.00396-15
Shytaj, Iart Luca ; Nickel, Gabrielle ; Arts, Eric ; Farrell, Nicholas ; Biffoni, Mauro ; Pal, Ranajit ; Chung, Hye Kyung ; LaBranche, Celia ; Montefiori, David ; Vargas-Inchaustegui, Diego ; Robert-Guroff, Marjorie ; Lewis, Mark G. ; Sacha, Jonah ; Palamara, Anna Teresa ; Savarino, Andrea. / Two-year follow-up of macaques developing intermittent control of the human immunodeficiency virus homolog simian immunodeficiency virus SIVmac251 in the chronic phase of infection. In: Journal of Virology. 2015 ; Vol. 89, No. 15. pp. 7521-7535.
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