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.
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 B.; Palamara, ANNA TERESA; Savarino, Andrea. - In: JOURNAL OF VIROLOGY. - ISSN 0022-538X. - STAMPA. - 89:15(2015), pp. 7521-7535. [10.1128/JVI.00396-15]
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
PALAMARA, ANNA TERESA;
2015
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.File | Dimensione | Formato | |
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