TY - JOUR
T1 - 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
AU - Shytaj, Iart Luca
AU - Nickel, Gabrielle
AU - Arts, Eric
AU - Farrell, Nicholas
AU - Biffoni, Mauro
AU - Pal, Ranajit
AU - Chung, Hye Kyung
AU - LaBranche, Celia
AU - Montefiori, David
AU - Vargas-Inchaustegui, Diego
AU - Robert-Guroff, Marjorie
AU - Lewis, Mark G.
AU - Sacha, Jonah B.
AU - Palamara, Anna Teresa
AU - Savarino, Andrea
N1 - Publisher Copyright:
© 2015, American Society for Microbiology.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84937682389&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937682389&partnerID=8YFLogxK
U2 - 10.1128/JVI.00396-15
DO - 10.1128/JVI.00396-15
M3 - Article
C2 - 25972547
AN - SCOPUS:84937682389
SN - 0022-538X
VL - 89
SP - 7521
EP - 7535
JO - Journal of virology
JF - Journal of virology
IS - 15
ER -