TY - JOUR
T1 - A randomized trial of vorinostat with treatment interruption after initiating antiretroviral therapy during acute HIV-1 infection
AU - SEARCH 019 and RV254 Study Teams
AU - Kroon, Eugene D.M.B.
AU - Ananworanich, Jintanat
AU - Pagliuzza, Amelie
AU - Rhodes, Ajantha
AU - Phanuphak, Nittaya
AU - Trautmann, Lydie
AU - Mitchell, Julie L.
AU - Chintanaphol, Michelle
AU - Intasan, Jintana
AU - Pinyakorn, Suteeraporn
AU - Benjapornpong, Khuntalee
AU - Judy Chang, J.
AU - Colby, Donn J.
AU - Chomchey, Nitiya
AU - Fletcher, James L.K.
AU - Eubanks, Keith
AU - Yang, Hua
AU - Kapson, John
AU - Dantanarayana, Ashanti
AU - Tennakoon, Surekha
AU - Gorelick, Robert J.
AU - Maldarelli, Frank
AU - Robb, Merlin L.
AU - Kim, Jerome H.
AU - Spudich, Serena
AU - Chomont, Nicolas
AU - Phanuphak, Praphan
AU - Lewin, Sharon R.
AU - de Souza, Mark S.
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/9
Y1 - 2020/9
N2 - Objective and Design: A randomized, open-label pilot study in individuals treated with antiretroviral therapy (ART) since acute HIV infection (AHI) with a regimen including a histone deacetylase inhibitor to induce HIV from latency and control HIV replication during subsequent treatment interruption (TI). Methods: Fifteen participants who initiated ART at AHI were randomized to vorinostat/hydroxychloroquine/ maraviroc (VHM) plus ART (n ¼ 10) or ART alone (n ¼ 5). The VHM arm received three 14-day vorinostat cycles within 10 weeks before TI. ART was resumed for plasma viral load (VL) > 1,000 HIV RNA copies/mL. Primary outcome was proportion of participants on VHM þ ART versus ART only with VL < 50 copies/mL for 24 weeks after TI. Results: Fifteen participants on ART (median: 178 weeks: range 79–295) enrolled. Two on VHM þ ART experienced serious adverse events. Fourteen participants underwent TI; all experienced VL rebound with no difference in time between arms: VHM þ ART (n ¼ 9) median: 4 weeks and ART only (n ¼ 5) median: 5 weeks. VHM induced a 2.2-fold increase in VL (p ¼ 0.008) by single-copy HIV RNA assay after the first cycle. Neopterin levels increased significantly following the first two cycles. After VHM treatment, the frequencies of peripheral blood mononuclear cells harboring total HIV DNA and cell-associated RNA were unchanged. All participants achieved VL suppression following ART re-initiation. Conclusions: Administration of VHM increased HIV VL in plasma, but this was not sustained. VHM did not impact time to viral rebound following TI and had no impact on the size of the HIV reservoir, suggesting that HIV reservoir elimination will require alternative treatment strategies.
AB - Objective and Design: A randomized, open-label pilot study in individuals treated with antiretroviral therapy (ART) since acute HIV infection (AHI) with a regimen including a histone deacetylase inhibitor to induce HIV from latency and control HIV replication during subsequent treatment interruption (TI). Methods: Fifteen participants who initiated ART at AHI were randomized to vorinostat/hydroxychloroquine/ maraviroc (VHM) plus ART (n ¼ 10) or ART alone (n ¼ 5). The VHM arm received three 14-day vorinostat cycles within 10 weeks before TI. ART was resumed for plasma viral load (VL) > 1,000 HIV RNA copies/mL. Primary outcome was proportion of participants on VHM þ ART versus ART only with VL < 50 copies/mL for 24 weeks after TI. Results: Fifteen participants on ART (median: 178 weeks: range 79–295) enrolled. Two on VHM þ ART experienced serious adverse events. Fourteen participants underwent TI; all experienced VL rebound with no difference in time between arms: VHM þ ART (n ¼ 9) median: 4 weeks and ART only (n ¼ 5) median: 5 weeks. VHM induced a 2.2-fold increase in VL (p ¼ 0.008) by single-copy HIV RNA assay after the first cycle. Neopterin levels increased significantly following the first two cycles. After VHM treatment, the frequencies of peripheral blood mononuclear cells harboring total HIV DNA and cell-associated RNA were unchanged. All participants achieved VL suppression following ART re-initiation. Conclusions: Administration of VHM increased HIV VL in plasma, but this was not sustained. VHM did not impact time to viral rebound following TI and had no impact on the size of the HIV reservoir, suggesting that HIV reservoir elimination will require alternative treatment strategies.
KW - Acute HIV infection
KW - HIV remission
KW - Latency reversal
KW - Maraviroc
KW - Vorinostat
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U2 - 10.1016/j.jve.2020.100004
DO - 10.1016/j.jve.2020.100004
M3 - Article
AN - SCOPUS:85090598495
SN - 2055-6640
VL - 6
JO - Journal of Virus Eradication
JF - Journal of Virus Eradication
IS - 3
M1 - 100004
ER -