Long-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells
Hiroshi Takata, Juyeon C. Kakazu, Julie L. Mitchell, Eugène Kroon, Donn Colby, Carlo Sacdalan, Hongjun Bai, Philip K. Ehrenberg, Aviva Geretz, Supranee Buranapraditkun, Suteeraporn Pinyakorn, Jintana Intasan, Somporn Tipsuk, Duanghathai Suttichom, Peeriya Prueksakaew, Thep Chalermchai, Nitiya Chomchey, Nittaya Phanuphak, Mark de Souza, Nelson L. Michael, Merlin L. Robb, Elias K. Haddad, Trevor A. Crowell, Sandhya Vasan, Victor Valcour, Daniel C. Douek, Rasmi Thomas, Morgane Rolland, Nicolas Chomont, Jintanat Ananworanich, Lydie Trautmann, Nipat Teeratakulpisarn, Supanit Pattanachaiwit, Somchai Sriplienchan, Ponpen Tantivitayakul, Ratchapong Kanaprach, Kiat Ruxrungtham, Netsiri Dumrongpisutikul, Ponlapat Rojnuckarin, Suthat Chottanapund, Kultida Poltavee, Tassanee Luekasemsuk, Hathairat Savadsuk, Suwanna Puttamsawin, Khunthalee Benjapornpong, Nisakorn Ratnaratorn, Kamonkan Tangnaree, Chutharat Munkong, Rommanus Thaimanee, Patcharin Eamyoung, Sasiwimol Ubolyam, Sukalya Lerdlum, Sopark Manasnayakorn, Rugsun Rerknimitr, Sunee Sirivichayakul, Phandee Wattanaboonyongcharoen, Jessica Cowden, Alexandra Schuetz, Siriwat Akapirat, Nampueng Churikanont, Saowanit Getchalarat, Denise C. Hsu, Esra Abacı Türk, Oratai Butterworth, Mark Milazzo, Leigh Anne Eller, Julie A. Ake, Leigh Anne Eller, Serena Spudich, CAPT Lawrence Fox, Silvia Ratto‐Kim, Victor DeGruttola, Yotin Chinvarun, Pasiri Sithinamsuwan, James L. K. Fletcher, Bruce Shiramizu, Alexandra Schuetz
Abstract
BACKGROUND: T cells become dysfunctional without treatment, antiretroviral therapy (ART) partially restores their function. However, the extent of this recovery under long-term ART is less understood. METHODS: T cells after long-term ART initiated in acute or chronic HIV infection ex vivo and upon in vitro recall. FINDINGS: T cells lacking stemness properties and exhibiting residual dysfunction upon recall, with reduced proliferation and cytolytic activity. INTERPRETATION: T cell numbers and induce stem cell-like properties to reverse the residual dysfunction persisting on ART in people treated after acute infection prior to ART release. FUNDING: U.S. National Institutes of Health and U.S. Department of Defense.