Journal article
Long-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells
EBioMedicine, v 84, 104253
Oct 2022
PMID: 36088683
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Harnessing CD8+ T cell responses is being explored to achieve HIV remission. Although HIV-specific CD8+ 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.
We analyzed the differentiation status and function of HIV-specific CD8+ T cells after long-term ART initiated in acute or chronic HIV infection ex vivo and upon in vitro recall.
ART initiation in any stage of acute HIV infection promoted the persistence of long-lived HIV-specific CD8+ T cells with high expansion (P<0·0008) and cytotoxic capacity (P=0·02) after in vitro recall, albeit at low cell number (P=0·003). This superior expansion capacity correlated with stemness (r=0·90, P=0·006), measured by TCF-1 expression, similar to functional HIV-specific CD8+ T cells found in spontaneous controllers. Importanly, TCF-1 expression in these cells was associated with longer time to viral rebound ranging from 13 to 48 days after ART interruption (r =0·71, P=0·03). In contrast, ART initiation in chronic HIV infection led to more differentiated HIV-specific CD8+ T cells lacking stemness properties and exhibiting residual dysfunction upon recall, with reduced proliferation and cytolytic activity.
ART initiation in acute HIV infection preserves functional HIV-specific CD8+ T cells, albeit at numbers too low to control viral rebound post-ART. HIV remission strategies may need to boost HIV-specific CD8+ 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.
U.S. National Institutes of Health and U.S. Department of Defense.
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Details
- Title
- Long-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells
- Creators
- Hiroshi Takata - Henry M. Jackson FoundationJuyeon C. Kakazu - Walter Reed Army Institute of ResearchJulie L. Mitchell - Oregon Health & Science UniversityEugene Kroon - Institut de Recherche et d’InnovationDonn J. Colby - Walter Reed Army Institute of ResearchCarlo Sacdalan - Chulalongkorn UniversityHongjun Bai - Walter Reed Army Institute of ResearchPhilip K. Ehrenberg - Walter Reed Army Institute of ResearchAviva Geretz - Walter Reed Army Institute of ResearchSupranee Buranapraditkun - Chulalongkorn UniversitySuteeraporn Pinyakorn - Walter Reed Army Institute of ResearchJintana Intasan - Institut de Recherche et d’InnovationSomporn Tipsuk - Institut de Recherche et d’InnovationDuanghathai Suttichom - Institut de Recherche et d’InnovationPeeriya Prueksakaew - Institut de Recherche et d’InnovationThep Chalermchai - Institut de Recherche et d’InnovationNitiya Chomchey - Institut de Recherche et d’InnovationNittaya Phanuphak - Search InstituteMark de Souza - Institut de Recherche et d’InnovationNelson L. Michael - Walter Reed Army Institute of ResearchMerlin L. Robb - Walter Reed Army Institute of ResearchElias K. Haddad - Drexel UniversityTrevor A Crowell - Walter Reed Army Institute of ResearchSandhya Vasan - Walter Reed Army Institute of ResearchVictor G. Valcour - University Memory and Aging CenterDaniel C. Douek - Vaccine Research CenterRasmi Thomas - Walter Reed Army Institute of ResearchMorgane Rolland - Walter Reed Army Institute of ResearchNicolas Chomont - Centre Hospitalier de l’Université de MontréalJintanat Ananworanich - Walter Reed Army Institute of ResearchLydie Trautmann - Henry M. Jackson FoundationNipat TeeratakulpisarnSupanit PattanachaiwitSomchai SriplienchanPonpen TantivitayakulRatchapong KanaprachKiat RuxrungthamNetsiri DumrongpisutikulPonlapat RojnuckarinSuthat ChottanapundKultida PoltaveeTassanee LuekasemsukHathairat SavadsukSuwanna PuttamsawinKhunthalee BenjapornpongNisakorn RatnaratornKamonkan TangnareeChutharat MunkongRommanus ThaimaneePatcharin EamyoungSasiwimol UbolyamSukalya LerdlumSopark ManasnayakornRugsun RerknimitrSunee SirivichayakulPhandee WattanaboonyongcharoenJessica CowdenAlexandra SchuetzSiriwat AkapiratNampueng ChurikanontSaowanit GetchalaratDenise HsuEllen TurkOratai ButterworthMark MilazzoLeigh Anne EllerJulie AkeSerena SpudichCAPT Lawrence FoxSilvia Ratto-KimVictor DeGruttolaYotin ChinvarunPasiri SithinamsuwanJames FletcherThe RV254/SEARCH010, RV304/ SEARCH013, and SEARCH011 study groupsBruce Shiramizu
- Publication Details
- EBioMedicine, v 84, 104253
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000877614200003
- Scopus ID
- 2-s2.0-85137405293
- Other Identifier
- 991020099456904721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Medicine, Research & Experimental