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Distinct mechanisms of long-term virologic control in two HIV-infected individuals after treatment interruption of anti-retroviral therapy
Nature Medicine  (IF53.44),  Pub Date : 2021-10-28, DOI: 10.1038/s41591-021-01503-6
Jana Blazkova, Feng Gao, Manukumar Honnayakanahalli Marichannegowda, J. Shawn Justement, Victoria Shi, Emily J. Whitehead, Rachel F. Schneck, Erin D. Huiting, Kathleen Gittens, Mackenzie Cottrell, Erika Benko, Colin Kovacs, Justin Lack, Michael C. Sneller, Susan Moir, Anthony S. Fauci, Tae-Wook Chun

Certain infected individuals suppress human immunodeficiency virus (HIV) in the absence of anti-retroviral therapy (ART). Elucidating the underlying mechanism(s) is of high interest. Here we present two contrasting case reports of HIV-infected individuals who controlled plasma viremia for extended periods after undergoing analytical treatment interruption (ATI). In Participant 04, who experienced viral blips and initiated undisclosed self-administration of suboptimal ART detected shortly before day 1,250, phylogenetic analyses of plasma HIV env sequences suggested continuous viral evolution and/or reactivation of pre-existing viral reservoirs over time. Antiviral CD8+ T cell activities were higher in Participant 04 than in Participant 30. In contrast, Participant 30 exhibited potent plasma-IgG-mediated neutralization activity against autologous virus that became ineffective when he experienced sudden plasma viral rebound 1,434 d after ATI due to HIV superinfection. Our data provide insight into distinct mechanisms of post-treatment interruption control and highlight the importance of frequent monitoring of undisclosed use of ART and superinfection during the ATI phase.