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Antiretroviral therapy suppresses HIV replication but leaves a population of infected [CD4.sup.+] T cells with integrated proviruses. While most of these proviruses contain defects, such as deletions, some intact proviruses persist and can reinitiate viral replication. In this issue of the JCI, Duette, Hiener, and colleagues performed a tour de force proviral landscape analysis on clinical samples collected over many years with in vitro functional assays. The researchers showed that effector memory [CD4.sup.+] T cells provide partial sanctuary to intact proviruses from [CD8.sup.+] T cells and this was associated with superior Nef-mediated MHC-I downregulation relative to less mature [CD4.sup.+] T cell populations. This finding implicates differential immunoevasion as a cell-intrinsic property, influencing proviral persistence, and highlights Nef as a therapeutic target., Collecting needles from 96 haystacks The vast majority (92%-98%) of the HIV-infected cells that persist with antiretroviral therapy (ART) contain proviruses with deletions, premature stop codons, or other defects that [...]

Antiretroviral therapy during the earliest stage of acute HIV infection (Fiebig I) might minimize establishment of a latent HIV reservoir and thereby facilitate viremic control after analytical treatment interruption. We show that 8 participants, who initiated treatment during Fiebig I and were treated for a median of 2.8 years, all experienced rapid viral load rebound following analytical treatment interruption, indicating that additional strategies are required to control or eradicate HIV. Initiation of antiretroviral therapy in the first 2 weeks of HIV infection fails to prevent resurgence of virus after stopping treatment, indicating early establishment of a resilient viral reservoir., Author(s): Donn J. Colby [sup.1] , Lydie Trautmann [sup.2] [sup.3] , Suteeraporn Pinyakorn [sup.2] [sup.3] , Louise Leyre [sup.4] , Amélie Pagliuzza [sup.4] , Eugène Kroon [sup.1] , Morgane Rolland [...]