HAART-Persistent HIV-1 Latent Reservoirs: Their Origin, Mechanisms of Stability and Potential Strategies for Eradication

Joseph      Kulkosky; Stacie      Bray

Abstract

HIV-1 infection persists despite long-term administration of highly active antiretroviral therapy (HAART). The mechanism of this persistence appears to result primarily from viral infection of CD4+ T-lymphocytes that have the ability to duplicate and revert into a quiescent state. These infected resting cells are long-lived and evade immune surveillance or clearance. The inability to eradicate this class of cells, bearing the viral DNA, suggests life-long persistence of virus in HIV-1-infected individuals, even if HAART were administered for decades. This review discusses the origins and mechanisms accounting for stability of these latent HIV-1 cellular reservoirs. It further provides an overview of recent clinical trials aimed at their eradication. There have been a limited number of immune activation (IAT) trials directed at HAART-persistent, viral reservoir eradication. These trials have not resulted in purging of these highly stable viral reservoirs though results from such efforts suggest partial effects. The properties of novel compounds that might be included into IAT eradication protocols are continuing to be evaluated and their potential for inclusion into future IAT trials will be discussed.

Keywords: HIV-1 latency, HAART, immune activation therapy, CD4+ resting T-cells

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