H-106 Sustained ART-free HIV remission: Obstacles and opportunities

Abstract

Profound and durable suppression of HIV by antiretroviral therapy (ART) represents a major accomplishment in HIV research. However, HIV persists in patients despite long-term ART therapy and if ART is withdrawn, the virus almost invariably rebounds. Lifelong ART treatment is associated with toxicity, residual chronic inflammation, and the accelerated onset of diseases associated with aging. Therefore, alternatives to lifelong ART are being pursued, with the goal of achieving sustained, ART-free HIV remission. The first pathway to sustained ART-free HIV remission is to completely eradicate the replication-competent HIV reservoir–a classic “cure.” The second pathway is to control HIV rebound without eradication of the virus–referred to as “sustained virologic remission.” Three potential avenues to achieving sustained virologic remission will be discussed. The first approach involves the preservation of natural HIV-specific natural immunity without additional immune enhancements. A key challenge is to determine why the time to HIV rebound following interruption of ART has varied so widely. The second approach involves therapeutic vaccination; in this regard, the results of a recently completed, placebo-controlled therapeutic vaccine trial will be discussed. The third approach is the passive transfer of HIV-specific antibodies. Recent data on the passive transfer of broadly neutralizing anti-HIV antibodies (bNAbs) to individuals whose viremia is suppressed by ART and the effect of these bNAbs in suppressing viral rebound will be presented. In addition, the role of passive transfer of anti-α4β7 antibody in inducing long-term, post-ART remissions in non-human primates will be discussed.