To cure chronic HIV infection, a new therapeutic strategy is needed

With the advent of highly active anti-retroviral therapy (HAART) in 1997, most investigators felt that HIV infection would be cured with a few years of antiviral therapy. It is now clear that antiviral drugs alone cannot cure the infection, even when applied within a few weeks of initial symptoms. There are now several reports of the discontinuation of HAART after several years of effective suppression of detectable plasma virus. Relapse occurs universally within a few weeks. More promising results have been reported if HAART is initiated early after infection. However, even in this instance, most patients suffer a relapse within a few weeks. If diagnostic treatment interruptions are performed, some individuals appear to control plasma virus concentrations at low levels - <5000 HIV RNA molecules/ml. We have similar results from subjects who were infected chronically before HAART was initiated, so that it is clear that the previous dogma that HIV-specific immune reactivity is absent in individuals who are chronically infected is incorrect. Immune reactivity to HIV does exist, and is detectable in vivo, even when the infection becomes chronic before therapy is initiated. Consequently, we are now faced with a new therapeutic dilemma: how can a cure of this infection be achieved? This review is focused on the rationale and methods to design clinical trials directed towards achieving a cure of HIV infection.