Structured Antiretroviral Therapy Interruption as a form of Immune-based Therapy in HIV-1 Infection

Recently, a huge interest on structured therapy interruption (STI) has emerged in the HIV field. STI is based on the concept of boosting HIV-1 specific immune responses with a kind of autologous vaccination by cycling antiretroviral drug interruptions in subjects who respond to antiretroviral therapy. Since the concept of HIV-1 eradication is no longer tenable, the enhancement of HIV-1 specific immune responses in order to keep viremia at low levels for prolonged periods has become an urgent treatment goal. However, there is no current effective therapeutic vaccine to boost HIV specific immune responses. Efforts to stop treatment have failed so far. Rapid rebound of plasma viral load has been reported after variable periods of successful HAART in subjects with acute or chronic HIV-1 infection. On the other hand, sporadic reports have identified subjects who were able to control virus replication after discontinuation of HAART initiated during primary infection. Fifteen abstracts from the Seventh Retrovirus Conference held in San Francisco in February 2000 described data from STI in different HIV-infected populations. All these studies try to answer the question about the possibility of inducing an HIV-1 specific immune response during primary HIV infection (PHI) or chronic HIV infection (CHI), and whether STI may be effective as an immune-based therapy. Data accumulated suggest that it might be possible to induce specific helper and CTL responses in HIV-1 infection, both in PHI and CHI. The responses obtained during PHI seem to be stronger, and the helper responses were maintained during the periods on HAART, which are of benefit for increasing and maintain CTL responses during the periods off therapy. The responses obtained during CHI are weaker, but do exist. The main problem is that both CTL and helper responses diminished during the periods on therapy. However, these findings may open a new approach for the treatment of CHI. If the immune system is able to learn how to fight effectively against HIV-1 infection it might be possible to develop therapeutic vaccines in order to improve the control of HIV-1 infection obtained during HAART.