To Interrupt Treatment or Not - That is the Question

In 1995, the availability of potent antiretroviral therapy changed the management of HIV infection forever. At that time, "drug cocktails" of medications became the standard of care, with the ultimate goal being long-term viral suppression. The subsequent years brought the realization, however, that long-term antiretroviral therapy also had its limitations, such as the development of drug resistance and toxicity. Nevertheless, simultaneously, major advances were being made in the understanding of HIV immunology.

For example, studies demonstrated that during the first months of infection, the body ordinarily mounts an immune (defensive) response to the virus. This response results in variable levels of viral control. Yet, notably, in rare cases, without therapy, the immune system is able to suppress the viral load to very low levels for prolonged periods of time. These fortunate, albeit rare, individuals have been referred to as long-term nonprogressors. On the other hand, when the virus is suppressed by antiretroviral therapy, the body's natural immunity is not stimulated by the presence of virus in the blood, and thus, the immunity declines.

This important immunologic data provided a scientific rationale for considering interruption of antiretroviral therapy. The idea of interrupting treatment is to allow the viral load to increase and thereby, stimulate the body's immune response to the virus. In other words, the virus already in the body stimulates the body's immune response in a reaction referred to as "autoimmunization." (You see, "auto" means self.) With a regular immunization, in contrast, the virus, previously rendered harmless, is injected into the body to generate the immune response. Accordingly, the goal of this strategy of autoimmunization is to allow the immune system itself to control viral replication (reproduction) after therapy was interrupted.