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.

Investigators have also proposed other goals for the interruption of treatment. For example, the suggestion has been made that patients who have developed resistance to their antiretroviral therapy may be able to stop the therapy to allow the resistant virus to "go away." Then, a new drug regimen can be started with enhanced viral suppression. Finally, others have proposed serial interruptions of therapy to minimize the amount of time people are actually taking their medications. The hope here is that the diminished time on the drugs will result in less toxicity for the patient.

So, the goals of interrupting therapy in these different situations differ. Yet, despite these important differences, each of these strategies has been described in a similar way, as "strategic, structured, or scheduled" treatment interruptions, often abbreviated as STI. The problem is that this one term, STI, has been used loosely to describe various situations. As a result, this use of the term STI has led to considerable confusion among patients and their doctors.

Consequently, it is vital that people understand certain key aspects of each of these different strategies. For instance, for each situation, people need to know the circumstances under which STI is being explored, the data supporting the use of STI, and the potential risks of STI. Below, I have outlined the situations in which interruption of treatment, or STI, is currently being considered. 

1. Patients treated during the primary HIV infection, and who have undetectable viral loads.

This situation is unique to the relatively rare individuals that are diagnosed with HIV, and treated during the first weeks or months of the primary (initial) infection. The time of treatment does not refer to the time from when the HIV was first diagnosed by an antibody test. Rather, it refers to the time from when the transmission (spread and acquisition) of HIV actually occurred. In this situation, early treatment that results in undetectable viral loads is believed to preserve the natural immune response to HIV. Also, allowing the viral load to rebound (bounce back) after stopping treatment, should stimulate the immune system to control the HIV. What's more, subsequent interruption(s) of treatment, should ultimately allow the discontinuation of therapy.