Patients treated at a time after primary HIV infection, and who have undetectable viral loads.

Patients treated at a time after primary HIV infection, and who have undetectable viral loads.

Rationale # 1: To stop therapy in patients that started treatment when the numbers of CD4 cells were high and viral loads were low. The numbers of CD4 cells reflect the status of the body's immune system. Thus, the higher the number of CD4 cells, the stronger is the immune system, and the lower the number, the weaker (more suppressed) is the immune system. I discussed this issue in some detail in my March Doctors Column.

Briefly, new guidelines have supported the possibility of delaying the start of therapy until CD4 cells are less than 350, or if higher, when the viral load is greater than 30-65,000 copies/ml. Remember that these are only guidelines, and should not replace the judgment of individual patients and their physicians. Nevertheless, this new approach has led many people to reconsider the need to stay on therapy.

At the current time, however, limited data are available to provide guidance to patients and doctors in this situation. Most experts would agree that if the person is doing well on therapy with good tolerance of the drug and adherence to the regimen, it is probably best to continue treatment until more information becomes available. On the other hand, if tolerance is poor, or there are concerns regarding adherence, serious consideration should be given to a change in therapy, including the possibility of discontinuing treatment with close follow-up.

Rationale # 2: To boost immune responses to HIV in order to enhance viral control when off antiretroviral therapy. In this situation, several studies have shown that immune responses can actually be enhanced when therapy is stopped and viral rebound occurs. Evidence showing that this enhanced immune response is associated with improved virologic control, however, is not very encouraging. Accordingly, most researchers agree that this approach remains experimental. As a matter of fact, generally little optimism exists that it will result in clinically relevant benefits for patients. In addition, the paramount concern remains that stopping and then re-starting therapy can result in the development of drug resistance.

Rationale # 3: The goal is not to discontinue (stop) treatment, but cycle (interrupt and restart) it so that the actual time on therapy can be decreased. This concept currently is being explored in small studies where treatment is started and stopped at weekly or monthly intervals. The amount of experience with this approach, however, is extremely limited. While there are always concerns regarding the development of resistant virus when therapy is discontinued, it is particularly worrisome in this setting. Most experts, therefore, would agree that this is not a strategy to consider in clinical practice until more research is completed.