Structured treatment interruptions in HIV infection: benefit or disappointment?

Many investigators are and have been studying the impact of structured treatment interruptions in HIV patients on subsequent viral control, HIV-specific cellular and humoral immunity, improvement of quality of life, and reduction of side effects and costs. Although varying treatment schedules have been followed and few clinical trials of different cohort size have been completed, tentative conclusions can already be drawn. Firstly after the initiation of treatment during acute infection followed by structured treatment interruptions, some patients maintained low level viremia during many months, such control of viremia has not been observed after the initiation of treatment during chronic infection followed by structured treatment interruptions. Second, structured treatment interruptions lead to an increase in frequencies of HIV-specific CD8(+) T-cell populations, however, these frequencies are not above pretreatment frequencies in chronically infected patients. Third, HIV-specific CD4(+) T-cell responses can be induced or enhanced during structured treatment interruptions but this augmentation was usually only transient. Finally, selection of drug-resistant virus variants may occur during structured treatment interruptions but clinical resistance to treatment has been quite rare. The initial hopes that structured treatment interruptions would substantially enhance immune control in the absence of therapy have not been confirmed, particularly in patients who initiated therapy during chronic infection. Additional immune-stimulatory interventions are now being considered and tested, such as administration of cytokines or vaccination. Furthermore, the demonstration of reduced side effects or costs due to structured treatment interruptions awaits the completion of large, comparative studies with a follow-up of several years.