Structured treatment interruptions as a potential alternative therapeutic regimen for HIV-infected patients: a review of recent clinical data and future prospects

Highly active antiretroviral therapy (HAART) allows for substantial control of HIV replication in vivo, and has caused a significant decline in morbidity and mortality rates among patients. However, eradication of the virus from the body is not possible. Therefore, HAART necessarily becomes a life-long treatment and this is associated with several problems: (i) the high cost of therapy; (ii) increased frequency of drug-related side effects; (iii) viral resistance; and (iv) poor patient adherence to the treatment. Based on these considerations, among other alternative strategies, structured treatment interruptions (STI) have been proposed with the potential object-ive of inducing immune-mediated control of HIV replication in HIV-infected patients. The available clinical data indicate that STI might increase HIV-specific, cell-mediated immune responses in patients treated during primary HIV infection; however, it does not seem to have the same effect in patients treated during chronic infection. Nevertheless, in chronically infected patients STI might limit drug-related side effects by decreasing exposure to drugs, without influencing the efficacy of the therapy. In addition, recent data suggest a possible role for immune-modulations such as hydroxyurea and therapeutic vaccines as adjuvant therapies for limiting viral rebound in these patients. Preliminary indications suggest that there is reduced hope for STI as a salvage therapy. Finally, it is important to stress that no controlled, randomized studies of STI have been held in humans, and it is not possible to evaluate fully the clinical impact of such a strategy. Therefore, clinicians and patients should avoid using STI outside the setting of controlled clinical trials.