Antiretroviral Therapy With Structured Treatment Interruptions Could Benefit Those With Acute HIV Infection
People who are newly infected with HIV may benefit from highly active antiretroviral therapy regimens that involve structured treatment interruptions, although it is too soon to tell whether STI will be beneficial for people with chronic, long-term HIV infection, according to a study published in today's Journal of the American Medical Association. Dr. Franco Lori of the Research Institute for Genetic and Human Therapy in Washington, D.C., and Julianna Lisziewicz of the Policlinico San Matteo in Italy reviewed all English-language articles published in MEDLINE between January 1999 and August 2001 related to HIV treatment interruptions. They also reviewed treatment interruption-related abstracts from international conferences. STI is not part of "routine" clinical practice, but is typically characterized by several interruptions of treatment for varying periods of time. The researchers examined the impact of STI on three different types of HIV patients -- those with acute infection, those with chronic infection and those who have experienced treatment failure.
HAART with STI appeared promising for patients with acute HIV infection. A study of eight patients in Boston found that all participants achieved long-term control of HIV replication in the absence of drug treatment after one or more treatment interruptions, and only one participant developed HIV antibodies. These results indicate that there are two possible options for STI among acutely infected patients: either drug treatment can be resumed after HIV reappears in the plasma -- a strategy that would be complicated to administer -- or a fixed schedule of treatment cycles could be set, although the optimal length of treatment and interruption has yet to be determined. The second option would be "relatively easy" to administer to a large number of patients, the researchers write. However, people with chronic infection may not achieve these results because their immune systems are damaged, whereas the immune systems of acutely infected patients are still strong. The study states that it remains to be seen whether "the damage inflicted by HIV on the immune system can be reversed at any given time during the course of infection." Interrupted treatment can mobilize a chronically infected patient's T cells, but this stock of T cells is quickly depleted once control of viral replication is lost. Although STI during chronic infection could potentially "reconstitut[e]" the immune system, this outcome "remains questionable for any given patient," the study states. In patients who have experienced treatment failure, STI could prompt "a change in the most prevalent viral quasi species from multidrug-resistant to wild type, potentially improving sensitivity to subsequent salvage therapy regimens," the authors state. However, the use of STI in patients experiencing treatment failure "has not been met with great success," and it is unknown whether changing the length of treatment cycles could alter patient outcomes.
"At present, STI may be most beneficial for patients treated with HAART during the acute phase of infection, as they are most likely to be able to develop enhanced immune responses," the authors conclude. Future research goals should include improving the ability to determine immune competence in chronically infected patients and developing tests that can predict which patients are the best candidates for STI. Other strategies, such as adjusting the length of treatment cycles, initiating adjunct therapies and administering a combination of an HIV vaccine and STI, could also prove beneficial. "However, it is too early to recommend the routine use of STI in any clinical setting because the end result remains unpredictable, and the potential hazards to patients have not yet been properly evaluated," the authors conclude (Lori/Lisziewicz, JAMA, 12/19).