Treatment interruption strategies

Once it became clear that treatment interruptions to stimulate immune response or encourage reversion to drug-sensitive virus offered little benefit, researchers turned their attention to treatment breaks aimed at lessening treatment fatigue and reducing long-term toxicities.

Some of the earliest treatment interruption studies stopped and restarted therapy according to a schedule of fixed-length cycles, without regard to CD4 cell count. Results from fixed-cycle treatment interruption studies have been mixed, showing little clear clinical benefit. However, some approaches, such as five days on, two days off, do seem to be preferred by patients, and others may reduce side-effects.

Since HIV disease progression typically occurs when the CD4 cell count declines below a certain level, the other frequently studied approach involves stopping and restarting therapy at specific CD4 cell thresholds. Although early results suggested that this approach might be beneficial in terms of minimising total exposure to drugs, recent findings have shown that it can make patients more vulnerable to morbidity.

Unlike treatment interruption prior to salvage therapy, where people had advanced HIV disease, a low CD4 cell count, a high viral load and often a history of past opportunistic illness, studies of treatment breaks to reduce side-effects and improve quality of life have focused more on ensuring patient safety. Such studies generally include only participants with a high CD4 cell count (often well above 500 cells/mm³) and sustained viral suppression.

Additional therapies have been tried in combination with structured treatment interruptions, with the aim of lengthening the time a person can remain off therapy. These have included therapeutic vaccines, interleukin-2 (IL-2), prednisolone and hydroxycarbamide.

The pilot ACTG 5102 study, which assessed the use of IL-2 in combination with antiretroviral therapy to boost the CD4 cell count before stopping therapy, found that most patients maintained a higher CD4 cell count while undergoing a treatment interruption of 48 weeks.¹ Some of these approaches have yielded promising results in preliminary trials, but given recent shifts in the overall approach to effective antiretroviral therapy, such strategies have generally fallen out of favour.