Structured treatment interruptions involving cycles of a four week break from anti-HIV therapy followed by eight weeks of HAART do not boost the immune system, reduce side-effects or suppress viral load, according to an investigation published in the August 1st edition of the Journal of Infectious Diseases, which is now available online. Indeed, investigators had to terminate their study early for safety reasons after several patients developed drug resistant HIV as a consequence of taking treating breaks.
It was hoped to enroll 90 patients with chronic HIV infection to the study. A total of 52 patients were recruited before the study was terminated on the grounds of safety. Of these 26 were randomly assigned to receive long cycle structured treatment interruptions involving four weeks without HAART followed by eight weeks anti-HIV therapy. The other 26 patients received continuous HAART. The primary end point of the study was intended to be the proportion of patients with an HIV viral load below 50 copies/mL after 48 weeks. Secondary end points included CD4 cell count, HIV specific CD4 response, levels of serum lipids and liver function.
The study was terminated prematurely after new resistance mutations were detected in three patients receiving efavirenz based regimens. However, 46 patients had by this time completed the 48 weeks of the study, 19 in the treatment interruption arm and 22 in the continuous HAART arm. Investigators analysed data from these patients. All the patients had had a viral load below 500 copies/mL for at least six months prior to enrollment in the study, and below 50 copies/mL in the study’s screening period immediately before the study commenced. None had any drug resistant HIV, and at baseline all the patients had a CD4 cell count above 300 cells/mm3.
At baseline, and after the 48 weeks of the study, there were no significant differences in serum lipids, in liver function, in CD4 cell count, or in HIV-specific CD4 responses between the intermittent therapy and continuous HAART arms of the investigation. There were transient reductions in lipid levels in the patients in the interruption arm, but these returned to baseline levels by week 48.
There were no significant differences between the two arms’ HIV viral load at baseline and 48 weeks.
The investigators conclude, “the present study demonstrates that long intermittent therapy with HAART does not result in diminution of toxicities associated with HAART, nor does it enhance or decrease measurable immune parameters. In addition, long-cycle intermittent therapy that results in rebound in plasma viremia during the without-HAART periods had a significant effect on the control of plasma viremia, which suggests that clinically significant autoimmunization against…virus does not occur in this setting.”
Further information on this website
Structured treatment interruptions - overview
Treatment interruptions - factsheet
Dybul M et al. Long cycle structured intermittent versus continuous highly active antiretroviral therapy for the treatment of chronic infection with human immunodeficiency virus: effects on drug toxicity and on immunological and virologic parameters. JID 188 (online edition), 2003.