Stopping Antiretrovirals After Therapy Intensification, Macrophage Stimulation and Immune Activation in HIV-Infected Adults on HAART and with HIV Viral Load Below Detection Limit

Objective
Assess whether therapeutic vaccination with Remune™ initiated after intensification of an optimal HAART will allow for long periods of HAART interruption (TI) while continuing Remune™ administration and after stopping it.

Study Design
A pilot, proof of concept, exploratory study where ten participants on HAART for more than 12 months with viral loads below detection limit (<50 copies/mL) for the last six months prior to entering study received an intensive treatment period of ddI, Hydroxyurea and GM-CSF + their current ART. The first dose of Remune™ vaccine was given at the beginning of the fifth month. All ARTs were stopped after six months if participant was clinically healthy, had viral load below detection limits and both participant and study physician felt it was safe to do so. Two months after therapy cessation, the 2nd dose of Remune™ was given. ART and Hydroxyurea were resumed if, after initial rebound, viral loads did not decrease below 50 000 copies/mL within three months or if CD4 counts decreased below 200 copies/ml. Last change to protocol extended the follow-up period to 24 months and added four Remune™ administrations.

Study Population
Ten adults with chronic HIV disease (five with previous AIDS) with viral load below 50 and a median CD4 count of 385 cell/ml were enrolled in this five-year long proof of concept trial.

Results
Participants received 11 doses of Remune™ at three-month intervals and underwent two to seven treatment interruptions. After stopping HAART, viral load rebounded in all patients after 7-28 days. Rebound decreased significantly from a median of 5.95 log (range of 4.86 to 6.74) at first TI to 5.02 log (range of 4.46 to 5.72) to last TI. The time to peak viral load increase from six (range of 2 to 11) to fourteen (range of 1.6 to 62) weeks. Duration of TI increased from a median 15 (range of 12 to 24) to 24 (range of 11 to 45) weeks. Two participants had continuous TI of three years after first and third TI respectively. TI duration was correlated with nadir CD4 and peak viral load before HAART, and to a lesser extend with IL-15 levels and magnitude of HIV-1 GAG specific responses. Increase breadth and magnitude of HIV-1-specific responses and significantly higher levels of serum IL-15 and IL-2 were documented.

Conclusions
This five-year proof of concept work provides evidence to support that chronically HIV-infected adults can be strategically managed to benefit from intermittent individualized HAART interruption.

Note: these results were taken from an abstract presented at the AIDS Vaccine 2005 International Conference, Montreal, Quebec, Canada, September 6-9, 2005 (Poster 927P).