Report 6 From Intl Geneva Conference
from Jules Levin
I just returned from the 5:30pm Abbott Symposium where they reported preliminary data from a an initial study of the double protease inhibitor regimen of ritonavir+indinavir at a dose of 400 mg/400 mg bid with d4T/3TC. In a naive treatment group 8/9 had <50 copies at week 32. I think they reported all participants in this small study were undetectable using a standard assay by week 12. Baseline CD4 was about 350 cells. The CD4 increases were about 380 above baseline. There was no food effect. Pharmacokinetics of this combination were reported and ritonavir raises indinavir trough levels and lowers its Cmax (peak blood drug level). The AUC is flattened out over the dosing period. The investigators believe the lower Cmax will eliminate or lower the indinavir kidney stone side effect and raise the trough high enough that additional potency results.
They reported several individuals who had failed indinavir received this combination and experienced 1.5 log drops in viral load without I think having changed their accompanying NRTIs. Of course durability is the key because other regimens have reduced viral load for protease failures but have not been durable. Several persons who were taking ritonavir+saquinavir and had undetectable viral load who experienced a CD4 increase were switched to indinavir+ritonavir and experienced an additional CD4 increase of 100 cells. The Abbott investigator suggests the added potency from the regimen switch may be responsible for the additional CD4 increase.
Additional studies should be conducted. I suggested some populations to Abbott researchers for study: individuals with full viral load suppression but without a CD4 increase; persons whove failed protease therapy; study of a potent regimen to maximize viral load suppression with such a regimen as RTV+IDV+NNRTI+3TC. At this Conference David Ho suggested that the latency problem may be actually a problem of ongoing replication. He suggests this because he reported that he observes the latent proviral DNA reservoir to be decaying. Others have reported here and at Resistance Meeting that viral replication may be ongoing in lymph tissue despite potent suppression in plasma. He further suggested here that a more potent regimen may address this ongoing replication situation.
Going out to dinner.