The data from a phase I/II study showed significant reductions in viral load among HIV-positive patients receiving GS 9137, or JTK-303, a novel oral HIV integrase inhibitor, as monotherapy or in combination with ritonavir as a boosting agent, compared to placebo.
Integrase inhibitors are a new class of antiretrovirals that interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells. Novel classes of HIV-fighting drugs are needed as patients live longer and exhaust currently available treatment options.
" Ten years after the introduction of combination therapy for HIV, we are seeing an increase in the number of patients whose virus has developed resistance to many of today's drugs," said DeJesus, the study's principal investigator. " New and better options are desperately needed, particularly among treatment-experienced patients who must often take complex regimens."
This Phase I/II study was a double-blind, randomized, placebo-controlled monotherapy study to evaluate the safety, tolerability and antiviral activity of GS 9137 in HIV-infected treatment-naive and treatment-experienced patients.
Forty patients were randomized and received one of five doses of GS 9137 ( n=30 ) or placebo ( n=10 ) with food for 10 days.
The study evaluated GS 9137 at 200 mg twice daily ( BID ) ( n=6 ), 400 mg BID ( n=6 ), 800 mg BID ( n=6 ), 800 mg once daily ( QD ) ( n=6 ), and 50 mg boosted with 100 mg Ritonavir QD ( n=6 ).
At study entry, patients were not receiving antiretroviral therapy, had HIV RNA ( viral load ) between 10,000 and 300,000 copies/mL and CD4 cell count greater than or equal to 200 cells/microliter.
At baseline, study participants had a mean viral load of 4.75 log10 copies/mL and mean CD4 cell count of 442 cells/microliter.
The primary efficacy endpoint was the maximum reduction in viral load from baseline.
GS 9137 monotherapy demonstrated significant antiviral activity compared to placebo ( p < 0.0001 ) at all doses.
There were no discontinuations or serious adverse events in groups receiving GS 9137.
All adverse events were grade 1/2 in severity, resolved while on treatment and were not associated with GS 9137 dosing.
Source: Gilead Sciences, 2006