Thanks for the information.
As far as this study on Rapid Protease Inhibitor Resistance Seen in Advanced HIV Disease: there are so many variables that will affect responses to new treatments: prior treatment, length of prior treatment, pre-existing mutations, CD4 levels, viral loads, dosing, etc. that it is hard to compare.
The patients in this study had all been treated previously with reverse transcriptase inhibitors. They were very sick, with low CD4 levels (mean=12) Some of the patients had pre-existing protease mutations, presumably from the previous rti treatment.
On the other hand, in Charles Farthing's study, COMBINING PROTEASE INHIBITORS HOLDS PROMISE, reported at ICAAC, and posted here previously, it was found that a combination of two protease inhibitor drugs suppressed levels of the AIDS virus to undetectable amounts not only in the blood of HIV-infected patients but also in their brain and spinal fluid, important reservoirs for the virus.
This study was one of the first to suggest that protease inhibitors, in particular the drugs ritonavir/saquinavir can fight the AIDS virus in the central nervous system, according to lead investigator Dr. Charles Farthing, medical director of the AIDS Healthcare Foundation in West Hollywood, Calif., and an associate clinical professor of medicine at the University of California, Los Angeles.
Triple-drug AIDS "cocktails," which regularly include one powerful protease inhibitor, have repeatedly been shown to suppress HIV to undetectable levels in patients' blood. But doctors know much less about the effects of protease inhibitors elsewhere in the body, or of two protease inhibitors used together.
In Farthing's study, 13 patients who were taking ritonavir and saquinavir and who had undetectable blood levels of HIV after 60 weeks of treatment volunteered to have a sample of cerebrospinal fluid drawn. Of them, 12 had no detectable levels of HIV in the fluid. Farthing thought that the "findings are very encouraging. They are another positive step in the fight against HIV."
He said he expects dual protease inhibitor therapy to become more common, either with two protease inhibitors alone or in quadruple drug combinations with older anti-HIV drugs like AZT and 3TC.
"Dual protease inhibitor therapy is going to be very popular in the future," said Dr. Steve Deeks, an assistant clinical professor of medicine at the University of California, San Francisco. "I believe that in 1998, dual protease inhibitor therapy will be standard."
Dr. David Ho, of the Aaron Diamond AIDS Research Center in New York and one of Farthing's collaborators, said he also expects that doctors will increasingly be prescribing protease inhibitors together.
"Dual protease inhibitors in certain studies show good results," Ho said. But he added that it is important for researchers to identify "compatible" protease inhibitors that do not cause increased side effects.
The 13 patients in Farthing's study are part of a larger ongoing study of ritonavir and saquinavir in a total of 140 patients. After completing 48 weeks of therapy, 90 percent of these patients had achieved undetectable HIV levels in their blood, according to Farthing. A small portion of the patients also took other anti-HIV drugs, but only if the HIV levels in their blood became elevated. The regimen was well-tolerated, he said, with the most common side effects being tingling around the mouth, diarrhea, fatigue and nausea.
Farthing said that dual protease inhibitor therapy appears to be most effective in patients who have never taken a drug in this class. But that's not to say that patients who have taken a protease inhibitor won't benefit from trying two of the drugs together. "I think we're going to see every conceivable mixture of AIDS drugs being tried in many different patients," he said.
Actually, Nelfinivir is being tested with DMP-266 and with Crixivan as
well. It is also being tested in combination with Ritonivir and saquivinir, and Vertex 478-141W. |
