Being Alive 1997 Nov 5: 6
Adding the recently approved non-nucleoside reverse
transcriptase inhibitor delavirdine to the multidrug regimen of
HIV-infected patients experiencing "failure" of protease
inhibitors can produce a "remarkable" decrease in viral load
and significant clinical improvement. The effect is most
pronounced, Dr. Paul Bellman said, when the regimen includes
the protease inhibitor indinavir.
"This therapy has reproduced the magic of protease inhibitors
for some of the patients for whom protease inhibitors have not
worked," he said.
Dr. Bellman, of St. Vincent's Hospital, New York, entered 46 of
his patients for whom antiretroviral therapy was not working
into Pharmacia and Upjohn's expanded access program for
delavirdine (Rescriptor). "This represents a group of patients
who are extremely treatment experienced," Dr. Bellman said,
"including all of the available protease inhibitors." He
noticed very early that some of the patients "were getting
really extraordinary benefits."
During follow-up, there was a rapid decrease in HIV RNA. "But
that obscures the fact that actually a fair number of patients
have gone to 'undetectable'," Dr. Bellman noted. While some
patients responded minimally or not at all, 12 of the 46
patients have maintained viral levels below the detection
threshold for 6 to 10 months.
The efficacy of delavirdine in this setting exceeds
expectations based on its intrinsic virologic potency, which Dr
Bellman attributes to its synergistic effect with indinavir.
Notably, nearly all the patients in the group of complete
responders had been on indinavir in combination therapy, had
initially responded but had lost viral suppression. The
addition of delavirdine "increases indinavir levels,
particularly trough levels" by inhibiting the p450 enzyme
system in the liver that metabolizes indinavir. Hence, drug
levels are increased sufficiently to allow any partial
resistance to indinavir to be overcome.
"I believe that indinavir and delavirdine in combination
therapy is, at this particular point, the best demonstrated
salvage therapy for protease-experienced patients who are
breaking through virologically," Dr. Bellman stated. "In my
mind, it often has a better response than changing indinavir to
ritonavir and saquinavir, or any other combination that has
been studied," he added.
Reprinted from We The People with HIV/AIDS of the Delaware