Experimental Drug Offers HIV Control For Some When Standard Therapy Fails

The experimental drug can lower the HIV-1 virus level in patients resistant to conventional therapy, according to a new study that looked at 371 volunteers for whom established drugs were not working.
After 8 days of therapy, the decrease in the viral load among fostemsavir recipients was 4.6 times greater than it was for patients who received placebo (P<0.001).
At week 48, 57% of fostemsavir patients had an HIV-1 RNA below 40 copies per ml of blood vs 45% with placebo therapy.
"And remember, they only had placebo for 8 days, then they got the study drug," coauthor Dr. Michael Kozal, professor of medicine at Yale School of Medicine told Reuters Health in a telephone interview.
In a group that was not randomized because they had run out of treatment options and received the drug on an open-label basis, 38% attained a viral load level below 40.
Seven percent of fostemsavir patients discontinued the drug because of side effects, mostly due to infection.
"For people who don't have other treatment options, this is a new drug class and this is very important. We need new therapies for people who have exhausted all their other regimens," said Dr. Kozal, who is also chief of staff at the VA Connecticut Healthcare System.
The results appear in The New England Journal of Medicine. Bristol-Myers Squibb and GSK/ViiV Healthcare paid for the study, known as BRIGHTE. The trial is ongoing.
Fostemsavir works by preventing the HIV virus from attaching to host T cells and other immune cells.
All of the volunteers had HIV-1 RNA counts of 400 copies per ml or above at the start of the trial, and they had exhausted at least four of the six classes of antiretroviral drugs. Overall, 83% had tried at least five antiretroviral regimens before entering the study.
In the group of 272 who were initially given fostemsavir or placebo, the blinded treatment lasted 8 days, after which all were able to take the drug. The remaining 99, for whom there were no fully active, approved antiretroviral drugs, simply received fostemsavir in addition to optimized background therapy.
The withdrawal rate was high: 21% in the randomized group and 32% among nonrandomized patients. The most common reasons were death (20 patients), therapy failure (18 patients), protocol violation (16 patients) and adverse events (14 patients).
The response rates were best among patients over age 49 (59%), females (61%), blacks (65%) and those who still had at least one antiretroviral drug that was working for them.
Despite the dropout rate, the researchers reported that "the frequencies of adverse events and serious adverse events were similar in the two groups."
"Most serious adverse events were due to infections or complications associated with advanced AIDS," the team reported.
"Remember, these are extremely advanced AIDS patients and many have events related to their other drugs," said Dr. Kozal.
If approved by the US Food and Drug Administration, the drug "would probably be something we would reserve for patients who really don't have options. And if they can't tolerate a drug for another reason, we would use it in those cases," said Dr. Emily Blodget, an associate professor of clinical medicine at the University of Southern California Keck School of Medicine, who was not involved in the study.
She estimated at 15% to 20% of patients in her clinic have some drug resistance.
"If you're compliant with your medication, the current medication is pretty successful," she told Reuters Health in a telephone interview. "But we're always looking for novel treatments, particularly because we have people who are still not compliant with their regimen."
BRIGHTE was done at 108 sites in 23 countries.
—Gene Emery
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