GLASGOW, United Kingdom — Viral suppression was induced in heavily pretreated patients with HIV after they received the investigational drug fostemsavir (ViiV Healthcare) for 24 weeks along with their regular regimen, extended results of the BRIGHTE trial show.
“We’re seeing these patients becoming virally supressed much later than what we see in a trial with more treatment-naïve patients,” said Peter Ackerman, MD, PhD, from ViiV Healthcare.
“And I can tell you that we”re still seeing that beyond week 48,” he told Medscape Medical News
Heavily pretreated patients are among the hardest people to help. Most have been HIV positive for a very long time and have developed resistance not only to drugs but sometimes also to whole classes of drugs, such as non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and more.
As options dwindle, the virus gains the upper hand. In the BRIGHTE trial, 86% of participants had a history of AIDS-defining illnesses. Several had CD4 counts <20.
“These are very sick patients,” said Ackerman, who presented the week 48 BRIGHTE data here at HIV Drug Therapy 2018. “This is a treater population and a patient population where there have historically been relative wins — preserving CD4 count or getting viral load reduced by half a log or a log.”
These are also patients who are often excluded from trials of other drugs because of their high viral loads or their low CD4 counts. When they are included, they are usually the cohort of patients for whom new drugs perform worst.These are very sick patients.Dr Peter Ackerman
These are exactly the people who were enrolled in the BRIGHTE trial. Nearly half of the people screened for the trial — 360 of 731 — were not included in the trial. Many of them, said Ackerman, had not yet experienced treatment failure with enough drug classes to qualify for the study. To join, people had to have experienced treatment failure on every drug available in four of the six antiretroviral drug classes.
Ackerman presented data for two studies of fostemsavir: 48-week results from the randomized BRIGHTE trial of 272 participants and from a nonrandomized trial of 99 of the “sickest of the sick.” The latter study was “almost a compassionate use study” because it was for people for whom no other drugs worked, he said. Twelve of the people in that study had died by week 48, but none had died because of the study drug.
At week 24, 54% of patients achieved viral load suppression, as previously reported by Medscape Medical News. At week 48, 54% were also virally suppressed. But they were not all the same participants. Some participants had left the trial before week 48, either because the drug had not been effective for them, they had experienced adverse events, become pregnant, were lost to follow-up, or had died, Ackerman explained.
The patients who often do not do well in other studies — older patients, black patients, and female patients — reached viral suppression at statistically the same rate as other participants. In that group, rates of viral suppression were even slightly higher.
It’s a phenomenon they don’t totally understand, said Ackerman, but the researchers are hoping that “week 96 data may shed better light on it.”
In addition to a long, slow decrease in viral load, the research team saw something else: as the weeks went on, even for patients who continued to have detectable viremia, CD4 counts began to rise.
“Patients with baseline CD4 counts of <20 cells/mL had an increase of nearly 150 cells/mL by week 48,” said Ackerman. “That was equal to those who had a baseline CD4 of ≥200 cells/mL. That’s life changing for these people in terms of morbidity and mortality.”
The results were greeted with hope by audience members.
Hope and Choices
“Thank you, Peter,” said one audience member. “We are really looking forward to the drug,” adding that he wanted fostemsavir to be used with ibalizumab (Trogarzo, Teratechnologies Inc), the first monoclonal antibody for HIV.
Nadia Ahmed, MD, of the Desmond Tutu HIV Center, Cape Town, South Africa, works primarily with adolescents — quite different from the patient population in the fostemsavir studies, which had a mean age of 49 years. But her patients also are often heavily pretreated and in need of new treatment options.
Although fostemsavir needs to be taken twice a day, she called it a “promising” development.
“The data are good, but also it comes down to patient choice,” she said. “Whether it’s once a day or twice a day or thrice a day, you need to present the patient with all of the data — efficacy, tolerability, safety, give them the whole picture — and then let them make the decision.”
The presentation of the BRIGHTE results was just one of a handful of presentations that showed promise for clinicians who care for people with treatment-resistant HIV. In addition to fostemsavir, researchers presented new data from ibalizumab, which demonstrated continued viral suppression for pretreated patients. And data on the entry inhibitor MK-8591 (previously known as EFdA) showed improved efficacy against HIV already resistant to nucleoside reverse transcriptase inhibitors.
All of these findings, along with the development of long-acting injectible cabotegravir/rilpivirine and a robust pipeline of drugs for both treatment-naive patients and long-acting agents, led Alexandra Calmy, MD, of the University of Geneva, to say that “2018 has been an important year for HIV research.”
“There is a rich pipeline for patients harboring multidrug-resistant viruses,” he said.
For Roy Gulick, MD, of Weill Cornell Medical Center in New York City, the data on drugs that target novel places in the HIV lifecycle point to a future in which patients generally take fewer pills a day — MK-8591 is administered as an infusion every other week, he pointed out.
“These brand new drugs with brand new mechanisms of action offer hope” for heavily pretreated patients, he added.
BRIGHTE was funded by ViiV Healthcare. Dr Ackerman is an employee of ViiV Healthcare. Dr Gulick and Dr Ahmed have disclosed no relevant financial relationships.
HIV Drug Treatment 2018. Abstract O344A, presented Oct. 31, 2018.