Islatravir-Based HIV Treatment Regimen Fails

[Jim Allen]

Interesting update, we have to see how stage 3 turns out of course.

Poz.com write-up in full: https://www.poz.com/article/islatravir-plus-pifeltro-shows-promise-2drug-hiv-regimen

In short:

Islatravir Plus Pifeltro Shows Promise as 2-Drug HIV Regimen
A mid-stage trial showed the combo suppressed HIV, was well tolerated and resulted in a low rate of virologic failure.

The randomized, double-blind trial enrolled 121 people with HIV who had not previously taken treatment for the virus and had no known resistance to ARVs.

The study had two parts. In part one, the participants were randomized to receive islatravir at either 0.25 milligrams, 0.75 mg or 2.25 mg plus 100 mg of Pifeltro and 300 mg of lamivudine or to receive Delstrigo. Twenty-four weeks later, in part two, those who received islatravir and who had an undetectable viral load (below 50) stopped taking lamivudine and kept taking the remaining two-drug regimen of islatravir plus Pifeltro for another 24 weeks.

Findings presented at the 2019 International AIDS Society Conference on HIV Science in Mexico City indicated that 90% of those who took 0.75 mg of islatravir—the dose that will continue on to Phase III trials—had a fully suppressed viral load at the trial’s 48-week mark, compared with 84% of those on the three-drug regimen. These rates were considered comparable.

[Jim Allen]

To be honest, it doesn't seem like terrible results at 48 & 96 weeks if you ask me. The PLHIV were treatment native and I think it's fair to say they tend to have VL blips with any treatment more frequent at first. Although, it's a small sample size.

In full POZ.com writeup:
https://www.poz.com/article/islatravirbased-hiv-regimen-fails-study-participants

in Short:

The study enrolled 121 people with HIV, randomized initially to received islatravir at either 0.25 milligrams, 0.75 mg or 2.25 mg daily plus Pifeltro (doravirine) and lamivudine daily; or they received a fixed-dose combination of Delstrigo (doravirine/tenofovir disoproxil fumarate/lamivudine). The study was set to run for 96 weeks.

Those in the islatravir groups who had a fully suppressed viral load (less than 50) 20 weeks into the study or later were taken off lamivudine at their next clinic visit.

Orkin and her colleagues defined virologic failure as having a viral load of 50 or greater after having achieved full viral suppression at any time during the study, called a rebound. Or this outcome was defined as not achieving a viral load below 50 by week 48 of the study, called a nonresponse.

At week 96 of the study, 86.2% (25 of 29) of those who received 0.25 mg of islatravir had a fully suppressed viral load, as did a respective 90.0% (27 of 30) and 67.7% (21 of 31) of those who received 0.75 mg and 2.25 mg the drug. By comparison, 80.6% (25 of 31) of those who received Delstrigo had a viral load below 50.

During the first 48 weeks of the trial, six participants discontinued treatment due to virologic failure. This included two rebounders each in the 0.25 mg and 0.75 mg of islatravir groups, one nonresponder in the 2.25 mg group and one rebounder in the Delstrigo group.

Following the 48-week mark, one additional participant discontinued treatment due to virologic failure. This person, who was in the 2.25 mg group, saw their virus rebound to 70 at the 72-week point.

All those who experienced virologic failure had a viral load between 50 and 79. This meant that none had a viral load high enough to conduct resistance testing on their virus.

After the seven people who discontinued treatment switched to new HIV regimens, three—one each from the 0.25 mg and 0.75 mg groups and one from the Delstrigo group—continued to have a viral load that was above 50 and yet remained low.