New HIV drugs with a higher resistance risk should be classed as inferior

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Jim Allen:
NOTE:
I am adding a note to this thread, given the direction of the conversation. Please keep in mind this is just us speaking our thoughts and fears, irrational or not, freely as PLHIV.

There were some treatment failures in the studies and clinical follow-ups under dual therapy. (Links in the thread) Still, given the numbers, it statistically seems to be relatively rare, so there is no need to panic if you are reading this thread and on dual therapy or considering it.

Just watch your adherence levels as always and talk to your doctor if you are concerned for reassurance next time you are due.

Original post:

I felt these things were known and relatively obvious, although I suppose not everyone reads drug studies in full and consults their doctors on potential risks & drawbacks.

https://www.aidsmap.com/news/dec-2023/new-hiv-drugs-should-be-classed-inferior-if-they-carry-higher-risk-resistance

--- Quote ---New antiretroviral regimens should be considered inferior to older ones unless trials can demonstrate that their failure doesn’t lead to more drug resistance than standard treatment, Italian researchers argue in Lancet HIV.

Italian physicians Diego Ripamonti and Mauricio Zazzi draw attention to the concerning resistance patterns that emerged in people who switched treatment and experienced viral rebound in several studies in which rilpivirine was combined with an integrase inhibitor.

In the SWORD studies of switching from three-drug treatment to dolutegravir and rilpivirine, 11 people experienced virological rebound. Six people who switched to dolutegravir and rilpivirine developed resistance to rilpivirine. No one who experienced viral rebound on three-drug treatment developed major resistance mutations.

In the LATTE study, participants received oral cabotegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks before switching to oral cabotegravir and rilpivirine if they suppressed viral load. Eight people experienced viral rebound and six developed drug resistance, including three cases of integrase inhibitor resistance. Again, no one who experienced viral rebound on the three-drug regimen developed resistance.

The ATLAS-2M study evaluated monthly or two-monthly injections of cabotegravir and rilpivirine in virally suppressed people who had either been taking three-drug treatment or monthly injections of cabotegravir and rilpivirine. Although the numbers were low, more people in the two-monthly injections group experienced virological failure (approximately one in forty) than in the monthly injections group (one in two hundred). Ten participants developed resistance to cabotegravir and eight to rilpivirine.

“Given the current availability of oral high genetic barrier regimens, we believe the rate of treatment-emergent resistance should be incorporated in an updated definition of HIV therapy success,” say the Italian physicians.

“Modern treatment options should be ranked according to the risk of failure with resistance [… and] patients should be informed about the potential (although minimal) risk of resistance to integrase inhibitors.”

They note that British HIV Association guidelines recommend that people with HIV who are considering a switch to injectable cabotegravir and rilpivirine should be informed about the risk of resistance to both drugs.
--- End quote ---

leatherman:

--- Quote from: Jim Allen on December 27, 2023, 06:31:18 am ---I felt these things were known and relatively obvious

--- End quote ---
two-drug regimens might not be as "effective" as three-drug regimens? Who would've thunk it? :)

kentfrat1783:
I rember when I was going to Cleveland Clinic and they stated that it would not be good to go a two pill regiment. I never asked but I was thinking there had to be a good reason for the three pill regiment and it works for me.

Unless I have an issue or my insurance says I need to change I don't see a reason to change. My main fear is resistance issues.

But on a personal opinion, I think too many poeple change just becuase they see it on TV and want the "new" pill. They need to remember it isn't a new phone or a new pair of glasses.

leatherman:

--- Quote from: kentfrat1783 on December 27, 2023, 07:38:28 pm ---I never asked but I was thinking there had to be a good reason for the three pill regiment and it works for me.

--- End quote ---
there are several steps in how HIV infects a tcell. HIV meds were developed to stop this process. Some meds stop HIV from attaching to the tcell; some stop HIV from fusing into the cell. Other meds stop HIV from integrating into the cell or inhibit the reverse transcriptase inside the cell. Other meds stop HIV from using the tcells as mini HIV factories.

What science learned was that HIV was a tricky virus. Stopping one action of the infection wouldn't stop the other ways and often let HIV learn how to adapt to the med. (that was the late 80s) Two meds seemed to work better but resistance issues eventually won out. (the early 90s) Continuing to develop all the types of meds, finally allowed HIV to be controlled when three methods of it's replication were interrupted or disallowed. (HAART was developed in the mid 90s). And that's why most anti-HIV medication regimens contain a combination of 3 meds either as separate meds or a combination medication.

Jim Allen:

--- Quote from: leatherman on December 27, 2023, 10:30:19 am ---two-drug regimens might not be as "effective" as three-drug regimens? Who would've thunk it? :)

--- End quote ---

;D lol.

--- Quote ---Stopping one action of the infection wouldn't stop the other ways and often let HIV learn how to adapt to the med. (that was the late 80s) Two meds seemed to work better but resistance issues eventually won out. (the early 90s) Continuing to develop all the types of meds, finally allowed HIV to be controlled when three methods of it's replication were interrupted or disallowed. (HAART was developed in the mid 90s). And that's why most anti-HIV medication regimens contain a combination of 3 meds either as separate meds or a combination medication.
--- End quote ---

Yeah, this isn't new. The results today with dual therapy are better than previous attempts, as the meds are far better. Resistance levels are higher, and bioavailability is better. The same goes for monotherapy. However, monotherapy is still a total shitshow.

I do have a theory, not related to the meds themselves but our behaviour/habits that could be partly to blame, although it's just a theory, no facts, just thinking out loud.

In the real world, some people take their meds only four or five days a week (3) and plenty of us take them every day but not necessarily at the same time. Thankfully, most HIV treatment combinations from 2000 to 2020 are very forgiving. The old 95% gold standard rule from the 1990s went out of the window somewhat, and I've even heard doctors saying take the meds once a day, and the when isn't that important. 1)

With Dual therapy (2) I suspect some of the issues seen are because of these habits that have crept in over the years, and a more strict level of adherence might generally be needed, like back in the late 90s, with the 95% rule. Again, this is just me thinking out loud; no evidence to confirm that it's a potential cause.

I have no idea what the story is with injectables. It could be just less of a barrier, plain inferior without user error, but I will say it's not news; I still think it's a good alternative option for people who need it or have barriers to daily ART.

1)
https://forums.poz.com/index.php?topic=73003.0
Newer HIV Regimens May Require Less Strict Adherence (Meds used in 2014-2016)

2)
https://forums.poz.com/index.php?topic=77539.0
(Monotherapy & Dual therapy) Dolutegravir resistance is rare, but some risk factors can up the odds.

3)
Caution over French study only taking ART 4 days a week
http://i-base.info/htb/36517

FOTO: https://www.poz.com/article/hiv-efavirenz-intermittent-16959-8019

Thread:
Every Other Day: https://forums.poz.com/index.php?topic=72189.msg

Thread: Fours days a week
https://forums.poz.com/index.php?topic=72799.msg

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