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

[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

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.

[leatherman]

I felt these things were known and relatively obvious

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]

I never asked but I was thinking there had to be a good reason for the three pill regiment and it works for me.   

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]

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

  lol.

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.

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

[Jim Allen]

Anyhow, I am sure more in-depth insights will be gained over the years ahead as plenty of people recently switched to dual therapy or injectables.

[numbersguy82]

Wow this was all very insightful. To be honest, I think you are on to something there Jim. I think our habits and long term laziness/comfort setting in are the biggest challenges to staying adherent and healthy with our pill taking.

There was a time back in 2010 when I took 3 separate pills and knew each one’s name and what role they played. Fast forward to today, and I just googled if Biktarvy had two medicines or three.

The upside is I no longer think about my diagnosis. If you’d have told me upon diagnosis that there’d come a time when I popped one pill and largely never thought about hiv, I wouldn’t have believed you. Now the pendulum probably needs to swing back a little bit… I’m not getting any younger and well my health should be on my mind.

[daveR]

I discussed the possibility of changing to a two dug regime 12 months ago with my Dr by dropping Abacavir form my regime. Her advice then was to wait and see a bit longer. Looks like she was correct in doing that.

[Jim Allen]

I discussed the possibility of changing to a two dug regime 12 months ago with my Dr by dropping Abacavir form my regime. Her advice then was to wait and see a bit longer. Looks like she was correct in doing that.

My appointments are the opposite; they keep trying to switch me to Dovato, and I keep reminding them that I am not doing that. 

I do understand wanting to drop ABC (Abacavir) 1); I was and still am not overly worried about it. The issue with ABC has been known for years, and I worked it out as a bit of a storm in a teacup years ago; however, as I am older 2) and over the years, meds have improved, I think the time has come to drop ABC, but not for Dovato.

My issue is I want to remain on HAART, not injectables or Dual therapy. However, I don't want anything to do with TAF or TDF, and the point of switching is to drop ABC. It leaves me with very few available options...

1)

Experts recommend statins for all people with HIV aged 40+
https://forums.poz.com/index.php?topic=66320.150

a strong association between recent ABC use and risk of CVD remains
N.J. Jaschinski1, on behalf of the RESPOND study group
1University of Copenhagen, Rigshospitalet, CHIP, Copenhagen, Denmark
https://eacs2021.abstractserver.com/program/#/details/presentations/243

[Jim Allen]

Wow this was all very insightful. To be honest, I think you are on to something there Jim. I think our habits and long term laziness/comfort setting in are the biggest challenges to staying adherent and healthy with our pill taking.

There was a time back in 2010 when I took 3 separate pills and knew each one’s name and what role they played. Fast forward to today, and I just googled if Biktarvy had two medicines or three.

The upside is I no longer think about my diagnosis. If you’d have told me upon diagnosis that there’d come a time when I popped one pill and largely never thought about hiv, I wouldn’t have believed you. Now the pendulum probably needs to swing back a little bit… I’m not getting any younger and well my health should be on my mind.

100% agree. It is part of the testament to how good HIV treatment has become over the years, and I truly suspect that a return to more strict adherence is needed when switching from HAART to Dual therapy, again I have no evidence of this; it is just speculation based on some data from the mid 2010s and my limited observations under PLHIV, and how lacks we have become and now this low failure rate of dual therapy.

Although, I did miss this one from October:

Intermittent dosing on HIV dual therapy leads to a higher rate of treatment failure
https://www.aidsmap.com/news/oct-2023/intermittent-dosing-hiv-dual-therapy-leads-higher-rate-treatment-failure

[Dogman]

The upside is I no longer think about my diagnosis.

I hope I can get to this point. I've taken a dive recently back into it invading my thoughts constantly. No valid or logical reason.

[Jim Allen]

I hope I can get to this point. I've taken a dive recently back into it invading my thoughts constantly. No valid or logical reason.

Sorry to hear that. We are here for you, hugs.

[numbersguy82]

Intermittent dosing on HIV dual therapy leads to a higher rate of treatment failure
https://www.aidsmap.com/news/oct-2023/intermittent-dosing-hiv-dual-therapy-leads-higher-rate-treatment-failure

Not for nothing but I’d be too afraid to sign up for a study like this. We are so conditioned not to miss doses and to ensure daily dosing occurs. I guess there isn’t progress without some measurable risk…

[Jim Allen]

Not for nothing but I’d be too afraid to sign up for a study like this.

They are very brave or ... https://www.youtube.com/watch?v=yycFr3YeKFM
Anyhow, you will not catch me pissing about with dosing.

[CircularNatural]

You guys are giving me a bit of a creeps with this chat, LOL.
I´m poz since 2021 and sort of chose to go for Dovato (dol + 3tc).
Have been undetectable ever since but of course the fear of potential resistance comes and goes. I´m quite obssesive in relation to adherence, though, which helps a lot.
I hope they keep on making progress and advances on long term safety in this matters, though.
So far, I´ve always understood that so long you keep the virus at bay there shouldnt be a resistance, unless you adhere poorly. In that sense, I hope that if I keep on being orderly regards my Dovato daily intake, I shouldn´t have a problem.
Hope that works that way for all of us.
Best regards!

[leatherman]

So far, I´ve always understood that so long you keep the virus at bay there shouldnt be a resistance, unless you adhere poorly.

resistance happens when HIV are taken haphazardly.

When you take ARVs, the meds get into your system and stay there for a certain amount of time before leaving your system. We take meds daily to keep that level up enough that HIV doesn't learn to resist the medications. Skipping a dose won't do it. Even skipping a couple. However if you take the meds haphazardly - like 2 days on, 4 days off, 3 days on, 1 off, 2 days on, 3 off - and the levels of meds keeps dipping too low, HIV can mutate to resist medications.

As long as you stay at 95% adherence and above, resistance will never happen and theoretically you can stay on the same meds forever.

[Jim Allen]

if you take the meds haphazardly - like 2 days on, 4 days off, 3 days on, 1 off, 2 days on, 3 off - and the levels of meds keeps dipping too low, HIV can mutate to resist medications.

As long as you stay at 95% adherence and above, resistance will never happen and theoretically you can stay on the same meds forever.

👍

[Jim Allen]

You guys are giving me a bit of a creeps with this chat, LOL.

I'm not supprised. That why I added a note in the first post to avoid freaking people out
Although, this thread is nowhere near as bad as the conversations during the monthly meetings

[wardp]

6yrs on lamidivuine and neveripine.i rarely miss a dose maybe once or twice a year. All good .touch wood.