4 Days a Week of Antiretroviral Treatment Enough?

[Jim Allen]

Reminds me a bit of the Atripla Taken Every Other Day study Or the FOTO study.
(5 days on, 2 days off)

FOTO: https://www.poz.com/article/hiv-efavirenz-intermittent-16959-8019
Every Other Day: https://forums.poz.com/index.php?topic=72189.msg

Is 4 Days a Week of Antiretroviral Treatment Enough?

Full Poz.com write-up:
https://www.poz.com/article/4-days-week-antiretroviral-treatment-enough

In Short:

Prior studies have clearly shown that “drug holidays” that involve interrupting treatment for weeks or months are dangerous. This allows the virus to come surging back, damaging the immune system and triggering inflammation that can contribute to a host of non-AIDS conditions—even if therapy is resumed before the CD4 count drops. It can also lead to drug resistance. But less is known about treatment breaks lasting a few days in the era of more potent drugs with a higher barrier to resistance.

Roland Landman, MD, of Université Paris Diderot, and fellow investigators with the QUATUOR study asked whether intermittent maintenance therapy could improve the convenience and tolerability and lower the cost of antiretroviral treatment for people who have achieved viral suppression on a standard regimen.

This open-label randomized Phase III trial included 636 participants from multiple centers in France who enrolled between September 2017 and January 2018.

At the start of the study they had undetectable viral load (below 50 copies) on a three-drug regimen containing an integrase inhibitor (48%), non-nucleoside reverse transcriptase inhibitor (NNRTI; 47%) or protease inhibitor (6%). More than 70% paired this with tenofovir disoproxil fumarate/emtricitabine (the drugs in Truvada) or tenofovir alafenamide/emtricitabine (the drugs in Descovy). They had been on antiretroviral therapy for a median of seven years, with viral suppression for six years, and they had no evidence of drug resistance.

Participants were randomly assigned to either stay on their daily regimen or take the same medications for four consecutive days followed by three days off.

At 48 weeks, both groups had a high rate of continued viral suppression: 95.6% in the four-day group and 97.2% in the daily group. This difference was not statistically significant, meaning it could have been driven by chance. There was also no significant difference in the occurrence of viral “blips,” or single detectable viral load measurements, in the two groups. These findings demonstrate that the four-days-on/three-days-off schedule was noninferior to, or as good as, the seven-day schedule.

Just six people (1.9%) in the four-day group and four of those (1.3%) in the daily group experienced virological treatment failure. Of these, three and one, respectively, developed resistance mutations. No one taking a protease inhibitor had virological failure, while three people taking NNRTIs in both treatment groups did so. Among those taking integrase inhibitors, there were three virological failures in the four-day group and one in the daily group. Treatment failure was not associated with lowest-ever CD4 count, CD4/CD8 ratio, duration of viral suppression or a history of past virological failure..

[harleymc]

I'm going to discuss this with my ID doctor.

[beanstalk]

I feel like taking it everyday is better anyway since it becomes a habit. Having "off days" might increase the chance of you forgetting to take the medication, at least it would for me.

[leatherman]

since it becomes a habit

taking meds mon-thurs would become a habit after a while. People don't accidentally go to work on the weekend when they have a habit of working monday thru friday. Besides if you forgot to take your meds one day, you could count that as one of the "off" days, since there are 3 of those per week.

I think if people in the "old days" could learn and remember to take some meds every 4 hrs and some meds 2 hrs before food and some meds 2 hrs after food (I used to have a chart on my frig to keep track of all that when I was taking about two dozen pills a day) then people can remember to take meds 4 times a week.

I also remember in the "old days" taking 4 AZT pills every 4 hours 24 hours a day 7 days a week. Many people were very sick on that regimen. These days AZT is still used but not in that original dosage because we now know that that dosage was a serious overdose. This study showing that meds are only needed 4 times a week also shows that current dosing schedules are overdoses.

and to be honest, the incredible money savings is worth it. Ryan White programs and federally qualified health centers spend billions on ARVs. That savings in pharmaceuticals could become funding to help PLWH with other issues (housing, food, transportation, mental health, dental). Some funding could even be used to help "train" patients to remain adherent to the 4/3 plan

[Loa111]

Do you think then that with further studies, sometime in the nearer future, that 4 days a week will become that norm?

[fabio]

It might become a norm to the west where they have more treatment options. In my country at least,we don't choose the treatment really. The docs will only do tests on you and figure out what works best and they won't really make you choose unless the side effects are death.
Most of the treatment in my hospital is rezolsta and argiodin. But I'm sure they have other meds for the ones with resistances or severe side effects.
On the matter of the 4 days a week I would be confused probably,compared to the every day pill. It would take some taking used to.

[leatherman]

It might become a norm to the west where they have more treatment options.

this isn't about options but about pill dosage. actually poorer countries, countries with universal healthcare, and countries with fewer med options will probably jump at the chance to cut their HIV med bills by 40%

[daveR]

Certainly puts missing a single dose every now and then into perspective. I hope it gets general approval. I have to pay for my meds and cannot afford the latest regimes. This would make the cost almost half price.

Dave

[fabio]

That is true,didn't think of it like that. It's cost effective and you get left with extra pills as well. They will last longer than a month.

[leatherman]

and you get left with extra pills as well

well, maybe during the first month before the prescription changes over. While the prescription is now for 30 pills a month, the prescription would change to 16-18 pills a month

[fabio]

Hopefully not,they should have put 31 pills,it's not like every month ends on 30 😢😢😢.

[leatherman]

really good answers about how monthly meds are prescribed and delivered:

Because that is how many doses the physician wrote on the script. The order is not for a month's supply, but rather to take w amount for x frequency by y administration for z days. (For example, take 1 tablet once daily by mouth for 30 days)

Perhaps your real question is why do doctors write scripts for 30 pills when 7 out of 12 months in a year have 31 days in them?

Many common medications are packaged as unit-of-use in quantities of 30. Rather than open a bottle and count out pills, rx techs can simply label the manufacturer bottle. This saves time and lowers waste disposal, ultimately cutting expenses.
Many insurance plans see a month's supply as 30 days, regardless of what month we are actually in. Scripts written for anything other than a 30 day supply can get rejected by those plans and cause computer issues that slow down the process of filling your medication.
Some physicians do write scripts for 31 doses (I've seen 34 also, go figure). Ask your MD, they can probably write your script this way if you want. But your rx staff may secretly despise you if you cause us to have a bottle of 29 pills, it messes with the feng shui of the pharmacy!

go read the other 4 answers submitted:
https://www.quora.com/Why-do-pharmacies-give-you-30-pills-as-a-months-prescription-when-7-out-of-12-months-in-a-year-have-31-days-in-them

[Jim Allen]

Personally living in the luxury I don't pay for my meds, everything is fine meaning 4 days a week or 7 makes little difference to me.

Although I would not switch if asked to 4 days based on the evidence so far. I would want a longer follow-up time on people taking 4 day meds before making any change.

[BKKKevin]

One thing I have noticed is on the rare occasion when I forgot to take my meds with diner about two hours later 9-10pm I get a headache like withdrawal that reminds me to take my pill... I wonder how others react when they skip their meds for a day or two?

[Jim Allen]

Well, the study seemed to suggest they managed. Find it interesting about the headache when skipping a dose, easy reminder though to take the meds. Wonder if more people have that?

BTW This literally just popped up in my twitter feed.

i-Base report urges caution over French study only taking ART 4 days a week
@IAS_conference  see: link: http://i-base.info/htb/36517

For days on, three days off is NOT as effective as daily ART: French study results need to be interpreted with caution

Early results from a late-breaker study at IAS 2019 reported that reduced-dose ART had similar outcomes as a switch strategy compared to people who continued taking ART every day. However, this led to multidrug resistance in people with treatment failure and is therefore difficult to recommend, certainly not for people on rilpivirine or raltegravir.

[Mojito]

Wanted to check if anyone has been put on 4 days on and 3 days off HIV drug regime where one takes the ART medicine for 4 days then 3 days off in a week. I was reading through the research done on this where it shows this regime of drugs is as effective in controlling the Viral load as the 7 day drug regime. If someone has started, what has been your experience? Or is it still in trial phase. Here is the link to the research which I'm talking about.
https://www.aidsmap.com/news/jul-2019/four-days-three-days-hiv-treatment-effective-continuous-therapy-french-study-finds

[Jim Allen]

Hiya,

We have a thread open for this here: https://forums.poz.com/index.php?topic=72799.0

It's just a trial, not a new concept as it's been done before, this trial had mixed results.
So it's not something for everyone but that's not a new concept either.

Best, Jim

[Mojito]

Thanks Jim. Till the time a cure comes, this simple regime sound promising especially for those who are lesser fortunate than us and do not have insurance or access to free medicine. Also it would be beneficial for those who are not able to tolerate the side effect. I know this is not a new concept but to me it looks like it has taken a back seat as I did not find enough independent research publications.                                                                                                                                                                                                   

[Jim Allen]

Hiya

I'm merging the threads and I'll have a look for more studies later on when I'm back home. ( Out & about right now)

Personally I strongly doubt FOTO will do much regarding the pricing long term and with mixed results it's going to be critical for correct implication if ever to wider audience although newer meds are developing all the time with more bi-therapy options as well.

(5 days on, 2 days off)
FOTO: https://www.poz.com/article/hiv-efavirenz-intermittent-16959-8019

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

Newer HIV Regimens May Require Less Strict Adherence
ttps://forums.poz.com/index.php?topic=73003.0

i-Base report urges caution over French study only taking ART 4 days a week
@IAS_conference  see: link: http://i-base.info/htb/36517

For days on, three days off is NOT as effective as daily ART: French study results need to be interpreted with caution

Early results from a late-breaker study at IAS 2019 reported that reduced-dose ART had similar outcomes as a switch strategy compared to people who continued taking ART every day. However, this led to multidrug resistance in people with treatment failure and is therefore difficult to recommend, certainly not for people on rilpivirine or raltegravir.

[Jim Allen]

Results published from the French study first presented at 10th IAS Conference on HIV Science (IAS 2019), 21-24 July 2019, Mexico City and discussed in the thread above.

The Lancet HIV, Volume 9, Issue 2, February 2022, Pages e79-e90

https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(21)00300-3/fulltext

A 4-days-on and 3-days-off maintenance treatment strategy for adults with HIV-1 (ANRS 170 QUATUOR): a randomised, open-label, multicentre, parallel, non-inferiority trial

[Matths]

My 5 cents to the discussion are that the authors should have added the fact that the non-inferiority was observed during a 1-year period only. This seems to me not enough to make any recommendations for maintenance treatment given that our life expectancy is (almost) similar to non-HIV affected people, which implicates that we need to take our medicines far longer than a year. In addition, there is no mention of the emergence of any HIV-related and non-HIV-related illnesses during the observation period or beyond. So, it’s for me another example of poor peer-review of a paper that should have not been published in its current content, should have had a much more critical discussion section and should have been much more cautious in its statements to avoid misleading the HIV community by introducing treatment ideas that are (1) not novel, and (2) could result in potentially dangerous negative long-term outcomes for people who choose to “try” such dosing regiments.

[daveR]

With the minimal side effects and normal life span we get from the current treatments I see no reason to switch. On the other hand if you were having kidney issues or something similar then yes, it may be a way to go.

[Da2020]

It does provide me with some sense of relief over the times where I took my pills little later than usual couple of time in the past two years. I agree with Jim that I d personally wouldn't want to switch from daily medication