Adherence to Antiretroviral Therapy and Virologic Failure A Meta-Analysis

[Jim Allen]

Interesting read, thought i would share. Now I have not had the time to read it fully but will.

The often cited need to achieve ≥95% (nearly perfect) adherence to antiretroviral therapy (ART) for successful virologic outcomes in HIV may present a barrier to initiation of therapy in the early stages of HIV.

This meta-analysis synthesized 43 studies (27,905 participants) performed across >26 countries, to determine the relationship between cut-off point for optimal adherence to ART and virologic outcomes.

Meta-analysis was performed using a random-effect model to calculate pooled odds ratios with corresponding 95% confidence intervals.

Of a total 27,905 participants, 22,740 participants had a viral load and adherence measurement; 7056 (31%) had virologic failure. Overall, 3464 of 15,067 participants with optimal adherence to ART (23%), and 3592 of 7673 participants with suboptimal adherence (47%) participants had virologic failure (Figure ​(Figure2).2). The pooled odds ratio for virologic failure for optimal adherence compared to suboptimal adherence was 0.34 (95% CI: 0.26–0.44).

CONCLUSION
Irrespective of the cut-off point for optimal adherence, our findings support the tenet that optimal adherence to ART is associated with positive clinical outcomes. The threshold for optimal adherence to achieve better virologic outcomes appears to be wider than the commonly used cut-off point (≥95% adherence). Though patients taking ART should be instructed to attain ≥95% adherence, apprehensions of slightly lower adherence should not deter prescribing ART regimens at an early stage of HIV infection.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839839/

[paintedroom]

Which begs a niggling question that i haven`t allow crystallize in my bonce..till now.
Are there members here who have maintained 95% - 100% adherence and had resistance ? I wonder if there is an approximate number out there ? And if so is this an incidence that happens after many years taking specific drugs ?

[Jim Allen]

Ok my comment does not change the question you have, and your question is fine of course. .

But i will comment and its just to clarify as I don't want anyone new reading this thread and shitting themselves.  I should have anticipated the concern before i posted though...

Virologic failure rates of course do not equal drug resistance, Virologic failure rates is simply is when antiretroviral therapy (ART) fails to suppress and sustain a person’s viral load.

Many factors that can contribute to virologic failure including, yes drug resistance is one of them, but poor treatment adherence, (despite reporting adherence) underlying medical conditions, underlying medical treatments (interactions) and/or poor absorption are all examples and there are more, and thankfully drug resistance is tested (most of the time) before we start treatment.

Jim

[paintedroom]

Yes Jim,i wondered about that responsibility to new members here myself..heck i hadn`t allowed myself to really think about it, as one`s emotional economy sometimes only permits so much truth per term,especially if one has had a particularly tricky year.

Feel free to vaporize my question.

[Jim Allen]

No, look its a fine question.

I just don't have an intimidate answer other than, yes it can happen ... but extremely rare .

Look I can at least recall a thread where someone claimed this and I can look later when I am back (Going shopping) however key to remember is many members are on treatments for years, some a decade by now without such issues and its a really really rare concern with correct adherence more related to older classes of meds.

Most studies and cases I read are pre- 2011/2009 on the subject often other illnesses played a factor and since then newer meds including more frequent testing for resistance before starting treatment and better understanding of the role of adherence really changed this.

I will post the details but take it with a gain of salt on the resistance part.

[paintedroom]

Thanks so much for the reassurance as always.

Treat yourself to a fine cup of coffee and a chocolate eclair while you`re out shopping..on me of course.

[Jim Allen]

chocolate eclair

Ice-cream with today's weather great way to end the day.

So long answer short is I would not worry about resistance, look as long as you stay adherent to your meds you have done your part and it will be grand. Now if one day, in many years to come you have to switch so be it.

Take away is, Virologic failure rates of course do not automatically equal drug resistance as Virologic failure can have many reasons.

Resistance, and yes drug resistance can happen, however most cases new resistances is linked to poor adherence this is within your control, keeping in mind a lot of studies is "self reported adherence" far more often its things like poor adherence, poor absorption, Drug-drug interactions, other illnesses and of course pre-existing resistance - that's life.

https://www.poz.com/basics/hiv-basics/hiv-drug-resistance

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704206/ (2009)
Antiretroviral medication adherence and the development of class-specific antiretroviral resistance

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065011/ 2016
Antiretroviral Failure Despite High Levels of Adherence: Discordant Adherence–Response Relationship in Botswana

Conclusions - Very high rates of adherence were present in this setting, yet virological failure occurred nonetheless. Future work should explore other factors that might explain treatment failure in the setting of high levels of adherence

Slightly older  May 2005; Content reviewed January 2006 but still a good read on adherence and virological failure whilst adherent, perhaps more relevant on older drug classes - people still take them.
http://hivinsite.ucsf.edu/InSite?page=kb-03-02-09

I could find more but you catch my drift.

Now i know someone will be along to disagree shortly with my post 

Jim

[paintedroom]

Thanks again for all your input.Great to have it all condensed into one comment.

[harleymc]

I had a treatment failure due to resistance circa 2005. my virus had resistance mutations to all existing classes of ARTs.

I was adherent BUT there were was a massively different historical context to my medication failure than in today's world.

The primary difference was that I had been on a series of what were effectively monotherapies for 15 years prior to my failure.

In 1990 I had started on AZT, then after 18 months (plenty of time to develop resistance to one drug)  DDI was added in. The pattern of adding one new medication was repeated right through the triple combination therapy revolution and into the 2000's.  I never had a novel triple therapy until 2007.

Since having a novel triple therapy I've never had a viral load blip, although I have change medications.

[MitchMiller]

What's amazing is how many in the study reported sub-optimal (< 95%) adherence to medication.  That means they missed at least 20 doses in one year. 

[Jim Allen]

Virologic failure, due to suboptimal adherence is indeed a big part of the overall group.

It is indeed a bit shocking to see a such a high number with suboptimal adherence but that said I do suspect that the reasons people in the real world miss meds vary widely from things like social, economical,and other health/mental health problems. The lack of support, lack of education, and type of meds being taken (pill burden) all could play a real role in adherence challenges . 

I suspect better support would help address the high number of people with adherence challenges leading to Virologic failure. It makes up the larger group of people who experience virologic failure in the collective study and it can pose real challenges for the individuals in terms of, progression and illness, possible future treatment problems and on a side note prevention challenges of course.

Jim

[leatherman]

Take away is, Virologic failure rates of course do not automatically equal drug resistance as Virologic failure can have many reasons.

Oct 2015 I had virologic failure after 25 years of HIV meds and nearly 10 years adherent to the same regimen. I had a huge spike in VL (25k rising to 60k) over a 4 month period. A genotype test revealed I had not developed resistance (although I do have a resistance profile to quite a number of meds, especially many of the earliest meds from the 90s) and that my regimen was actually still effective. Needless to say though I still switched regimens (i has been wanting to lower my pill burden and try to counteract side effects I was experiencing just before this unexplained VL spike happened) and within 2 months was back to UD.

What's amazing is how many in the study reported sub-optimal (< 95%) adherence to medication.  That means they missed at least 20 doses in one year. 

not so surprising in the real world. I know a number of people who have had <90% adherence with no issues. Keep in mind medication dosages as based on an average. Someone with a fast metabolism or someone with low weight may actually need more or less medication. As there simply isn't enough funding for therapeutic drug monitoring for everyone, we all take a generic dosing that could, or could not, be the right amount for our individual needs - although for most people the dosage amount is the correct amount.

[bocker3]

Which begs a niggling question that i haven`t allow crystallize in my bonce..till now.
Are there members here who have maintained 95% - 100% adherence and had resistance ? I wonder if there is an approximate number out there ? And if so is this an incidence that happens after many years taking specific drugs ?

My question to you is -- why are you concerned about this?  If this happens it is beyond your control.  All you can do is maintain adherence to your meds, continue to get your VL checked and then, if something were to go astray, you and your doctor would sort out the next steps.

Asking for anecdotes on here will only fuel fear, worry and angst.  What happens to one person (or even a number of people) does not mean it will happen to you.  For instance, there are people who have fallen from a window 6 stories high and lived -- I wouldn't assume that I would have the same outcome.  There are people who trip over a curb, fall and die from a brain bleed -- again, I wouldn't assume that tripping over a curb would kill me.

Bottomline -- try not to worry about things over which you have no control.  Take your meds, see your doctor and, in the meantime, enjoy your life.  We are all going to die sometime -- we don't know when, so why waste your time with unneeded worry!!

Hugs,
Mike

[paintedroom]

Thanks Mike for sound advice.
Yes i understand the rational approach..tis the irrational that creeps around the fringes of my head whispering doubts.

Hope all well,Onward...

[paintedroom]

Sorry Mike,was rushing out this morning and missed your essential point - worry and angst for any new people reading.You`re quite right.If Jim or any other moderator wants to scrub my comments,no problem at all.

[Jim Allen]

You`re quite right.If Jim or any other moderator wants to scrub my comments,no problem at all.

No, its grand - I should have anticipated the concern before i posted the initial topic and besides its good item to discuss and put to rest so anyone else with the that concern can read the same and put it behind them.

If we only post or allow happy thoughts or discuss positive news than we in my eyes will not be much better than dozen or happy happy all is good in the world groups, that simply make me want to puke, if i am frank 

Not discussing it would be negative, the fact we did is great.

Jim

[bocker3]

Sorry Mike,was rushing out this morning and missed your essential point - worry and angst for any new people reading.You`re quite right.If Jim or any other moderator wants to scrub my comments,no problem at all.

Actually, I was referring to you -- though, it is applicable to anyone, including newbies. 

Looking for examples of things in others gives false security and/or false fear -- because anecdotes don't necessarily apply to anyone except the person who experienced it.  It's human nature and we all have done it, myself included, but it is important to always keep in mind that what happens to me does not mean it will happen to you.

M

[daveR]

A very good worth while thread. When I was given my first batch of pills I was given no advice at all from the hospital, all of my information came from the internet via google. I had no idea about adherence, which includes food requirements as well as actually taking the pills daily. Always good to see the honest information, not just the sugar coated feel good information. The truth concerning lack of adherence and the consequences should be well known.

Dave

[Expat1]

Mitch, sometimes Adherence issues are beyond the control of a patient.  Due to drug stockouts, insurance issues, incarceration, accidents that incapacitate a person.

My partner missed about 60 days of medicine in the past 3 years.   Once to jail and the other due to having a motorcycle accident and being in a coma.  The Doctors did not want to give him anything while in a coma.  The jails in some places violate human rights in refusing to treat hiv.  So while he has never failed to take his medicine.  There were times when he simply couldn't.

Thankfully, when restarted on the medicines the VL was undetectable after 3 months each time.  (Note the Dr would not do a VL test prior to restarting.  Genotyping is seldom done here also.)  The doctor stated that they just restart the drug, then check in 3 months to make sure it is still working. 

[Jim Allen]

Indeed adherence is sometimes outside someone's control. However adherence message for those with access is a no brainer and it was interesting to see virological failure from reasons other than adherence.

I think this report just reinforced that treatment failure can and does happened, biggest  reason is within our own control. But overall reasons i am sure are varied and it's not finger pointing. Besides poor or incorrect treatment adherence,  things like drug resistance, drug or , absorption issues or other health conditions/drug interactions all I am sure play a role.