POZ since 1994 Resistant to many classes. WTF..

[stevetool]

Hi everyone,

Resistance to many drug classes which was reveled during my last few visits to HIV specialist using a GenoSure. WTF? Viral load of 9000 to 11000 and Tcell count stable at high 350s. I never take drug holidays and Im methodical about taking me meds daily. My medication regimen during the Genotype was Tivicay & Descovy

GenoSure results:

NRTI class
Resistant To ALL with a heinous amount of mutations too long to list

Integrase class (resistant to all)
RALTEGRAVIR / Isentress      (predicted)
ELVITEGRAVIR / Stribild        (predicted)
DOLUTEGRAVIR / Tivicay      (predicted)
BICTEGRAVIR / Biktarvy        (predicted)

NNRTI Class
Doravirine / ‎Pifeltro     (Sensitive) Mutations - K101E, G190A, D237E

Efavirenz / Sustiva      (Resistant) Mutations - K101E, G190A

Etravirine / Intelence   (Sensitive) Mutations - NONE

Nevirapine / Viramune (Resistant) Mutations - K101E, G190A

Rilpivlrine / Edurant     (Resistant) Mutations - K101E


Protease Inhibitor Class
Alazanavir / Reyataz     (Resistant) Mutations - K20R, E35D, M36I, I50L, T74S, V82M, I85V

Darunavir / Prezista      (Sensitive) Mutations - K20R

Fosamprenavir / Lexiva (Sensitive) Mutaions - E35D, V82M

Indinavir / Crixivan       (Sensitive) Mutations - K20R, M36I, V82M, I85V

Lopinavir / Kaletra        (Sensitive) Mutations - K20R, T74S, V82M

Nelfinavir / Viracept      (Sensitive) Mutations - E35D, M35I, T74S

Ritonavir / Norvir         (Sensitive) Mutations - K20R, E35D

Saquinavir / Invirase    (Sensitive) Mutations - K20R, E35D, T74S

Tiprenavir / Aptivus      (Sensitive) Mutation K20R, E35D, M36I, V82M


So far my Doc suggested the use of

(1st option) Fostemsavir (Rukobia) as an addon to my current treatment (Tivicay & Descovy)

(2nd option) Darunavir (Prezista) Doravirine (Pifeltro).

(3rd option) Etravirine (Intelence), Ritonavir (Norvir) & Darunavir (Prezista)

I tried Intelence in 2010 and it caused Immune reconstitution syndrome (hello angry butt rashes). I was quickly taken off of it which explain having no resistance to it.

And my fear with Fostemsavir (Rukobia) is developing early resistance mutations to it it its going to be a new line of drug class.

I have been researching HIV resistance non stop for 5 days str8 and I cant seem to wrap my head around it.

My questions are,
(a) is Fostemsavir (Rukobia) going to be a new drug class for all HIV patients (treatment naive and treatment experienced patients)? Or is it always going to be considered a "savage therapy." And should I have concern about developing early resistance to it?
 
(b) Based on my Genosure what would you do? Or is there anyone who can make sense of these regimen choices based on my genosure and my doctors suggestions?

Im devastated. Been through such a hellish couple years including Large B Cell lymphoma, 5 months of chemo (cured it so far), Covid isolation, Mutable surgeries for my dog requiring 24/7 rehab (he's my only life line). 15 plus years of Lipoatrophy (no butt, sunken cheeks) and life long metabolic issues (thanks Zerit! Thanks drug companies who take no responsibility!). "well your alive" isn't an answer....

Honestly I feel like just stopping the HIV drugs and letting nature take it course. Im exhausted and need some support and hopefully some insight to these questions. I have no faith in my doctor although he is considered one of the best Infectious Disease Docs in my city.

Anyone...please...

[Tonny2]

           ojo.    Hello there...I’m sorry about your situation. We, both, have, well, I had, two things in commun, diagnosed in 1994 and, I was sent home to wait for an opportunistic infection to kill me due to resistance in the summer of 2006...I know what you are going through, but, you have to do what you have to do, try the “salvage treatment” as I did back in 2006...in October of that year the doctor offered me such treatment, I had nothing to lose, so, in January 2007 I started: DARUNAVIR/NORVIR, INTELENCE in March same year, my cd4 went up from 36 to 360 and for the first time since my dx in November 1994, I was uD, the doctor added ISENTRESS that month...now, you can take INTELENCE because your immune system is “good”, so, I
guess, it’s one of your options...please don’t think that you will get resistance to the new class of drugs, just try it and don’t worry until you have something to worry about...I hope my reply helps you...be strong...best wishes and don’t throw the towel after fighting for all these years, I haven’t done it even having lost almost my eyesight to CMV RETINITIS, and, I’m here, taking me forever to type this message...hugs.    ojo

[Tonny2]

        ojo.       It’s me again...I forgot to let you know that I’m still taking the same treatment since 2007 and my cd4 level is 600-800, 33% and still UD...you need ñ, not only, skip doses, but take your meds as directed, mine are supposed to be taken with food...best of luck and, please, keep us posted...hugs.             ojo

[stevetool]

OJO thank so much for the encouraging words, for reading my post thoroughly and for reminding me there’s others out there just like me.

So in 2006 they sent you home to die (horrifying I’m so sorry), then, in early 2007  they offered salvage therapy I.e intelence, prezista and Norvir ? And you’ve been on that regimen from 2007 to 2020 (with the added Isentress) achieving t-cells in the 600/800’s and UD??? This whole time?

Am I getting this right? This seems very encouraging.

I am resistant to Isentress but...still...

[stevetool]

...I have no resistance to Isentress, Only one resistant mutation to prezista, and 2 resistant mutations to norvir. But they all show as "sensitive" or "all systems go" in my genotype. So they are still strong options.

My fear with  Fostemsavir (Rukobia) is it only recently been approved be the FDA (July 2020). I'd like to see how it fairs in the general public for a year before jumping on it. Although I would change my mind on that if I knew Fostemsavir (Rukobia) was specially only for savage therapy.

I still cant find the answer to the question - is Fostemsavir (Rukobia) the next front line drug therapy class? Or is it savage only therapy. I going to ask my doc tomm.

[Tonny2]

          ojo.        Hi again...yes, everything I replied to you happened to me in August 2006. I was told there was no more medications for me due to resistance, in October same year, my doctor called me to let me know that a pharmaceutical company was offering to people like me (history of resistance) a “savage treatment”, it wasn’t approved by the FDA yet (I got the treatment free for a year), and it saved my life...rukobia, first time of heard about this med, according to what you mentioned, “savage treatment”, it’s the same thing they used to call my treatment, the only difference is that rukobia is already approved by the FDA...talk to you doctor about the treatment I’m taking, it might help you if you want to wait for rukobia experience by others. Your cd4 are good, still, have supposed yo are ud, aren’t you?, if not, I would go ahead and start the new med in combination with other meds you are not resistance to...I had no choice back in 2006, cd4 36 and VL in the Mullins, that’s why I decided to take the “savage treatment”...best of luck...hugs

Ps. English is my second language and I’m legally blind, sorry for the mistakes

[leatherman]

“savage treatment”

"salvage" treatments sometimes are taking more than just regular 3-med regimens. Adding a 4th or 5th med, ones that you might even be mildly resistant to, can help keep HIV under control

...I have no resistance to Isentress, Only one resistant mutation to prezista, and 2 resistant mutations to norvir. But they all show as "sensitive" or "all systems go" in my genotype. So they are still strong options.

My fear with  Fostemsavir (Rukobia) is it only recently been approved be the FDA (July 2020). I'd like to see how it fairs in the general public for a year before jumping on it. Although I would change my mind on that if I knew Fostemsavir (Rukobia) was specially only for savage therapy.

I still cant find the answer to the question - is Fostemsavir (Rukobia) the next front line drug therapy class? Or is it savage only therapy. I going to ask my doc tomm.

wikipedia https://en.wikipedia.org/wiki/Fostemsavir
"Fostemsavir, sold under the brand name Rukobia, is an antiretroviral medication for adults living with HIV/AIDS who have tried multiple HIV medications and whose HIV infection cannot be successfully treated with other therapies because of resistance, intolerance or safety considerations.[1][2]

The most common adverse reaction is nausea.[1][3][2] Severe adverse reactions included elevations in liver enzymes among participants also infected with hepatitis B or C virus, and changes in the immune system (immune reconstitution syndrome).[1]"

Fostemsavir is an HIV entry inhibitor and a prodrug of temsavir (BMS-626529).[medical citation needed] Fostemsavir is a human immunodeficiency virus type 1 (HIV-1) gp120-directed attachment inhibitor.[4] It was approved for medical use in the United States in July 2020.[1][3][4]"

Cobicistat https://en.wikipedia.org/wiki/Cobicistat
"Cobicistat is a drug analogue of ritonavir, in which the valine moiety is exchanged for a 2-morpholinoethyl group, and the backbone hydroxyl group is removed. These changes effectively eliminate the anti-HIV activity of ritonavir while preserving its inhibitory effects on the CYP3A isozyme family of proteins.[6] Cobicistat is therefore able to increase plasma concentration of other coadministered anti-HIV drugs without the risk of causing cobicistat-resistant mutations in the HIV virus"

cobicistat is a booster like norvir. the combo of darunavir/cobicistat is marketed as Prezcobix by Janssen

[stevetool]

I meant to say I have NO resistance to Intelence.
I DO have resistance to Isentress.

But hearing that Tonny2 stayed on intelence, prezista, Norvir, Isentress, and has suppressed his virus for 12 years is very encouraging. As I said in my first post. My T-cells's are in the high 300s and my viral load is 11000 atm.

Also thanks leathermanfor the info about Cobicistat, darunavir/cobicistat & Prezcobix. I was unaware of cobicistat & Prezcobix and my doc didnt even mention it during our talks

I have a call in to my current ID doctor today and made an additional appointment with another ID HIV specialist on Friday for a second opinion.

Both of your responses have given me lots of hope! I will update on whats happening as it happens here. Thank you thank you thank you!

[stevetool]

Ok...Spoke to in ID Doc. Not feeling so confident.

The regimens im presented with are:
Prezista Norvir (as booster) and Intenece
OR
Prezista, Cobicistat (as booster) and Intenece.

The amount of conflicting information regarding the use of boosters such as Cobicistat or Norvir with this regimen is outstanding, mainly because of Intelence. Studies from 2015 to 2020 show conflict, while studies prior to 2015 dont.

Apparently taking Norvir or Cobicistat with Intelence and Prezista cause significant reductions of Intelence and Prezista concentrations depending on which study you read.

Example - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702580/
Although a phase II single arm study in HIV-infected subjects of darunavir 800 mg/ritonavir 100 mg daily plus etravirine 400 mg daily showed no significant changes in either darunavir or etravirine with coadministration,21 an open-label, fixed sequence study in 30 HIV-infected subjects showed marked reductions in cobicistat (30% reduction AUC, 66% reduction in C24h) and 56% reduction in darunavir C24h with coadministration of darunavir 800 mg/cobicistat 150 mg and etravirine 400 mg daily compared to darunavir/cobicistat administered alone.22 The darunavir/cobicistat monograph states that coadministration of etravirine is not recommended.23 If therapy with both etravirine and darunavir is required, ritonavir may be the preferred booster.

My doc is leaning towards Cobicistat as the preferred booster, but I've found at least 6 studies showing Norvir to be the preferred booster. To make this even more complicated, Ive also found other studies showing Cobicistat to be the preferred booster with this regimen.

Oddly all studies using Prezista and Norvir or Cobicistat (as booster) without Intellence showed increases in Prezista concentrations and have wonderful clinical results. But this is considered a dual therapy model. I think with my resistance profile, I need a minimum of 3 antiviral medications.

I am resistant to Isentress, so the super well studied and effective combo of  DARUNAVIR/NORVIR, INTELENCE/ISENTRESS is not possible for me.

Again Im resistant to all NRTI's, sensitive to only 2 NNRTI's (Intelence & Pifeitro) and sensitive to all PI's except reyataz & Aptivus.

Ive emailed my doc about 1000 times. He is considering all the studies and conferring with colleges.

Im at a loss here. And im cross eyed from reading studies that conflict with each other.

Anyone have any thoughts?

[Theyer]

It would be useless if I tried to make comments about your drug choices ,For past 15 to 20 years I have with vigour found Docs who are sane and are able to communicate once found I go alone with there advice. It’s a method.
What I do want to say was your description of your awfull year I do recognise,
So  I know the feeling of    Fuck it let nature do it,s thing.
          Reading your descriptions,has reminded me of my own process ,I get into that Zone when I am overwhelmed and then the only thing that works( for me) is a brief holiday from it all. And during the holiday wait to see if a decision surfaces. You,ve had five days of research ,enough to make the freelance researcher give there self a weekend.
 Be with your dog , you still have choices and you will make a decision but first have a break from all this shite and try to count some daisies.
Best wishes ,m

[stevetool]

Ok so...after much review I decided on Prezista, Intelence and Norvir (as booster). 

Using cobicostat with Intelence isnt even suggested by the company who make all three of these medications (Jannsen). Apparently the co-administration of cobicostat with Intelence causes weaker concentrations of Prezista which can potentially be a setup for Prezista resistance. This is also confirmed by 3 studies carried out from 2016 to 2020. And more clinical trials are underway.

This is not the case for using ONLY Prezista and Cobicastat (dual therapy).

Ive committed to viral load tests every three weeks. I should have first VL results in about 2 weeks.

Just updating whats going on. Im thrilled about none of this...

Just a heads up on what im doing.

[leatherman]

best wishes on this being the right combo for you!!! 

[Tonny2]

                 ojo          hello again...I'm glad you finally decide to take that new treatment, as I told you before, I was offered that treatment as a salvage treatment, I had just 36 cd4, now, after 13 years with the same treatment plus raltegravir, my cd4 is 600-800, 39% and still UD....Please keep us posted and best of luck....             ojo

[Snowangel19]

Hey-
I’m circa 94 too. I had resistance in 2000. It is so scary to hear, I would definately reach out to drug reps for studies and do whatever you can to alleviate your stress level. I used and still use weed, it helps so much with nausea, sleep, anxiety. 
I’m going to Boston hospital this week for a study,I will ask if they know of anything if you want.
PM me whenever you want
Stay strong ❤️

[stevetool]

Thanks Snowangel19. What are you on now? And what trial are you going for?

Been on the new reg (Intelence Prezista & Norvir) for almost a month. Feel sick to my stomach most of the time and its as if every disc & bone issue I ever had has resurfaced simultaneously.

This combo is giving me major physiological issues too .

I take 4mg's of Diazepam for sleep (5 years) and use marijuana daily.

Apparently this HIV drug combo and all its "boosting" has put my levels of diazepam through the roof and has eliminated any enjoyable effect of marijuana used to have on me....

I Just feel the sedating crashing part of weed now and overly sedated from diazepam. I cut my diazepam dose to half (2mg's) and still feel over sedated. I have to take the diazepam reduction slow.

One forum member posted that diazepam is increased by 2000% on this reg. so tapering is almost impossible if its concentration is increased by the thousands.

I got my t-cell and VL tests done yesterday..awaiting results.

I could complain forever here. But that's enough for now...

[Tonny2]

                              ojo      hello again...I suppose your doctor knows what other meds you are taking, if not, you have to tell him what you are taking because norvir increases the levels of other meds. talk to your doctor....about the side effects, I guess, in our situation, being resistance to other meds, we have too bite one of our nuts", put out, and give it time so your body gets used to the new meds...hang in there. please keep us posted and you can complain or rant as long as you want, we are here for you....hugs                                                                         ojo

[stevetool]

Tonny2 - Yes yes of course. My doctor is aware I use medical marijuana and he's the one who prescribes me the diazepam. I was mostly responding to Snowangel19's comment about marijuana in that post.

From what im understanding tho from these forums, Mental fog, Anxiety and extreme Fatigue are common place for all three Norvir, Prezista & Intelence.

I have no zest for life. I have dread type thinking. No feels at all. These aren't symptoms I typically experience. Its definitely the meds.

[Tonny2]

         ojo.        Hi again...I’m sorry you are going through those feelings, thankfully, I haven’t felt what you described in my 13 years of taking these meds, as a matter of fact, in my almost 26 years of taking meds, not even with efavirenz, never felt like you are feeling. Anyway, have your doctor checked your testosterone levels?, it might help for your fatigue if your levels were to be low. I hope you start to feel better as your body adjusts to your new meds...hugs.                                                        ojo

[Grasshopper]

Tonny2 - Yes yes of course. My doctor is aware I use medical marijuana and he's the one who prescribes me the diazepam. I was mostly responding to Snowangel19's comment about marijuana in that post.

From what im understanding tho from these forums, Mental fog, Anxiety and extreme Fatigue are common place for all three Norvir, Prezista & Intelence.

I have no zest for life. I have dread type thinking. No feels at all. These aren't symptoms I typically experience. Its definitely the meds.

From personal experience I know that prolonged use/smoking of marijuna gives ME  "mental fog", especially the "indica" versions

[stevetool]

Yes Ive been using medical marijuana since I had (and beat) cancer a couple years ago. Im very familiar with the strains sativa & indica and I have both. In fact its been a wonderful tool for me. I enjoy it immensely & use a small amount daily.

Since I started the new HIV reg, when I use marijuana, the high is nothing more than a drone kind of feel. Like you would feel at the end of a couple hours using marijuana.

Ive read studies involving HIV boosting agents & marijuana. They say that the combo reduces certain levels of cannabinoids and increases others. 

I know the only new introduction in all of this is the HIV meds.

From what im reading online & on these forums, many folks struggle.

"Mental fog, Anxiety and extreme Fatigue" are quoted in the literature of all 3 of these meds individually, let alone all 3 combined.

I was just hoping to find folks who experienced Mental fog, Anxiety and extreme Fatigue symptoms when starting this type of HIV medicines.

[Snowangel]

 Hi there!

I am on Prezista and tivicay now.  It is a study to see if there is a difference with inflammation around the heart and arteries of women who are positive and those who aren't.

Diazepam sounds like an ass kicker.  I stick to high sativa's and they help me keep going during the day.

When do you get your results?

[stevetool]

Results should be in the next few days. Diazepam is what it is.

Been taking it for sleep for years. 4mgs is considered a low dose and only take at bedtime. I dont even feel it but it does help me sleep.

Since I started this new HIV med reg, I cut the Diazepam dose in half which is suggested because all the boosting going on with the HIV meds. Its common knowledge. Many posters on this forum talk about it too.

I have been feeling better. I guess my body is getting use to the new HIV reg (Intenece, norvir and presizta). Or maybe I had a slight flu when I started.

Im freaking out waiting for the results. Im freaking out worrying how long until I become resistant to this HIV med reg...

Thanks to all who have been hangin with me on this.

[stevetool]

Ok results are in. (Drum roll....)

Not much change on my cd4 (330).

But my VL is down to 300 copies (from 10,000) in three weeks of being on new regimen!

Good news! I have a virtual visit from my dr today at 5pm.

I update more once I chat with Dr. There might be some switching of things.

[Tonny2]

       ojo.     Hi...blood work after three weeks of treatment?, well, I guess your doctor knows best, in my case, remember same situation like yours, resistance, I had to wait three months eve though I has VL in the millóns and 36 cd4, I see my ID specialist at the Cleveland Clinc, anyway, as I told you before my VL was UD and cd4 361 after three months of the same treatment you are taking now...good luck with your doctor’s app and keep us posted...hugs

[stevetool]

Thanks Tonny2

Yea that sounds like a lot to go thru back then tonny2. Thankfully, eventually, you found  the key.

[stevetool]

Hi everyone. Ok so second opinion Dr. Suggests Rukobia,
Maraviroc & Symtuza.

I'm currently going thru hell with my current reg (Prezista norvir and intelence) but i'm currently indetectable.

They are running special tests to see if im a fit for Maraviroc, which should be done soon.

At this stage of my journey i have to except protease inhibitors will be the back bone of my treatment. And all the "boosting" that happens with PI"s & Cobicistat (in my case) is just part of the deal.

BUT does anyone have any experience with Rukobia, and or Maraviroc they's like to share ? Or could anyone point me to a forum member that might?

Thanks

[Tonny2]

          ojo.        Hello again!...mmmm, I was wondering what kind of “hell” you are going with your recent treatment, darunavir/nor ir and I tele ce?, I know everybody reacts differently to treatment but, I’ve been taking same treatment for 13 years and never had a problem, anyway...I’ve never taken rukobia nor maraviric, but I have a friend taking maraviric for awhile and he said he haven’t had any side effects...wishing you the best and hoping you come to terms that, whatever “hell” you are going through, remember that it’s better that no taking meds...hugs and please keep us posted.                             

[stevetool]

Tony 2 "whatever hell im going though" is norvir and intelence. My personal issues with them is pretty clearly mentioned here in the thread and very well documented by others in this forum and beyond.

Ive been on the "new" meds (Symtuza & Rukobia)
for almost a week. No stomach issues and the cobicistat (instead of norvir) seems to be much more tolerable.

Im still waiting pending test results for the Maraviroc. Of course these tests "should" have been done before my viral load dropped, but my Dr's didn't catch it (no surprise there lol) so now the have to backlog the bloodwork which means more waiting for me.

Ill keep posting. Thanks

[Tonny2]

       ojo.        Hello again...my user name is TONNY2, Ronny used to be a member of the forum “ vivir con vih”, we became friends, we even met in person in Mexico before his passing (he died seven years ago, due to non Hodgkin”s lymphoma), my first friend who dies for having aids, since then, I’ve been using his “name” on here, honoring his life.

Well, due to my poor vision, I can’t go back in read the whole thread to find out your problems with your meds history, all I can add is to wish you the best...hugs

[Snowangel]

Stevetool-
Great news on your numbers!

 Is the brain fog lifted with the new meds?  I have never heard of any of them but I don't keep up with the latest anymore.