Crossing the Blood Brain Barrier (BBB). What is it?

[YankInAustralia]

Hi Guys,

I wanted to bring up a topic that I read about from time to time.  Which HIV meds are best at crossing what is called the BBB, or blood brain barrier?

First, when an HIV treatment crosses the BBB, what does that accomplish?  Does that fend off things like HIV dementia?

Second, which meds do that best?

Thanks Guys,


Yank

[Robert]

hi.

I'm on prezista, truvada and norvir for this very reason. My Dr. is an ID specialist and knows her stuff. She is well aware of my memory problems and I think the object is just to try not to make it worse. I see her next month and I'll ask her specifically about the dementia. I haven't asked her before because for some irrational reason I just don't think that's going to be a problem for me. But I can tell you right now since the onset of AIDS and PCP, retention has become a real bitch.

robt

[eric48]

Some people have been diagnosed with a discordant suppresion. Virus suppressed in blood but not in the the brain.

Following a guideline established by letendre, based on a prenetration scoring, they have , apparently been able to balance things. See:

http://www.aidsmeds.com/articles/brain_csf_cognitive_2446_18057.shtml

you can find a score table here:

http://regist2.virology-education.com/2011/5interest/docs/31_Lange.pdf

the table has been amended for adjustments and to include newer drugs, so it is tough to keep up to date. I do not know which is the most recent. Apparently 2010 according to this presentation (p.35)

While high penetrative drugs may be protective, one should also considere that higly penetrative drugs also makes your brains more 'medicated' which may not be so good either.

The score index is a very simplified table.
For example NVP has same score as other drugs such as Zidovudin where as it is much more penetrative

I am on a combo with a scoring of 9 and it drives me crazy. I think we went for an overkill

Hope this helps

Eric

[YankInAustralia]

Thanks for the info guys.  I have to say the presentations are a bit confusing.

It didn't include any info on the newer Integrase inhibitors, like Isentress (raltegravir)?  Do we know how effective they might be?

Thanks in advance.

[buginme2]

Pretty much all  the newer medications are equally effective.

 Why do you ask

[YankInAustralia]

Well I ask quite simply because I want to preserve my brain..  That's all really.

I can't say I totally understand what it all means, I just to make sure I am preserving my brain in the best way possible.

[buginme2]

Well we all want that.

I take it (making an assumption) that since this is your 9th post and based on this type of question your new to being hiv positive and starting meds.  Deciding, which is the best?

Basically all the newer medications are equally good.  Some may be marginally better than others.  The newest medication tivicay (just approved in the US, not sure if it's approved in Europe or Australia yet) seems to have the best efficacy so far (but just by a few percentage points).

If your starting meds and are in a country with access to the newer medications then stick with the new ones and start early.  Some places make you wait to start meds others don't.  You can start immediately in the US and some other places.  Even though there isn't absolute doubt that starting meds early helps, pretty much all evidence points that it does.  So start meds as soon as you can and don't worry about one med being better than another.

[YankInAustralia]

Thanks for that Buginme2,

Well, I am on Truvada and Isentress.  Amazing combo, absolutely no side effects for me at all. I suppose from what I read Tivicay is the new Isentress but as far as it goes for me Isentress is damn good.

I am not new to HIV, I was diagnosed in 2007.  I waited to start meds as my tcells stayed between 700 and a 1000 with my viral load around 10,000, percent about 35%.  Those numbers never budged over 6 years.  That said, in the last few years I've really noticed the campaigns for starting early (in relation to your tcell decline). I started with about 800 tcells earlier this year. 

I learn more all the time about HIV and I suppose I wanted to learn about the BBB.  Cheers for the info! 

[Miss Philicia]

I've had four HIV specialists over 20 years and never had one of them fixate on this blood brain barrier like people on this forum do. Not sure why that is.

[mitch777]

I've had four HIV specialists over 20 years and never had one of them fixate on this blood brain barrier like people on this forum do. Not sure why that is.

My guess is that some people (like myself) have developed more serious CNS and cognitive issues. Was it the meds we took, the virus, the length of time infected, heredity factors? I'm thinking it may be a complex combination of all of the above.

There is a difference, as shown in the link Eric provided, in how affective some meds are with the BBB but it seems they might come with a "catch 22".

While high penetrative drugs may be protective, one should also considere that higly penetrative drugs also makes your brains more 'medicated' which may not be so good either.
 
I am on a combo with a scoring of 9 and it drives me crazy. I think we went for an overkill

My doc is concerned enough about my decline to find out the VL in my spinal fluid and depending on the results, may suggest a med change.

[mitch777]

I've had four HIV specialists over 20 years and never had one of them fixate on this blood brain barrier like people on this forum do. Not sure why that is.

I found this article today which might explain why. It seems that this is pretty recent medical science.

The article is about long-term inflammation within the body and how it affects the CNS. It does not specifically address HIV but does touch on the BBB. Interesting read never the less.

http://www.dana.org/news/features/detail_rop.aspx?id=39464

[eric48]

As I am being treated for depression, I started talking to people around me... It is amazing the number of people who had a bout of it. I thought this was something 'odd', in fact it seems quite common.

back to the original BBB question, Raltegravir + truvada have a scoring of 3+3+1 = 7

I think it is recommended that the CPE score is egal or > to 6 (or is that 7 ? , can't recall)

Most combos , a vast majority, have a NRTI backbone, and where meds availability is less of a problem these are in fact either Truvada (CPE= 3+1=4) or Epzicom (CPE: 3+2=5)

So reaching 6 with the addition of the third molecule is acheved easily in most combos.

I think the problem was identified with people continuing treatment on older combos with a lower CPE score.

Combinaison pills are the latest trend of modern pharmacy and the CPE score is taken into account when designing combinaison.

I guess this is why, when I was treated for mild neuropathy (now gone), I met an expert neurologist who very expressedly said that considering the CPE / BBB thing for treatment decision was pure BS.

I have met people whose neuro impairment is very difficult to notice, but, you notice after a while being around them... It is not only a neurocognitive impairment : these people get socially and economically challenged and THAT really is a problem as it drives them into unemployment/poverty

Hope this helps

eric

[mitch777]

I guess this is why, when I was treated for mild neuropathy (now gone), I met an expert neurologist who very expressedly said that considering the CPE / BBB thing for treatment decision was pure BS.

I have met people whose neuro impairment is very difficult to notice, but, you notice after a while being around them... It is not only a neurocognitive impairment : these people get socially and economically challenged and THAT really is a problem as it drives them into unemployment/poverty

Hope this helps

eric

I'm a bit confused here eric.

I understand your last paragraph and agree that it is an important factor but am wondering if you think the CPE score is BS? (blame it on my cognitive problems. lol. just need a bit of clarification)

I'm on Truvada/Isentress as well and my doc is considering a switch to Epzicom. Earlier this year I was on Atripla. Sustiva was a case of my brain being over medicated for me for well over a decade.

[YankInAustralia]

Thanks Guys,

I really have enjoyed and appreciate this discussion. Sounds like its important to have the right drugs to cross the BBB so as to reduce cognitive effects, but if the drugs are too effective in this regard it can cause issues.

Mitch777, just curious, why are you switching off the Isentress/Truvada?

[mitch777]

Mitch777, just curious, why are you switching off the Isentress/Truvada?

I'm not....yet anyway. After reading this thread I would wonder why myself. He mentioned the possibility if my CSF shows a high VL. Seems like I'm on a pretty effective combo already. Hmm.... will wait to see what he says.

[eric48]

...you think the CPE score is BS...

I take the CPE thing seriously, but the expert neurologist, who was real good and experienced, was highly sceptical, but he did not elaborate

One of the reason for going Epzicom, for me was the prospect of Epzicom+Tivicay (which was in early trial at the time)

I just realized that the author of the pdf I linked to, on page 38 states:

Adjunctive treatments: Psychostimulants, selegiline, valproic acid, lexipafant, calcium channel blocker, memantine, minocycline, lithium, antioxidants, serotonin reuptake inhibitor, nanoparticles do not work

Actually, I have been looking into the use of antioxidants on top of the serotonin reuptake inhibitor I have for depression, and, honnest, I find their use detoxifying. I'll see my doc soon and will inquire about

I really thoughts those antioxydants were for Fashion magazine, but, now I changed my mind. And even if they have a mere placebo effect this is still an effect that I like

Hope this helps

Eric

 

[mitch777]

Thanks eric. Understood. Seems odd that being on Isentress/Truvada that my doc would want to switch out Truvada for Epzicom.