Meds, Mind, Body & Benefits > Questions About Treatment & Side Effects

06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)

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eric48:
So... Why is 'full response' of interest (A) and is there a status even better than 'full responder' (B) ?

A - As per R. Siliciano's above mentioned article: (quote) Eradication efforts will likely be attempted only in patients on HAART who have had sustained suppression of viral replication for years, and therefore the cells responsible for the second phase (+) may not represent a barrier to eradication(/quote)
(+) he refers, here, to residual replication

In other words, any one interrupting treatment at a point on the treatment progression timeline where residual, under the radar, replication has not ceased is bound for... a viral rebound (no pun intended)

Therefore 'full responders' are among the best candidates for the upcoming eradication trials. So anyone willing to participate in an eradication trial should at least be a full responder (or similar). Not convinced? Then browse for eradication clinical trials and look at the inclusion criterias.

And the best way to actively maximize chances to be a full responder:
- long duration of treatment (not under patient's control, recently treated will have to be patient)
- earlier entry into treatment (not so much under patient's control)
- use of Viramune. (a viable option for some patients, but not all...)
(or modern drugs? we do not know yet, since treatment duration is a main key factor)

My point here is certainly NOT to say that NVP is superior to other meds ... I am not interested in dog fights about drugs. I just want to convey to the 'poor' patient who is not eligible for the newest, fancier caviar regimen, and is being scared of this slightly riskier drug, that, on the long run things may turn out much more favorable than expected 

But there is more...

B - on our progress bar, where the 'Pharma-cure' is at the rightmost end, is there any reachable status that is even better than full responder ? Yes there is... The happy few (may not a few as we might think...) are labelled 'secondary controllers'. Ever heard of Secondary controllers ? Most likely not...

These are patients who, generally disregarding medical advise, have interrupted treatment and have had no need (mostly) to resume treatment.
Elite controllers are 'natural controllers'; 'secondary controllers' are patients who were not natural controllers, but who, after years of successful treatment have been rewarded by this 'secondary control' status.

Say, you go by Barré-Sinoussi's definition of a functional cure :
(quote).. (at) least render the need for lifelong anti-retroviral therapy obsolete (/unquote)

quoted from (free) article: Controversies in HIV cure research
http://www.ncbi.nlm.nih.gov/pubmed/22424402

then, it sounds pretty cool...

So, we have this all new video game, where you can raise up from hell, to reasonable health condition, and then move forward to a 'full responder' status then further to that exciting 'secondary control' status, which, from a patient perspective is just wonderfully great. (to date, 5 years off-treatment with clinically good enough control for some patients...)

'Secondary controllers' are a new urban legend ? Is there a clinical trial to back this up ?
Well... I certainly did not make this up !
Skeptical? Then do you own research or just stay tuned for more on that super status and, more interestingly, how it relates to your current or prospective NVP combo and provides more fuel to that interesting Viramune paradox ...

Stay tuned for more

Eric

PS Abacavir users will love the irony of this finding in here:
http://www.ncbi.nlm.nih.gov/pubmed/22994586
Cardiovascular risk factors and carotid intima-media thickness are associated with lower cognitive performance in HIV-infected patients:
... abacavir use was independently associated with a better cognitive performance  ... (no kidding)

eric48:
A very good definition of secondary viral control is given here:

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0037792
Immune and Viral Correlates of “Secondary Viral Control” after Treatment Interruption in Chronically HIV-1 Infected Patients

The work is based on a small, but well monitored, socialized health care cohort of the Institute of Tropical Medicine of Antwerp, including over 1700 patients. This is more a case report than a clinical trial and one could think it is only anecdotal.

Let's grant those doctors in Antwerpen (Belgium) with an ounce of credibility. HIV is their daily turf. There may be some methodological mistakes in the report, but once again, this is from experienced HIV specialists who are not new to this field.

Once striking number is that about 10% of patients (eligible for free treatment) drop out despite medical advise... It blows my mind, I could not believe it. The younger generation has been 'told' about but has never 'seen' AIDS in action, but still...

Among the drop outs 2.5% have been labelled 'secondary controllers' (4 divided by 160)

Obviously anyone just entering treatment has very little chance to control the virus, thus, it would be inappropriate to think that 2.5% of a given cohort are potentially secondary controllers. On the other hand, it is reasonable to think that among the good eggs who did not drop therapy despite many many years of successful treatment, there are some secondary controllers in the closet. Therefore it is not unreasonable to think that in this particular cohort, ca. 5% are secondary controllers.

Is there something special about Antwerpen ? Why other studies have not picked up those SC ?
Are these fakes ? (people telling their doc they are not taking meds while importing generics on the side ?)
(in socialized healthcare where meds are FREE, why would one want to do that ?)
Are there people out there not telling their docs that they have stopped taking the meds (but with good control, the doc can not find out ?)

Well... That is for those doctors to find out...

This is not a denialist thread (by any means), it is about NVP (and ABC/3TC). What does this have to do with NVP ?
Is this topic going completely out of control ? Without access to patients' treatment history, how can we relate to NVP ? Well... why don't we just try to do that... Hack into the Antwerpen cohort SC's medical history and see the intriguing relationship with Nevirapine (Viramune) ?

We will do that on next post.

Stay tuned for more

Eric

Latest Labs:
Oct 15 2012: VL < 20 CD4: 676 (40%); CD8 : 490 (29%) CD4/CD8: : 1.4 (Yeah!!!)
CD4 count well in line with models derived from above mentioned equations. CD4% jumping from 33 to 40 in 2 months is beyond my expectations... CD8 also may need to be confirmed (potential outlier)
Next Labs around Nov. 15

eric48:
Hi,

Nevirapine, the little drug that could:
****************************

Well... We do not really have to hack into people's clinical records...
4 patients have been described and reported as secondary controller.
While my current personal target is full control (as described above), this SC status is very attractive and, IMHO, the closest you can get to a Pharma-cure.
Fortunately, a detailled case report of 2 of the 4 patients can be found here:
Control of viral replication after cessation of HAART
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046910/

Those 4 SC (see above post) are very interesting. They divide into 2 subsets:
Secondary viral control and good immunologic standing (SC+/I+) : 2 patients
SC and less favorable immunologic standing (SC+/I-) : 2 patients

The 2 patients for whom we have treatment information are (SC+/I+) : 1 patient and (SC+/I-) : 1 patient. 3 of the 4 had been on treatment more than 10 years.

Unless I have missed something, here is what adds our final touch to the NVP PARADOX exposed earlier: the 2 patients for whom treatment is known were on ... Viramune!
The studied population is very small and this could be only anecdotal, but, as of today, unless I have missed some other studies, the following seem right to claim:
 
100 % of fully described secondary controller were on nevirapine !...
**************************************************

Considering the usage of NVP is of about 16%, in other words one in six patients, the odds of picking randomly 2 patients in a cohort and find that they are both under NVP is like throwing 2 dice, and get ... a double 6
1 in 36, less than 3 percent. Is this just by chance ?
It can be argued that the numbers are too small to draw a conclusion, yes... but this is intriguing enough.

Still anxious about starting or switching to NVP ? Well, I can understand, but, it is also possibly, one of the best way to get as close as possible to a functional cure

In the next posts, we will see why this might be, and how we can monitor our own treatment progression towards full response and, why not ... SC...

If you would want to learn more about the little molecule that could, I recommend this video

http://us.viramune.com/consumer/viramune/how-viramune-works.jsp 

Stay tuned for more

Eric

Latest Labs:
Nov. 15 2012: VL < 20; CD4: 886 (highest ever) (37%); CD8 : 719 (29%) CD4/CD8: : 1.23 ( > 1 is thus confirmed!)CD4 count NOT in line with my models, but flu shot might be the cause

eric48:
Hi,

Very scarce information has been published to date with the combination of ABC/3TC/NVP
This is why I keep readers of this thread posted about news findings.

For people looking for ressources about this combo, there is actually very little. Which may help explain why this is thread is, as of today, the most read in this section of the forums.

Finally, a scientific poster has been published on this combo...
************************************************************
http://www.jiasociety.org/index.php/jias/article/view/18343
Effectiveness and tolerability of abacavir-lamivudine-nevirapine (ABC/3TC/NVP) in a multicenter cohort of HIV-infected ARV-experienced patients

prospective users may want to review it.

Understanding the Viramune Video
********************************
Last post I linked to a video available on the official Viramune Website.
Actually, in an other post, I had given a simplistic and quite graphic explanation of how NVP works
I am posting here this same description as a supplement to the above mentioned video.
I hope it may help understanding that video, somehow

Variability is due to the infidelity of the reverse transcription process.

The NNRTIS (such as Viramune aka NVP, or Efavirenz aka EFV ) block the reverse transcriptase in a geometrical fashion. (also called steric)

To try to explain in layman's word is kind of difficult.

But think like this.

Visualize a hand holding a baseball, then remove the (large) ball.
You hand now has a shape similar to the reverse transcriptase. keep that shape firm

NVP is a small molecule that will geometrically fit between your thumb and first finger, like a small table tennis ball. When the virus DNA approaches the transcriptase, the small ball gets its way. But in some cases it can manage it way through, but not without damage (mutation)

EFV is a larger molecule (like a tennis ball), it fits between the thumb and second finger, thus better blocking transcription process.

More novel NNRTIs are even bigger and fit between thumb and third or even fourth finger, making a complete blockade. In this respect they are more 'efficient'

only one mutation during a faulty reverse transcription can make the virus resistant to NVP. EFV requires two mutations. In that respect as well EFV may appear more efficient.

Nonetheless, mutations have a cost on the virus, which becomes less fit for the next round of infection. Single round efficiency of EFV is superior to that of NVP. but the infectivity of a virus that may have passed the drug (which is not 100% efficient) is less in case of NVP than in case of EFV

The re-contamination rate is combination of infectivity and efficacy
therefore this combination is similar with NVP than with EFV AS LONG AS the number of rounds and potential events for mutation is not too high (in the case of NVP). IF VL is high or CD4 is high the odds that an unwanted mutation appears increases.

Which is why there is a limitation on NVP initiation on both VL level and CD4 level.
The reason why the cut off value is higher in men than in women is a bit obscure.

It may be related to the fact that proliferation (number of newly created CD4s, hence new 'targets') is higher in women than in men, who, in average have a 100 to 150 higher CD4 count (as observed in the non-HIV infected general population)

The above explanation may have flaws and not scientifically rock solid, but, I hope it helps you...

up-coming posts
***************

In the next posts I'll discuss 2 topics that I have been working on recently:

1- a novel method to evaluate in-vivo drug efficiency. This is some work that I am currently documenting and circulating through research community in order to get it further validated. We hope to publish in a scientific publication. Here, I will only give a layman's approach and outlook of what it implies from the patient perspective

2- a tool to allow users evaluate if they qualify for 'full responder' status, even when they have no access to high resolution VL nor reservoir measurements, as these are out of reach in standard clinical follow up.

I hope this will be of interest to those who found some interest in the Viramune paradox.

The little drug that may be a curse for some and a blessing for others as it may help them get to that secondary controller status, which, from a user perspective, might be just as good as a cure.

Last meeting with Doc
*********************
mix feelings. The cardiologist report had not reached his desk, the CCR5 tropism results had not been provided and we suspect an hospital 'miss'.
That was not a good start. We lost a lot of time looking for these missing reports
Yet, now that I have been put on crestor (rosuvastatin) 5 mg and responding well to it, my lipid profile is a winner:
HDL (the good one) 80 (mg/l)
LDL (the bad one) 90

With such good numbers (CD4 , VL, %, ...), he was quite happy!
Me not. I wanted to discuss a few things, which he was not prepared to hear, and so we ran out of time.
So, I have to redo the CCR5 and go again next month.

Cheers

Eric

friskyguy:
hi eric,

good to hear that joining the small numbers of elite controllers are secondary controllers.

what about the issue of inflammation in both of these groups?

inflammation is the silent killer that wears down our body as the immune system  is continually being on a high state of alert to control the virus.

meds helps us dampen this immune system hyperactivity.

so one might be lucky to be an elite controller/secondary controller and not need meds but if that means that their body is continually in hyperactive mode to control the virus, not sure if that is a good thing for our bodies due to the negative complications to our bodies arising from inflammation?

anyway just throwing it out there.......

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