When to start ART, the research !

[veritas]

This link provides the back=up as to why ART should be started at a cd4 count of 350:

http://www.ncbi.nlm.nih.gov/pubmed/19361855?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_SingleItemSupl.Pubmed_Discovery_RA&linkpos=4&log$=relatedreviews&logdbfrom=pubmed

Don't wait !

v

[CallMeSid]

Thanks for the link.  It's good to read widely on this issue, so one can make an informed decision when the time comes.

I did just want to point out that this meta-analysis was performed on COHORT studies and NOT randomized-controlled trials, so issues of bias do need to be addressed.  (And I have not read the entire article, so maybe the authors do delve into those issues in greater depth.)

Also, do you follow this part of the abstract? 

"We used data from patients followed up in seven of the cohorts in the era before the introduction of combination therapy (1989-95) to estimate distributions of lead times (from the first CD4 cell count measurement in an upper range to the upper threshold of a lower range) and unseen AIDS and death events (occurring before the upper threshold of a lower CD4 cell count range is reached) in the absence of treatment. These estimations were used to impute completed datasets in which lead times and unseen AIDS and death events were added to data for treated patients in deferred therapy groups."

Your thoughts on this methodology and how it may have impacted their findings?

[veritas]

sid,
The methodology used (using co=hort studies), I believe gave enough compelling evidence to come to the authors conclusion. Randomized controlled trials would certainly be definitive, however, that would take years for conclusive evidence. The evidence found in this study, using the patient population as observed (and other studies) was enough to recommend starting ART at a cd4 count of between 350 -450 in the new guidelines.

On a personal note, I started medication in 1991 with a cd4 count of 350. Today they are 1300.

Do you feel that some data being estimated causes such an  anomaly, making it questionable for the authors to come to their conclusion ? I believe the margin of error is minimal.

 I  accept their methodology due to the number of patients studied. A randomized controlled study with a population that large would almost be prohibitive.

v

[CallMeSid]

Cohort studies by themselves can lead to wrong conclusions about medical interventions because the reasons why some subjects do/do not start medication at a given CD4 level is NOT random and the subjects in the two groups differ in ways that can't always be measured.

Forging forward with endorsing treatment based solely upon the findings of cohort studies only (and the marketing departments of pharmaceutical companies and the research/speaking engagements of MDs who accept honorariums from them) has led to problems before (e.g. HRT treatment of pre/peri/postmenopausal women) and the wrong-headed approach was only brought to light when a well-designed RCT was done.

I'm glad to hear of your current CD4 count.  However, I'm betting that the medication(s) you're on now are  not those that you were on in 1991.  Again, I'm glad to hear of your particulars, but it's not really relevant to the discussion of this article.

It's not what I "feel" (or "believe") about the data, it's what I *THINK* about the data.  And their description of using estimates of the distribution of unseen AIDS events and deaths to *IMPUTE*  (i.e. make up!) completed data sets raises my suspicions.  That said, I haven't yet read the full article but will at some point.

Accepting their methodology due to the number of patients studied is frankly, laughable.  A large study with systematic bias and incorrect underlying assumptions may result in tighter confidence intervals around the point estimate(s) for the outcome(s), but it doesn't change the fact that the conclusions are wrong. 

I'm not saying that these conclusions are necessarily wrong (like I said, I have yet to read the full article), but it's NOT, by any stretch, a definitive statement about when to start ARVs.   Personally, I am wary about the new trend to push for starting meds at higher CD4 counts and I don't see strong data coming forth to justify this trend. 

[veritas]

Sid,

Here is the full abstract:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670965/?tool=pubmed

Evidently, they tried to account for the estimated data points by discriminating the data as best they could.
Here is  further non-randomized data:
http://www3.niaid.nih.gov/news/newsreleases/2008/hivHaartStudy.htm

Further evidence in a small controlled study concerning replication capacity with respect to higher or lower cd4 counts at baseline:
CONCLUSIONS: At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.

http://www.ncbi.nlm.nih.gov/pubmed/19194319?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1


I understand your concern with starting meds early. Upon reviewing your numbers , hopefully, you will not have to make that decision for awhile. But, for those in the danger zone now, the guidelines say to start at 350. The evidence is mounting.

v

[CallMeSid]

No.  Actually, you don't understand my concern with starting meds early.  You seem to think I'm concerned about my personal situation only and I'm not.

You seem to see in these studies only what you want to see and you appear to be very willing to trust the methods and interpretations of any paper whose conclusion matches your preconceived notion of what is right ("...by discriminating the data as best they could.")

You keep believin' the hype...

[veritas]

Sid,

The studies are all we have to go by. You seem to be distrustful of everyone and every thing. Having this disease is no walk in the park, however wishing that it didn't happen to oneself is not helpful.

As far as believing the hype is concerned, I've seen too many friends die that believed as you do that there is some giant conspiracy out there to keep those who are positive sick to keep the machine rolling. I don't buy it. The rewards to the researcher that finds the cure are immeasurable and they are all competitive enough to go for it.

As far as "my preconceived notions" are concerned, I know this disease can kill you and trying to find the sweet spot to begin therapy for everyone is daunting. You wait too long you can do irreparable damage to your immune system.   You start too soon you run the risk of AEs from meds ,not to mention the hassle and cost. Guess what, I'll take my chances with the AEs and the hassle before I'd run the risk  of destroying my immune system. You decide for yourself what you want to do.

For what ever your reason is for not  starting meds early, I doubt it's unigue and there is someone on these forums that have experienced the same. Everyone has concerns about starting medications.
Lay the anger down. Look at your decisions logically and make the right one.

I hope they find a cure before you have to disclose your deep down fears to the world.

v

[CallMeSid]

This will be my last comment on your ridiculous thread.  My cat has demonstrated on numerous occasions better logical reasoning than you have here.  I don't have the time and energy to correspond with a zealot fueled by ignorance.

"You seem to be distrustful of everyone and every thing."  NOT TRUE.

"...that believed as you do that there is some giant conspiracy out there..."  I NEVER MENTIONED A "GIANT CONSPIRACY".

"You decide for yourself what you want to do."  ALWAYS HAVE, ALWAYS WILL.

"For what ever [sic] your reason is for not starting meds early...."  UM, TAKE A LOOK AT MY NUMBERS.  DO I HAVE TO EXPLAIN IT ANY FURTHER TO YOU?

"Look at your decisions logically and make the right one."  ALWAYS HAVE, ALWAYS WILL.

"I hope they find a cure before you have to disclose your deep down fears to the world."  LOL!  YOU'RE A MESS.  YOU'RE FAR TOO PATHETIC TO BE ANNOYING.

[georgep77]

you're just being reported CallMeSid   

[Andy Velez]

Sid, the brawling here stops right now. If you have anything further to say just stick to the subject in the thread without any more snarky asides.

Period.

[CallMeSid]

Just curious, Andy:

Why is your charming little note directed to me alone?  Did veritas stick to the subject in the thread and omit all "snarky asides"?

I'll look forward to your reply.

[Andy Velez]

If I had thought his remarks were in the same tone as yours I would have said so, Sid.

We're not going to get into a back and forth about this. Just cut out the nasty remarks or you will very quickly find yourself getting a Time Out.

Give it a rest now and get on to other things.