POZ Community Forums
Main Forums => Living With HIV => Topic started by: Cliff on July 16, 2006, 05:10:42 pm
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A friend told me that they were recently put into a clinical trial for Kaletra Monotherapy. I asked if he was comfortable with the risk he was taking and he said he didn't think that there were any. He specifically asked his doctor if he would have resistance issues and his doctor told him no. The doctor explained that Kaletra was a powerful drug and has been shown to work well on its own. The doctor also explained that the point of the trial was to see if there would be lower side effects from using monotherapy. He seemed to trust his doctor and said, "I don't think my doctor would lie to me."
I think his doctor did lie. I would assume that the main point of a Kaletra monotherapy study is to see if it is effective at maintaining viral suppression, in hopes of saving other drugs and reducing side effects. This is the third person I know who has been put on a monotherapy or a dual therapy trial, who did not completely understand the risk of the trial, (and even believed that there weren't any risks).
This is crap and people really need to push back on their doctors AND do their own research. The cynic in me believes that people are being aggressively pushed into these clinical trials/studies to save the NHS (PCT) money, (drugs paid for by the drug companies and not the NHS), as well as the doctors getting a kick-back from enrolling patients. I hope I'm wrong there, because if so that's unethical.
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The doctor lied and this should be followed up.
Cliff, I think you may be spot on re: pushy researchdocs, although the reason is prob. less PCT motivated and more to do with keeping the research funds flowing in for a "leading" clinical centre.
On the basis of the few studies to date, Kaletra monotherapy may be a fair choice if the patient expresses a preference and has been duly cautioned re: its experimental nature, or as a least worst option for people with poor adherence where the risk of resistance is less on just Kaletra (rather than on a combo with nukes in it taken badly), or perhaps as a least worst option for reasons of toxicity/allergy.
This is a real issue and makes me fume.
- matt
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This is another instance that shows how dangerous it can be to surrender your health care to your doctor. Before making any changes to your meds or before going into a trial you have to do your own research. We like the idea of trusting our doctors, but they are not all-knowing, and sometimes what they tell you as fact is really just their opinion.
Allan
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I've met more incompetent, under-informed doctors than you can shake a stick at. Being mildly skeptical always, and doing your own research is great. But getting others to feel that way -- that doctors are not infallible deities, that more knowledge is almost always a good thing -- can be/is hard. Lots of frustrating examples. Easier to trust the doc. Most of the poz men I know seem to know surprisingly little about HIV/AIDS; one twenty-year-old college student just about seemed to grasp that a higher CD4 count and percentage were good things; completely reliant on whatever the doctor and nurse say. And of course I'm not talking doing "research" as in reading scientific articles in professional/academic journals; just a little basic Internet reading would be nice.
I suppose that's true of most diseases, though: the proportion of people who actively try to find out as much as they can about the disease, in relation to the number of people who passively accept the whitecoat advice and verdict, is pretty small. Maybe I'm wrong about this wrt to HIV, but judging solely by my interactions with other positive gay men over the last year, I would think not.
Jay
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I think the best way to resolve this issue is to go back to the study protocol and the informed consent that was signed by the patient before participating in the study. If that risk is specifically stated in the informed consent and he was told no, it would not happen, then he needs to go back and revisit this discussion with his doc. It's true that there are always potential conflicts of interests when enrolling patients in clinical trials. But we are not hearing the full account of the details here from both sides. Incidentally, Kaletra monotherapy studies have consistently shown no development of PI resistance in patients who failed treatment (i.e., developed virologic rebound while on Kaletra alone). This is a little bit mysterious and no one has yet been able to provide explanations for such. Those who developed virologic rebound fortunately achieved viral suppression again by adding NRTIs to the regimen (Link to January 2006 Hopkins HIV report, page 6 (http://hopkins-aids.edu/publications/report/nl_06_jan.pdf)). This is not to say that docs should be cavalier in declaring that "resistance to Kaletra would not happen with monotherapy" and I would be very surprised if this "risk" is not spelled out in the informed consent for the study. But that would be a good place to start to try to resolve this.
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Gerry is right about the informed consent document, which does lay out the risks of participating in a trial or study. However, as someone who has participated in more than a dozen trials over the years, I can tell you that patients are not encouraged to read these documents. They often consist of ten or more pages written in fairly legalistic language. Usually the research nurse lays the the document on the table and immediately turns to all the pages where you have to sign or initial. It's like the fine print document that pops up on your computer screen before you can install new software. (Does anyone ever read that stuff?)
I always find out enough about the trial before I'm presented with the informed consent document, so that I know what I'm in for. And before I take the first pill, I do read the document in detail. However, my bet is that most people do not do this and simply trust that no one in their doctor's office would ever ask them to do something that might not benefit them or, worse, could possibly harm them.
Allan
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I'm certain the risk were spelled out in the informed consent pages. That way the drug companies and doctors can stand behind that form should something go wrong. However, it's quite easy to 1) not fully read the informed consent (either through patient neglect or being rushed by the administrators) and 2) have verbal representations from your doctor which contradicts or downplays the risk.
None of the people I know were unhappy with being in the trial and thus had no reason to try and blame the doctor for anything. However, they all didn't understand what they were getting into and they all relied on the trust that their doctor was looking out for their best interests.
To me, it's not just a matter of informing people of the risk. You need to make sure they completely understand them. If at the end of the day, a patient is put into a study and that person doesn't fully understand the risk, (whether through inadequate disclosure on the part of the administrators or a lack of understanding on the part of the patient), then the doctor is negligent (in my opinion). The doctor has the knowledge, the experience, the educational background, access to requisite information and most importantly the trust of the patient. They should have a higher burden of care, than simply making a patient sign a form without checking to see if the patient truly understands and agrees to the risk.
- Cliff
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I'm not disagreeing with you, Cliff, except perhaps the part where you assign negligence. What I'm saying is if your friend wants to resolve this issue now, he needs to go back to the informed consent and discuss the discrepancies between what he understood his doctor told him and what was spelled out on paper.
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All I can say being on STUDY, is I am glad I dont have his ID Doc! :o
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I'm not disagreeing with you, Cliff, except perhaps the part where you assign negligence. What I'm saying is if your friend wants to resolve this issue now, he needs to go back to the informed consent and discuss the discrepancies between what he understood his doctor told him and what was spelled out on paper.
You're right. But sadly, he won't (at least I assume he won't). The trust of a doctor (or the ability to keep ones head in the sand) is too strong. In that sense, I understand your point (in terms of negligence). It is his responsibility, (as much as it is the doctor), to understand what he's getting into. It's just so sad, (and frustrating as hell), to see this kind of stuff happen. Chances are things will be fine (i.e., resistance wise). Hopefully.
I think Allan has a thread about taking responsibility for your healthcare. This is so true.
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I think the risk of putting people onto unproven / drug therapy far outweighs the benefits. Personally, I am nobodys Guinea Pig, one only has to look at supposed 'safe' new generation arthritis drugs such as Celebrex, that were withdrawn after extensive 'testing on human Guinea Pigs' . Anyone who takes the risk of unproven drug therapy does so at their own 'sometimes considerable risk'.
It should be the doctors prescribing these 'unproven drugs' that have the responsibility for making absolutely sure patients are fully aware of the risks of taking non approved drugs. I fear all to often patients are ill informed themselves & delegate responsibility for what are serious judgement calls to over enthusiastic doctors.
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I am on a Pfizer Maraviroc study. Did my Doctor encourage me to particpate? Yes, he did. Did I review the consent document, and any other onlike information I could find on it? Yes, I did.
The reason I decided to participate was that I thought: Ok, I need to be on meds anyways. I assume that the drug companies would like to at least try to come up with something better than is already out there. I am well monitored and have always known that I can opt out at any time.
Part of me also wanted to do my little part in helping the research. If we in the HIV community will not participate, then who will and how will they assess the short term and long term effects of new drugs? When I described some issues I was having with fatigue, my Doctor immediately suggested a switch to Tenofivir from AZT.
Of course, I am not 100% sure that I am getting the study drug. Doctors are human, some will be wonderful, some will be awful. I had a GP that for 6 years could not figure out that I had HIV and gave me 3 different diagnosis.
I have now been in this study for 1 year, I feel pretty good and my labs and all healt factors are great.
Naftali
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Cliff, great post on a very interesting subject. My wife died in 1999. It is of the opinion of several DRs that her liver failed due to the drugs she was taking when we sneeked off to the NIH in D.C. This was 1996, and her viral load was at 200,000, so we had little choice.
Your post raises a very important point. We should all think LONG AND HARD before just joining a trial study. take it from me: It is indeed a matter of life or death. I would remind everyone that the drug companies have a huge influence in all aspects of health care. I would highly suggest that if you do decide to do a study...research it and do your due dilligence. Just because your DR says its ok...it may not be. God knows what goes on behind closed doors with all parties involved.
I'll leave you with a most memorable quote which haunts me to this day: "The drugs we're giving you could very well kill you" the nih dr said. I want to puke right now.
Thanks Cliff for shedding light on a very important subject.
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Resistance implications of monotherapy with lopinavir/r (Kaletra) (http://www.i-base.info/htb/v7/htb7-7-8/Resistance.html) - i-Base report from the recent resistance workshop in Stiges.
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Resistance results were presented from two randomised studies of patients who failed on lopinavir/r (Kaletra) monotherapy.
The MONARK study randomised 136 treatment naive patients with baseline viral load <100,000 copies/mL to either lopinavir/r monotherapy (n=83) or lopinavir/r+AZT+3TC (n=53), with follow-up for 96 weeks.
Mean duration of follow up for this analysis was 64 weeks (range 48-96 weeks). Resistance testing was performed following rebound >500 copies/mL after achieving <50 copies/mL, or >1 log from nadir of <400 copies/mL, or after study discontinuation.
A significantly greater percentage of patients receiving monotherapy had viral rebound or poor suppression, therefore qualifying for resistance testing: 21/83 vs 3/53 (25% vs 6%). In the monotherapy arm, two patients showed protease mutation changes from their baseline sequence: one showed M46I on viral rebound at week 40, and the second developed L10F/L and V82A/V mixtures at week 72 after extended duration of low-level viraemia (VL <500 copies/mL). One patient in the 3-drug arm developed M184V resistance to 3TC, but with no change in protease.
The authors emphasised that resistance to lopinaivr/r when used in 3-drug regimens is very rare (ie no cases out of 654 patients in 4 registrational trials and only a single case report has been published), but that other case reports of development of PI resistance mutations have been reported from monotherapy studies. They concluded that the barrier for the selection of PI resistance with LPV/r monotherapy may be lower than with lopinavir/r-based 3-drug regimens.
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Etc...
- matt
(The doctor was wrong to say "none", mr)
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Cliff, I was put on Kaletra monotherapy. Only lasted a couple of months before VL started climb. They told me they were having a lot of success with it. I really had no choice cause at that time I was resistant to everything else.
Is your Friends Dr. the same as mine?
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I have been on 4 trials- Crixivan, T-20 (Fuzeon), TMC-114 (Prezista) and now on GS-9137 (non-drug arm of study until Oct). I have a pan-resistant virus, and am allergic to many drugs. For me, there have not been a lot of options.
I believe that the patient has a responsibility in protecting themselves- research, reading journals, getting second opinions, and absolutely reading, and understanding every word of the informed consent.
One also has to weigh the side effects (one of which can be death) of the drug, with the risk of not taking the meds or taking other meds. It is a very difficult thing to deal with. You are given few choice- possible fatal side effects with the trial drugs, or possible illness and death with drugs that one has resistance to, or the possibility that this drug will work well to keep the vl down, and the t-cells moving up.
If there is any question that the doctor is not acting in the best interest of the patient, the patient needs to stand up and question the doctor, change doctors if necessary.
Are some doctors on a glory path, and pushing research to benefit themselves? I have no doubt. I felt my first ID doctor was like that, and I switched doctors pretty quickly. He was not a bad man, he just had ambitions other than his patients, or at least that was how I felt. By the way he is now Chair of the Dept...
Bottom line for me is that a patient has to educate themselves, and not blindly follow orders. I never go to any appointment without all my info, medication list, allergies, discharge papers from the hospital, info I have found and have questions on....
Hope that answers the question, I sort of started to ramble....
Christine