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ScotCharles
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Reged: 05/06/05
Posts: 924
Loc: Los Angeles
HIV and the brain - update
      #243531 - 12/13/08 08:59 AM

My neurologist at UCLA, Dr. Elyse Singer, has been warning since the mid 1990's that HIV's effect on the brain and nervous systems was a ticking timebomb. The meds never completely eradicate the virus from the body and never effectively cross the blood/brain barrier. A diagnosis of an undetectable viral load means that you have a viral load so low they cannot effectively estimate it, not that you have no virus in your body. Relentlessly, year on year, the virus does its dirty work on the brain and nervous systems.

HIV in the brain causes depression, for instance. Have you not noticed how many people on this site have problems with depression. Some of it is situational depression, that is to say they are depressed because they are HIV+. However, for some the depression is likely organic and caused by the virus.

Interestingly, Dr. Singer has found that HIV effects a part of the brain that processes sensory information, which for me explains why I become panicked or anxious in crowds and on freeways; and, as a result can no longer drive; however, with tranquilizers, I can now go out to movies and go shopping at the mall. The damage done by HIV to this part of the brain also explains why I behave inappropriately in public on occasion, again effectively treated with tranquilizers.

I don't mean to be alarmist, but everyone needs to educate their Infectious disease specialist to this research so that you can receive the medications you need. My symptoms are midway on the way to full blown dementia, but they are treated, for now, with 1000 mg of Depakote, 150 mg of Tofranil, 150 mg of Seroquel, 100 mg of Resperidone and 400 mg of Lyrica. I see my psychiatrist every two months for a tune-up on the meds.

Despite these meds I still have trouble with balance, weakness in my arms and legs, and coordination. None of which can be treated by medications and because of which I am confined to a wheelchair.

Read the following research article that discusses how HIV effects the brain and make certain your IDS knows about this research.

Knowledge is power,

ScotCharles


Researchers identify toehold for HIV's assault on brain

Scientists have unraveled in unprecedented detail the cascade of events that go wrong in brain cells affected by HIV, a virus whose assault on the nervous system continues unabated despite antiviral medications that can keep the virus at bay for years in the rest of the body.

The new research reveals key steps taken in the brain by Tat, a protein that is central to HIV's attack on cells called neurons. Researchers discovered the receptor that Tat uses to attack neurons, and they were able to reverse the effects of Tat in the laboratory by blocking the receptor.

The discovery of a major molecular player in the process opens up a new avenue for researchers to explore in their efforts to prevent or treat HIV's neurological effects, for which there is no currently approved treatment. Researchers say that much of the molecular action that underlies HIV's attack on the brain also occurs in other diseases, such as Parkinson's and Alzheimer's diseases, and that the results spell progress for those conditions as well.

The team from the University of Rochester Medical Center and other institutions published its results online Nov. 13 in the journal PloS One.

The powerful antiviral drugs that keep many HIV patients healthy for years don't completely eradicate the virus from the body, and in the brain, even the very low levels of that remain cause relentless damage. Scientists have observed that a large percentage of HIV patients – perhaps up to half – show evidence of neurologic disease from the virus,

"The current medications give many patients a new lease on life. But the virus is still taking a toll on the brain, even when the virus appears to be much less active elsewhere in the body," said the paper's corresponding author, neurologist Harris "Handy" Gelbard, M.D., Ph.D. of the University of Rochester Medical Center.

Gelbard was a newly minted pediatric neurologist embarking on his career when a good friend of his – a doctor with whom Gelbard had trained – became ill and died of AIDS in less than two years. His friend's struggle, and the severity of his neurological symptoms, touched Gelbard. Gradually, with the support of mentors, Gelbard came to focus on the neurological effects of HIV. He now leads a group of researchers funded by the National Institute of Mental Health that is trying to identify or create the first treatment for the neurological effects of HIV, known collectively as neuroAIDS or HIV dementia.

Scientists have known that Tat, which helps HIV operate, replicate, and infect cells, is at the forefront of HIV's attack on the brain, bringing about severe inflammation. Immune cells within the brain go into overdrive, churning out substances that attract more immune cells, and white blood cells from the body flood in and join the fray, all clumping together to form destructive entities known as multinucleated giant cells.

"Suddenly the brain environment turns from nurturing to toxic, and the brain has to work much harder to send messages. Cells are on overdrive, spending a lot more energy to do the same things they used to do easily," said Gelbard, who is director of the Center for Neural Development and Disease at Rochester.

Other changes occur throughout the brain as well. Neurons that normally reach throughout the brain by forming networks of far-reaching, delicate extensions crucial for cell communication become damaged. Instead of sprouting healthy dendrites – projections that resemble tiny trees – neurons in the brain of an HIV patient have had parts of their dendrites abruptly torn off, in a process known as "synaptic pruning." The dendrites begin to look like a patch of severely damaged trees after a bad ice storm.

Such damage occurs in parts of the brain crucial for thinking, decision-making, and movement and memory. That accounts for symptoms like difficulties concentrating, forgetfulness, poor coordination, confusion, and gait disturbances. In later stages, neuroAIDS can cause outright dementia.

Gelbard's team discovered that Tat works through the ryanodine receptor to sicken neurons in two ways. Scientists have known that Tat makes vulnerable the mitochondria, organelles within neurons and other cells that are commonly considered the "power packs" or energy sources for cells. The team discovered that Tat destroys the ability of mitochondria to protect themselves from changes in levels of calcium.

The scientists discovered another effect of Tat as well. Tat has a dramatic effect on an organelle known as the endoplasmic reticulum, where proteins are actually assembled and folded. Gelbard's team discovered that it's Tat's effects on the ryanodine receptor that cause an "unfolded protein response" seen in the brains of HIV patients. Shape is everything for proteins, and they're nearly always useless or harmful when they are unfolded or misfolded. The problem in HIV patients is exacerbated because protein folding requires a great deal of energy – energy that cells whose mitochondria are petering out aren't likely to have.

The team also showed, in mice, that a single exposure to Tat has long-lasting effects on the brain, causing problems with mitochondria and endoplasmic reticulum weeks later. Perhaps most striking, Gelbard says, is the observation that the exact same types of damage were seen in brain tissue of patients with HIV and neurologic disease but not in tissue from patients with HIV who did not have the neurologic disease.

The findings are in line with past findings from the team, which has shown that the central problem in HIV dementia is not that brain cells simply die. Rather, they become sick and lose their ability to communicate with each other. Because the cells are still alive, there is hope that the condition could be stopped or even reversed with proper treatment. Indeed, doctors commonly see patients who begin antiviral therapy and immediately are less confused and have improved brain functioning, but the effect generally fades as the disease progresses.

In their experiment, Gelbard's team was able to stop the harmful effects of Tat in neurons from mice by using the drug dantrolene, which blocks the ryanodine receptor. While the work offers a new target in the search for a drug that could be used in people to stop the effects of HIV dementia, Gelbard cautions that dantrolene has side effects and would not be appropriate.

"A lot of people are under the impression that HIV has been 'solved,' that somehow, it's no longer a problem. But the disease never went away, and it's a huge problem," said Gelbard, who is professor of Neurology, Pediatrics, and Microbiology and Immunology.

"There are a fair number of similarities between this brain disease and other diseases, such as Parkinson's or Alzheimer's," said Gelbard. "We hope that what we are learning can be applied to other diseases as well."

###

The first author of the paper is former graduate student John P. Norman, Ph.D., now with Exxon-Mobil. Other authors were Seth Perry, Ph.D., research assistant professor of Neurology; graduate students Holly Reynolds and Michelle Kiebala; Sanjay Maggirwar, Ph.D., and Stephen Dewhurst, Ph.D., professors of Microbiology and Immunology; Karen De Mesy Bentley; David Volsky, Ph.D., of Columbia University Medical Center; and Margarita Trejo and Eliezer Masliah, M.D., of the School of Medicine at the University of California at San Diego.



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BrokenWingedBird
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Reged: 11/30/04
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Re: HIV and the brain - update
      #243532 - 12/13/08 10:04 AM

Hi ScotCharles,

Thanks for your post. I think you are the first person that I am communicating with who also knows that HIV is affecting his brain & mind. Thank you for that.

I'm currently wondering about writing an article about my clinic for a national newspaper, without actually naming the actual clinic - because I suspect what I am experiencing at my clinic is going on in lots of clinics worldwide. The doctor who heads my clinic just doesn't want to be involved, he doesn't want to know. He doesn't care about his HIV patients. He dismisses the problems I bring to him. His attitude is that all the problems I have are "par for the course", i.e. part and parcel of having HIV. Bad luck. Tough cheese. The only other people at the clinic are nurses. They do want to know but they too concern me. For example, they want to cheerily go through the motions of taking the blood every three months and weighing me and so forth, but they too don't want to hear about the problems. It's very strange. Maybe they are fatigued with seeing patient after patient with HIV, particularly as many of us are naturally depressed. Maybe they are just protecting their own "good cheer" by putting up a barrier against our miseries. At the same time I often get the feeling that they would prefer it if there was more serious drama going on, i.e. patients not reporting difficult side-effects but actually developing life-threatening conditions again. In other words, I get the feeling they would actually prefer it if we were dying, if the wards were full again. As it is, we are on these cocktails which are keeping us alive and in fairly good health: so, in their view we are going to go on living and living and bringing to them this endless list of side-effects for years to come. At my clinic I almost have to beg for my medicines every three months: they give them to me as if I ought to be extremely grateful. I get the impression that some of the nurses also feel that we should be paying for them - that it is wrong for us to be kept alive with these drugs for free when individuals with other diseases sometimes can't get hold of the drugs they want or have to pay a great deal of money for them, re-mortgaging their homes etc.

This is not a good situation to be in, is it.

You sound like you have a very different clinic. Good.

As for the mental deterioration, let's keep fighting it as best we can. I now have a big sign on my desk saying "Check Carefully!". Not so long ago I didn't need to check so carefully - I checked automatically as I went along. But now I find that things I write often contain "stupid" errors. So it's yet another thing I have had to take on in my life: this extra layer of care with regard to everything I do. It's all a bit of a strain.

Oh to be a 10 year old lad again without a care in the world, and certainly without HIV!

Regards.

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Btony
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Reged: 11/15/08
Posts: 25
Re: HIV and the brain - update
      #243537 - 12/14/08 08:17 PM

Hi Scotcharles. I seem to have more depression issues than I used to since being dianosed. I always dismissed my depression as just a part of my genetic composition (runs in the family so to speak). But I also have noticed that crowds of people in public places (shopping malls especially at Christmas) make me feel paniced and anxious. I have always been a social butterfly and never minded how many people were around me. Now I can ony take them in small doses and feel more comfortable if people I know are around me (strangers unnerve me some). Thanks for the article and the personal insight. I never thought that there might be a connection between me and my status. Something to look into.

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Btony
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Reged: 11/15/08
Posts: 25
Re: HIV and the brain - update
      #243538 - 12/14/08 08:22 PM

I had a similar experience with my first HIV doctor. He just did not seem to care about my downward slide. My test results got worse and he just seemed to say "Don't worry". I changed doctors and what a world of difference it made. My test results are great now. I have had a few great doctors but have to drive a country mile (sometimes over 100 miles one way) just to see them. All in all, I am blessed to be receiving good care now and have health insurance to help cover my care. If possible, try to find another doctor even if you have to travel some to get to them. It makes all the difference and will give you piece of mind. Search the internet for doctors near you or somewhere near you.

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BrokenWingedBird
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Re: HIV and the brain - update
      #243541 - 12/15/08 04:42 AM

Hi Btony. Interesting what you, and ScotCharles, say about reacting differently now to crowds. I'm a bit the same, not greatly, but a bit. With me I think it may not be an effect of the ART drugs but to do with feeling the need to cosset myself, protect myself, look after myself. I used to be very social too and I would be found in all the crowded places, but now I feel the preciousness of time much more and so I want quality environments. Quality environments are environments which also don't impose stress upon me. I find that with carrying this burden of HIV, attending to the daily dosing with rigid discipline, dealing with the continual side-effects, is stress enough. It eats up a lot of the energy that used to allow me to cope with crowded places.

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AIDS2HIV
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Post deleted by Becky
      #243560 - 12/17/08 08:27 AM



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BrokenWingedBird
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Reged: 11/30/04
Posts: 113
Loc: United Kingdom.
Re: HIV and the brain - update
      #243575 - 12/18/08 06:09 AM

AIDS2HIV, thanks for sharing this post from your blog. It is a real reminder of the reality of living with HIV - when the media tries to paint a picture of all being pretty well sorted out now that the ART cocktails are amongst us. This is so not true.

It sounds to me like you have no choice than to stop your meds and let your virus count rise so they can get a sample and test your genotype. I'm no expert in treatment but what I would say is that you should urge your clinic to rest you regularly after you stop your treatment so that they get their sample BEFORE your viral load spirals upwards and CD4 count spirals downwards TOO FAR! Push them on this. Would testing you once a week be ridiculous? Once every two weeks? How about posting a question on this to one of the "The Body's" experts and mark it URGENT. You need expert advice.

Good luck!

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Without a dream, life is a broken-winged bird that cannot fly. Keep hold of your dreams.

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seanboi
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Reged: 12/13/05
Posts: 1
Re: HIV and the brain - update
      #243602 - 12/22/08 04:20 PM

Thanks ScotCharles for your insight. I have seen recently posts like yours on this website and have been meaning to further investigate. I have been diagnosed with Fibromyalgia, (on top of AIDS to now undetectable), but with Fibromyalgia people can get whats termed as 'Fibro-Fog' which is the same that you have described in your post. I have been having and doing the exact things you have experienced. I'm wondering if it's just the Fibromyalgia or HIV or a double whammy I'm going through because it started a few months ago and is coming on fast!
Unfortunately, (as wonderful as he is!), my IDS at Duke, I don't believe, believes the HIV has nothing to do with it. It's been brought up before. So I'm not really sure what to do but to find out as much as possible about this, print it out, and present it to him.
Anyway, again, Thanks for your post!
And good luck to you!
Seanboi

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JerryMc
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Reged: 11/24/07
Posts: 2
Re: HIV and the brain - update
      #243603 - 12/22/08 08:45 PM

Thanks ScotCharles for this post. I was diagnosed with full-blown AIDS in 1990 and was infected in 1986. I am very drug experienced and am now resistant to almost everything except Isentress,Intelence,Fuzeon,Norvir, & Prezista. I have been telling my Dr. for over 3 years that I cannot concentrate well anymore & my short-term memory is horrible. I find it difficult to do simple addition; in Jr. high I was in advanced algebra. I find noisy invironments very difficult. Shopping takes quite a while because I feel like I'm trying to process the items on the shelves and find it difficult to make a decision. My Dr. says if he can get my viral load back down, my confusion should get better. Hmmm? I also notice that my balance is worse; I told my Dr. that I feel like I'm 80! (I'm 42) i do have alot of joint, hip, legs, etc...pain too. I'm also seeing a counseler for depression that has been with me for about 9 mos. now. I hate to be a whiner, but I too think that Drs. are just happy to see a low VL & higher CD4 and mine just shrugs off my complaints with "probably just another side effect" even though I've been on the current regimen for 7 mos.! Anyone else have similar mind issues?

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Jbeil111969
Newbie

Reged: 12/24/08
Posts: 3
Loc: Midwest US
Re: HIV and the brain - update
      #243612 - 12/24/08 07:08 PM

This is closer to where I sit on the mental side of HIV (&AIDs) I've developed an interesting social anxiety over the last few years.
I've known about my HIV status since 1990. As a mother, a wife, I'm expected to tend to certain social details in life. Up until recently I've flit & fluttered around obliviously, living a normal life. As normal as can be anyway.

Lately I drag my heels to avoid ANY AND ALL larger public gatherings. Those I can successfully avoid altogether make me a happy camper. I echo the sentiments of valuing quality time, maintaining a de-stress zone whether in my home or away. All of those self-preservation tactics we tend to incorporate into our lifestyles. KWIM?

I expect the anxiety is related to the number of years I've maintained my good health and paranoia over all the little "bugs" (germs) "out there". I don't want to wreck the system. Some of it is also frustration due to social stigmas living in a smaller community.

My concentration level is decreased. But I thought it was because I have kids and a husband who enjoy driving me nuts (j/k), and maybe a family history of ADD. (undiagnosed, but speculated)

I've tried to self-medicate my mental/emotional/hormonal basket case self with coffee, music, relaxation-breathing techniques, sleep. I also (attempt to) keep my mind healthy(ier) with online games - or games with the family. Word, number, stategy, etc. Reading helps too.



Quote:

Hi Btony. Interesting what you, and ScotCharles, say about reacting differently now to crowds. I'm a bit the same, not greatly, but a bit. With me I think it may not be an effect of the ART drugs but to do with feeling the need to cosset myself, protect myself, look after myself. I used to be very social too and I would be found in all the crowded places, but now I feel the preciousness of time much more and so I want quality environments. Quality environments are environments which also don't impose stress upon me. I find that with carrying this burden of HIV, attending to the daily dosing with rigid discipline, dealing with the continual side-effects, is stress enough. It eats up a lot of the energy that used to allow me to cope with crowded places.




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BrokenWingedBird
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Re: HIV and the brain - update
      #243616 - 12/25/08 05:51 AM

Hi Jbeil,

Good to hear somebody referring to "All of those self-preservation tactics we tend to incorporate into our lifestyles", to all the little "bugs" "out there", and to dealing with social stigma.

I have always been able to perform a number of highly-intricate physical skills, like playing complex piano music, like touch-typing at a rapid rate, like reading difficult material very quickly. All of these things, because of either the HIV and/or the ARVs I'm taking, are now more difficult, they demand greater concentration and attention than before. Now, as they are all very important to me, to who I am and so forth, I have to prepare my mind for them. I find that the ARVs make me feel refrigerated until about 11.30am - it's not until then that I now feel like I used to feel at 8am after a good night's sleep. So I schedule activities which demand concentration for 11.30am and after. But more generally, I am refusing all debris and detritus entrance into my life. I used to let a lot in before, because I had the power to exclude it in a flash and turn my concentration to what I wanted when needed. Now I find moving my concentration from one thing to another quite a challenge. So all the unimportant stuff is being shut out. It's all about maximising quality time. I have been reasonably good with self-discipline in my life but now I need to be a master at it. I need to be much better at saying "No!" For example, a Christmas party one week ago with all the usual eating and drinking left me wrecked for two days. It robbed me of two days of my life really, "but, hey, it's Christmas"! However, I then resolved not to squander any more time in similar fashion this holiday season. I've had two boozy Christmas dinners in the past two weeks and I'm not having any more. The average person could, but I can't because they wipe me out.

The other thing is "depression". HIV specialists are quick to recommend anti-depressants to people with HIV. I don't believe that's the best way to go. I have found that by clearing space for myself, by exercising mental discipline, and by therefore making time for me to do creative things, I can generate enthusiasm and excitement in my life. Occasionally, it even produces moments of happiness and fulfilment. They don't last long, sometimes no more than five minutes, but I have to say that most of the time I am fairly content - and just being content is, I think, a blessing. I'm not dying of hunger and cholera like all those poor people in Robert Mugabe's Zimbabwe!

Festive Greetings to you!


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ScotCharles
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Reged: 05/06/05
Posts: 924
Loc: Los Angeles
Re: HIV and the brain - update
      #243711 - 01/03/09 11:11 AM

I believe someone has been to a psychologist. What you are talking about are non-organic symptoms of a probably organic condition. HIV damages that part of our brain that controls the processing of multiple inputs, the so called Executive Function. Processing input from crowds of people is one thing the Executive function does.

I am not saying that psychotherapy is not necessary for prople with HIV related cognitive dysfunction as the damage to the brain over years of infection has likely led to some dysfunctional behaviors to compensate for the HIV induced brain damage. However, you should also be under the care of a psychiatrist who can presecribe meds to help overcome the effects of the HIV induced damage.

ScotCharles

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ScotCharles
Legend

Reged: 05/06/05
Posts: 924
Loc: Los Angeles
Re: HIV and the brain - update
      #243712 - 01/03/09 11:17 AM

For me, depression is a black cloud that shuts out all light and joy in the world. I cannot lift it with happy thoughts and busy work, rather I spend hours staring at walls unable to move, joyless and without purpose. I never knew how depressed I was until I wasn't depressed anymore. Thank you, Tofranil.

ScotCharles

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BrokenWingedBird
Expert

Reged: 11/30/04
Posts: 113
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Re: HIV and the brain - update
      #243718 - 01/04/09 07:10 AM

Quote:

I believe someone has been to a psychologist. What you are talking about are non-organic symptoms of a probably organic condition.




Hi Scot.

Happy New Year to you. May "Tofranil" keep doing the trick for YOU.

No, I haven't been to a psychologist. Rather, I have a strong medical and psychological background. If you have another look at my posts, you should see that I am talking about a degree of physical mental deterioration that set in about the time when my CD4 count dropped to 200 and which has not departed - despite ARVs getting my count up to a steady 500 with an undetectable virus load.

I believe that people with HIV and this physical mental deterioration we are talking about have two ways of dealing with it: 1. taking drugs which mask the effects of the deterioration, and/or 2. dealing with the situation mentally. Many people, not knowing much about mentally managing themselves, may benefit by acquiring some psychological tools, either from a psychotherapist or from a good self-help book - of which there are many.

My specialist has recommended I take an anti-depressant. However, I have lived through other peoples' experiences of trying different anti-depressants and I don't wish to play the same roulette they have had to - although, in the end, they have each found an effective anti-depressant without bad side-effects. Additionally, for as long as I am able I wish to minmise the amount of toxic drugs I feed into my body. The three ARVs plus occasional sleeping tablets, immodium, and paracetamol is already an unnatural load. Finally, as I say, I know that I am currently able to mentally manage my state of mind - it just takes more discipline, greater will power, and a more bravery on my part than it took before this wretched hi-jacker virus came along and locked itself up in my system!


BWB.


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ScotCharles
Legend

Reged: 05/06/05
Posts: 924
Loc: Los Angeles
Re: HIV and the brain - update
      #243796 - 01/09/09 09:25 AM

I just saw from your post you are in the UK, actually the paracetimol reference clued me in.

I see your point about meds; everyone has a choice to make. For me, I have chosen not to take antiretrovirals until absolutely necessary as the side effects of those meds are intolerable to me.

Tofranil, Seroquel and Respirodone has allowed me to get back out into the world and to begin to learn again how to be a social animal. Without those three meds, I am too panicky to handle large crowds. I begin to imagine conversations and begin to actually hear them. The situation becomes increasingly unmanageable and I retreat into the safe cocoon of mental isolation. This behavior is due, I am told by my doctors, to the damage done to my brain by HIV.

Yes psych drugs are a bit of a crapshoot. Forutnately, I have a psychiatrist who is a dementia expert and I have been able to control my symptoms with relatively low doses of psych meds.

As for the UK, we here in the US may soon have a sort of socialized medicine. I lived in Edinburgh for several years and was covered by the National Health. Whilst I received good care, the care was neither timely nor convenient; however, as you guys say, "We're British, we know how to que."

ScotCharles

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