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This Month in HIV: A Podcast of Critical News in HIV

This Month in HIV: Top 10 HIV/AIDS Stories of the Past Year

May 2008

This podcast is a part of the series This Month in HIV. To subscribe to this series, click here.

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Heart Attack and HIV Meds: Not a Black-and-White Issue

On to number three.

Number three has to do with an ongoing concern regarding the side effects of HIV medicines, particularly the cardiovascular effects. There was a really important paper published in the New England Journal of Medicine by the D:A:D group.15 The D:A:D study is a large, metacohort study, meaning that it's a collection of different large studies all pooled together. It's pretty powerful; over 30,000 people are enrolled in this study currently. What the researchers are able to do with that kind of data is look for trends that occur during HIV therapy. One thing they've been able to do is look at the risk of heart attack, and the rates of heart attack.


In this analysis, which was published at the end of 2007, what the researchers found was that there were about 350 or so heart attacks in the group of patients that they had -- about 23,000 at the time of this analysis. They were looking at what the risk factors were that led to individuals having a heart attack. One of the things they looked at was a patient's exposure to HIV therapy. They've shown that over time, as you're on combination HIV therapy, your risk of heart attack increases incrementally.

What the researchers were able to also do is tease out which type of HIV therapy might have this effect, and they found that protease inhibitor therapy was associated with this increased risk of myocardial infarction. Whereas the non-nucleosides, like Sustiva and Viramune, were not.

This is kind of controversial and we'll have to think more about this over time as more data come in. But what they were able to show is a pretty clear signal for protease inhibitors.

The non-nucleosides, like Sustiva and Viramune, did not have as clear a signal. It was a little bit of a wiggle line; it went up and then it went down a little bit. So, it was not as clear. Part of the reason for that is that there are not as many people on those drugs in this cohort -- this cohort is mostly European, with some North American patients included. For protease inhibitors, which were much more popular in this group of people, there was a clear trend that was significant.

The bad news is that protease inhibitors seem to increase your risk of heart attack. The good news is that the risk of heart attack in this study was really low. As I said, we're talking about 350 heart attacks among 23,000 people. Not tremendous numbers, and it's important to remember that not every single one of those heart attacks was due to medicines. If you followed 23,000 people without HIV, there would be some number of heart attacks. Some of these were inevitable; some were influenced by HIV; some were influenced by HIV medicines.

Other important data have shown us that if you're not on HIV medicines -- for example, if you are someone who started on HIV medicines and then stopped taking them -- your risk of cardiovascular disease goes up.16

That is, stopping HIV medicine, allowing your virus to go kablooey, and all the subsequent inflammatory changes and things your body has to do to deal with the virus are really bad for your heart.

Overall, protease inhibitors probably increase the risk somewhat of a heart attack, but it's better than being off HIV medicines. I think this is an important study that helps us quantify the risk, but also reassures us, because at least during the time period of the study (about seven years) heart attacks were fairly rare.

The researchers never did tease out how many of the people in this study were smoking cigarettes, for instance.

"We know that uncontrolled virus puts a strain on the body in many ways, leading to more problems with liver disease, leading to more problems with heart attacks, and leading to more problems with kidney disease. The virus itself is probably worse than anything else."

Right. So there are other risk factors, and they try to correct for them. The other thing that they don't really do a great job of is telling us, in the people who got heart attacks and were on protease inhibitors, were the protease inhibitors working? Did the people have uncontrolled virus [i.e., a high viral load]? We know that uncontrolled virus puts a strain on the body in many ways, leading to more problems with liver disease, leading to more problems with heart attacks, and leading to more problems with kidney disease. The virus itself is probably worse than anything else. Protease inhibitors are making a rare event a little bit less rare, but that is better than not being on protease inhibitors.

What would you say to a 25-year-old person living with HIV, who's worried by this kind of study and who's on a protease inhibitor? What can he or she do?

I think the most important thing is to understand that the magnitude of the change of risk in heart attacks with protease inhibitors was a fraction, really, of what you get with smoking or with uncontrolled high blood pressure -- those are the things that we can change.

In this group of patients, about 60 percent smoke.17 That's an incredible amount -- and we see this consistently in HIV-positive people!

When you look at Americans and Europeans with HIV infection, the Americans smoke like Europeans. It's incredible! HIV-infected people smoke like French people do.

In comparison, in the general population of the United States, only 21 percent of people smoke,18 so we see that smoking is very prevalent in patients with HIV.

What we should do, rather than mess with their HIV medicines, is:

  • Get people to stop smoking.
  • Get them to control their blood pressure.
  • Get them to exercise more.
"We need to take care of the usual, traditional things when we think about risk for cardiovascular disease. I think HIV medicines are secondary in that respect."

These are things people should be motivated to do if they want to survive. I think this is important, but it really puts this into perspective. We need to take care of the usual, traditional things when we think about risk for cardiovascular disease. I think HIV medicines are secondary in that respect. So I'd tell that young person, "Your risk is pretty darned low because you're young. You've got to stop smoking because you're aggravating your risk and we want to see you be here for a really long time. I wouldn't worry so much about your medicines; we can handle it."

Would you say something similar to someone who's 45, doesn't smoke, and doesn't have genetic risk factors, but is on a protease inhibitor? Is there a greater worry for that person?

I think there is greater worry the more risk factors someone has that you can't control -- such as a family history of early heart attacks, under 55 for a close male relative and under 65 for a close female relative; a history of blood pressure problems, even though it's controlled right now; and diabetes.

People who've done everything they can to control their risk factors, but have these immutable, unchangeable risk factors, including genetics, are the people for whom you really try not to put another straw on the camel's back. It's one of the factors that you have to weigh when deciding what HIV medicines to be on.

In this particular study, it looks like protease inhibitors are worse than non-nucleosides, but it's going to take a little bit more time to make sure that's actually so. If it is, then yes, given the data we have now -- yes, that may gravitate the clinician and the patient to think, let's stay away from protease inhibitors.

When we look at lipids, there's not as much of a difference between protease inhibitors and Sustiva as we once thought there was. It's not all about cholesterol; there's something else going on here. So yes: It's one important factor. For someone with very few risk factors, for me, it's not a big deal; it's not a big factor.

So really, the answer is that it depends on who you are, and what your story is.

I think these data are important in light of recent data from the same study group, looking at Ziagen [abacavir; this drug is also contained in Epzicom (abacavir/3TC, Kivexa)]. The data suggested that Ziagen -- and Videx [didanosine, ddI] -- also increased the risk of heart attack.19 It's the same sort of story. I think we have to look closely at the patients we're seeing, their risk for cardiovascular disease, and weigh the benefits from this particular study of giving a drug or not giving a drug.

Defying Expectations: Kaletra, Sustiva and Body Fat

On to number four.

Number four follows a similar vein; it looks at a different metabolic complication of HIV medication, and that's body shape, with some hint of lipids here, too. It was a really, really important HIV study that we in the HIV field got very excited about, because it was done not by a drug company; it was done by the federal government here in the United States, and it was done across the country.19

It really was a nice representative study of treatment for people who'd never been on HIV therapy before. The study was done by the ACTG, and that stands for AIDS Clinical Trials Group. AIDS Clinical Trials Group is a federally-funded network of study centers across the country. This study is called ACTG 5142. The ACTG numbers their studies; they don't have cute little acronyms or abbreviations.

This study pitted Kaletra [lopinavir/ritonavir], a protease inhibitor that's very popular for initial therapy, against Sustiva. People could take either one of these drugs plus two nukes [nucleoside reverse transcriptase inhibitors], like Retrovir [zidovudine, AZT; this drug is also part of Combivir (AZT/3TC)], Epivir [lamivudine, 3TC; this drug is also a part of Combivir], Zerit [stavudine, d4T] or Viread [tenofovir; this drug is also a part of Truvada (tenofovir/FTC)] -- commonly used drugs. There was a third arm in which people didn't use any of those nukes, but just took Kaletra and Sustiva together.

The real important data, for our purposes, was the comparison of the people who took Kaletra with two nukes with the people who took Sustiva with two nukes. We had assumed that the Kaletra was going to lead to more body shape changes and higher cholesterol and all that stuff. But that turned out not to be the case.

In a rigorous study of a large number of people -- 700 people -- what we found was that the differences between these two drugs was not that stark when it came to big bellies. Both drugs made people's bellies increase in size. Both drugs led to increases in cholesterol -- not only the good cholesterol (HDL cholesterol), but also the bad cholesterol (LDL cholesterol).

Importantly, triglycerides were a little bit higher with the Kaletra than the Sustiva, and that's been shown in other types of studies as well. Not a big surprise there. The surprise was that cholesterol was not a big deal; also, bellies were not a big deal.

What also was a big surprise was, when we looked at limb fat -- that's fat on the arms and legs -- that's where we saw a difference. Surprisingly, it was against the Sustiva. People who took Sustiva, regardless of what other medicines they were taking in their HIV regimens, had more wasting of fat in their arms and legs than people on the Kaletra.

"These results totally blew people away. ... It opened up our eyes that we have to think anew about body shape changes, that it's not a protease inhibitor thing. In fact, if anything, the protease inhibitor was associated with protection against fat wasting of the arms and legs."

These results totally blew people away; these were completely unexpected results for most people in the know, who are really interested in this. It opened up our eyes that we have to think anew about body shape changes, that it's not a protease inhibitor thing. In fact, if anything, the protease inhibitor was associated with protection against fat wasting of the arms and legs.

There was no data about fat wasting of the face included in the study. These were all objective measures using scans of the body, so we don't have any important data yet about facial fat wasting. What we do see is that fat wasting of the arms and legs, which generally correlates with fat loss elsewhere, was worse with Sustiva.

With Truvada and Sustiva [this is the combination of drugs in Atripla], the risk was pretty darn low. It was higher than if you took those two nucleosides with Kaletra, but the good news is for people who are on Atripla, the risk of having significant wasting of fat in the arms and legs was fairly low and uncommon. I feel somewhat reassured in giving people that combination. The problem was more when you took Retrovir or Zerit along with Sustiva; then you saw unacceptable rates of fat wasting.

It was a really important study that helped debunk some of the myths we've had even in the absence of data about what these medications do to body shape and to lipids. I think that's important and that's what research is about.

But this is just a clue about some of the body shape changes that happen with these drugs. Isn't it true that we still don't know how to treat those problems and we don't completely understand them?

No, in fact, a lot of people after this felt like we had to just throw away everything we understood about fat wasting. If anything, people are thinking that maybe it's not so much that the Sustiva causes fat wasting, but that the Kaletra protected against fat wasting. There may be suggestions from other studies that that may be the case -- that there's something with protease inhibitors, ironically, that protects against fat wasting.

I think you're right that this really makes us have to think outside the box about this. It says nothing about treatment, but it may say something about prevention.

It may be that we're understanding that, if you want to avoid fat wasting, you shouldn't use Retrovir; that Viread would be a better drug than Retrovir. That's important information for people to think about when starting medicines. It depends how big a deal this is to you. There are people I see who say, "I'll take anything, but I don't want to look bad." I steer them away from those regimens that were associated with fat wasting in this particular study.

Which would be?

Sustiva with Retrovir and Epivir. Certainly Zerit, which we don't use anymore. I wouldn't even use Combivir with Kaletra.

I would prefer to use alternative nucleosides. In this case, Viread looked really good. Ziagen was not studied in this study, and there are other issues with Ziagen that are emerging.19,20 Right now, there's a limited choice as far as nucleosides for people who are concerned about this complication, so you just have to pick from that short list. When body shape is a major issue, we've got to look at the data and we shouldn't just rely upon assumptions or perceptions.

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Copyright © 2008 Body Health Resources Corporation. All rights reserved. Podcast disclaimer.

This podcast is a part of the series This Month in HIV. To subscribe to this series, click here.


This article was provided by TheBody. It is a part of the publication This Month in HIV.

Reader Comments:

Comment by: William (London, UK) Wed., Jan. 13, 2010 at 5:38 am UTC
My name is williams, I am 35 years old male from London, UK.
I do not have HIV but i am very sad to learn that many people are dying of this disease. I can help or support someone who have this disease in any way that I could. I can also be your best friend or even lover.......
I am looking for good friends from all over the world. It doesnt matter if you have HIV or not.
I am a good Christian and do not care about age, race, color or religion as we are made by the same God...
I HATE Lies, injustice, terrorism and discrimination..
If you wanna be my friend send me an email with the subject: FRIENDSHIP.
Peace and Love to you all..
This is my email address:
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Comment by: Sima (Dsm) Sat., Jan. 24, 2009 at 11:00 am UTC
Thanx for the wonderfull web site.i now know where to get different information about AIDS/HIV.
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Comment by: Priscillar (South Africa, Johannesburg) Thu., Nov. 20, 2008 at 10:49 am UTC
I was diagnosed last year, 2007, with a CD4 of 59. Now I am at 550, taking Truvada and Stoctrin. What are my chances of opportunistic diseases, and toxicities? I need to be linked with a friend in SA.
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Comment by: azazhu (Ethiopia) Tue., Oct. 7, 2008 at 10:06 am UTC
that is very itnteresting
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Comment by: jim (alaska) Tue., Oct. 7, 2008 at 2:12 am UTC
i get the body regularly in e-mail and I am so thankful to all the wonderful doctors that contibute. I found out I had AIDS when I was hospitalised in 2000 with pml encephalitis and thank god for great doctors and great medicines i am alive to write this and i am am doing quite well. my past doctors whom i have kept n contact with in oregon are amazed. i was paralyzed on the right side of my body and they told my mother i would not survive the week. now i am a truck driver driving big semi's! People, get tested. If applicable, get on meds and PLEASE do not miss any doses. i say this from the bottom of my heart! You can e-mail me at have a wonderful life! GET TESTED!!!!! Thank you again wonderful doctors!!!!!!!
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Comment by: caco (florida) Mon., Sep. 22, 2008 at 11:11 am UTC
Will we ever find a cure for HIV?
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Comment by: runing.outof.time (vaal) Wed., Sep. 10, 2008 at 7:22 am UTC
we r dieying. where or when is the cure
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Comment by: simone (Rosebud,SD) Tue., Sep. 2, 2008 at 12:42 pm UTC
I'm working to get the Native American people to get tested on the Reservation we have no testing. I'm working to collaborate with IHS to start testing I'm with the CHR Program. The hardest part is trying to get the people to get tested. I'm going to do the best I can to get them tested. I just wanted to let people know that their is a problem getting people tested everywhere.
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Comment by: lashawna Mon., Aug. 11, 2008 at 8:46 pm UTC
i think people really need to understand what sex is. too many people think it's ok to have unprotected sex when it is not ok. if you are going to do something with someone, wrap it up please. be the smarter person. that goes for straight people and gay people. get it together people! life is too short, please do not make it shorter.
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Comment by: jerry morales Thu., Jul. 31, 2008 at 1:33 pm UTC
I have a comment for dissidence 101, you weren't to concerened about vaccine success when you became infected and these drugs do seem to be keeping me alive. So bravo for the new drugs. I'm on Prezista and Isentress and celebrate their arrival. I'm sorry life doesn't seem as rosey for you.
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Comment by: Casey Fri., Jul. 18, 2008 at 12:14 pm UTC
I was wondering if you knew where to find information on how to join a certain study group of individuals with HIV+ in their states?
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Comment by: Innocent Fri., Jul. 11, 2008 at 9:10 am UTC
I have recently been diagnosed HIV+ but now i have hope that i can live longer but i've got a problem with FLU & Tonsils
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Comment by: Jason Mon., Jul. 7, 2008 at 7:16 pm UTC
I read that CDC predicts that if someone is positive less than four months that they can eliminate the virus from the body (with meds) within an average of 7.7 years. Is this true?
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Comment by: rami Mon., Jul. 7, 2008 at 3:28 pm UTC
Thank you very much for this energy you are putting into these podcasts / reviews. i find this so importnat. this gives much hope and info. Thank you!
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Comment by: wam Sat., Jul. 5, 2008 at 12:49 pm UTC
Hi Ezekiel Otieno where are you in Kenya. I am also positive living in U.K detected about 9 mths ago single mum of three. You can email me at
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Comment by: Gideon Lawal Mon., Jun. 30, 2008 at 9:34 am UTC
Well am kinda new to this well. i lost my brother to this disease. right now the last time i check my status i was positive too and then my cd4 count is 375 and am still on oi. i need a friend from Europe and USA and anywhere in the world to help pass through this hard time right now am having stomach pain and headache.. here is my email:

Hope to hear from you soon
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Comment by: mickery Sun., Jun. 29, 2008 at 2:06 pm UTC
That's a great interview that everyone (whether positive or negative) should read.
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Comment by: dorcas Thu., Jun. 26, 2008 at 8:28 am UTC
doc.a big well done 4 d goes a long way to give hope and encouragement to all the infected.its a is a fundamental right and not a disease that needs to be adhered to.thanks
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Comment by: abdalla Tue., Jun. 24, 2008 at 3:21 am UTC
very exciting!
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Comment by: Robert Tue., Jun. 3, 2008 at 1:42 pm UTC
Dear Drs. at "The Body"

Keep up the good work! As you say all the time, there are great drugs out there but prevention is key!

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Comment by: bruno Sun., Jun. 1, 2008 at 8:40 pm UTC
god bless us all. stay strong people.
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Comment by: jason Sat., May. 31, 2008 at 10:33 am UTC
are there some of those drugs here in the philippines and how much its cost?
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Comment by: hilary Wed., May. 28, 2008 at 6:30 pm UTC
i have just found out my wonderfull nephew is HIV. Am so upset, my world has came crashing down. Thank God i can read positive stories. i can only pray he will outlive me. This happens to other familes not mine or so i thought. feel so ashamed. i thought HIV was AIDS I'm learning, however we all pretend it is not happening. i pray for a cure.
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Comment by: araceli villafania Tue., May. 27, 2008 at 2:07 pm UTC
very good info
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Comment by: TEDDY Thu., May. 15, 2008 at 9:05 pm UTC
Good job, but we need drugs that you could take once a month,any possibility? I know the pharmaceutical companies will frown over this as it will make volumes on profitable
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Comment by: johnk Wed., May. 14, 2008 at 12:55 am UTC
What a smart, sharp overview! I too think the plethora of new interesting drugs is the story of the year. They have given me lots of hope as I've undetectable for the first time in 15 years! HIV medicine has made such strides. I'm one lucky man!
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Comment by: John morse Sun., May. 11, 2008 at 10:42 pm UTC
I was diagnosed with HiV at age 70! I am currently enrolled in a trail 96 week study for HIV naieve people. I am taking MK-0518 (or Placebo) Efavirenz (or placebo) and Truvada. within three months of taking the medications My viral load was undetectable and CD was up to 415 from 275! I have been on this program for a year now.
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Comment by: dissidence101 Sun., May. 11, 2008 at 10:22 pm UTC
That's just simply amazing that the biggest story of the whole year is "THERE'S MORE DRUGS". Gezze. I have a better one. How about and to the dismay of researchers, Merck's v520 complete and utter vaccine trial failure?
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Comment by: Noni Sat., May. 10, 2008 at 3:20 pm UTC
I started treatment in 2003 with CD4 of 8.I was on d4t, 3tc. I experienced loss of fats in hips and butt and changed to azt. Problem is i always worry about what if it doesnt work because in S.A we have only limited (2) regimens available. Are we S.A allowed to have or access these plenty of meds available in U.S.A and other countries? If so how do you access them?

Worried in South Africa
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Comment by: ezekiel otieno Sat., May. 10, 2008 at 9:10 am UTC
this website has given me a lot of strength.Through this I've learnt that i can live long enough than the seven years since i knew my status and i'm not alone.
I'm requesting this website to connect me one person living positively in Europe or Asia. I am from Kenya.
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Comment by: Carole Ricks Wed., May. 7, 2008 at 7:45 pm UTC
Hello Everyone;

I would like to say how happy I am for all that have found their meds to work and they are doing great, Thank God for that, because He is always looking out for us all the time. I lost my brother to Hiv/Aids last year because he didn't and wouldn't seek treatment until it was too late. I miss him very much and I also have another brother who is Hiv positive as well. He is keeping up with his doctor's visits and taking care of himself. Please know that there are programs out there that can help you if you are sick. Don't wait! Seek help right away and remember that knowledge is power. God bless you all.
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Comment by: Dr. Elizabeth Mwanukuzi Wed., May. 7, 2008 at 10:20 am UTC
It is very interesting to note that the problem of late diagnosis is not limited to resource poor countries but what is particularly challenging to us in Africa is the poor accessibility of care and treatment facilities for rural communities because of poverty and poor travel intfrastructure
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Comment by: A AL YAZOURY Wed., May. 7, 2008 at 10:02 am UTC
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Comment by: Akan Ituk Wed., May. 7, 2008 at 9:33 am UTC
A major problem with the HIV pandemic is that most folks is yet to come in terms with the reality. They "believe" they are uninfectable and as such need not to go for HIV screening. It is not until HIV is succesfully demystified, social immunization will not be achieved.
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Comment by: AMAL Wed., May. 7, 2008 at 7:46 am UTC
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Comment by: Brown Family Foundation Tue., May. 6, 2008 at 9:26 pm UTC
This article was very informative. Our organization promotes HIV Prevention and Detection. We've established a program called "Sisters Can We Talk". This program consist of panel discussions and small group sessions dealing with the subject of HIV and AIDS. We utilize local organizations to provide testing at each event.

This confirms that more opportunities are needed to present testing.
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Comment by: Stuart Lee Carlson Tue., May. 6, 2008 at 5:46 pm UTC
Doc, thanks for your good work!

I've been poz for over 18 years now, and can say with confidence the hiv bug is a manageable disease.

Reason for writing is this: Fat has been stripped from my arms, legs, and butt. If it would help, I am quite able to give you the litany of all the drug regimens between start to the present. In summary first drug was AZT in 1992, when CD4 was 290. Currently I am taking Isentress, Aprivus, Norvir, and Epzicom and my CD4 is 770, wowee ! and VL is und.

For all I know, it seems to be a metabolic puzzle, and fortunately, no facial wasting, thank God.

Please advise.

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