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Follow-up to Confused About When To Start Meds?
Oct 8, 2009

Dr. McGowan,

I want to thank you for you quick response. Also, don't apologize for being "long-winded." I'm trying to get as much info as I can, so please talk as much as you want.

My previous question was about starting HAART right away, even with very good numbers, and whether that would cause resistance sooner.

I have a couple questions: I've read and been told once I start meds I must take them everyday or I may develop resistance. Why do I hear so many people on the web say they have/are taking a drug holiday? I read where one guy said he took an 18-month holiday per his doc. Wouldn't that cause resistance?

2nd: I've read studies where HIVers should live an almost normal life-span. Then I read on amfar.com in their "Basic Facts About HIV/AIDS" section that "most people cannot tolerate long-term HAART treatment" and "roughly half will experience treatment failure within 2 years due to resistance." Why the difference in optimism? I realize AMFAR needs to point out that meds aren't good enough and we need funding to find a cure.

3rd: I keep hearing today's meds are very tolerable and don't have the bad side-effects from years past. Then, I read where HIVers are getting sick from kidney and heart problems.

Most of the info I read is very optimistic. However, I do find some very scary info as well. I guess I need to just be thankful there are meds and this isn't the death sentence it use to be.

Thanks so much!

Response from Dr. McGowan

Thanks for the follow-up. These are very important issues. Some of the confusion comes from the fact that things are changing rapidly in the way we treat HIV. Older information is mixed with newer info which can be confusing.

1st: Regarding drug resistance and "drug holidays". HIV develops drug resistance if the virus is allowed to grow in the presence of the drug. If the level of drug in the blood is too low to kill it then the virus will be able to copy itself while the drug is around. Whenever the virus copies itself it makes mistakes in its genetic code called mutations. These mutations can allow the new "baby" viruses to grow differently than the parent. Some of these mutations might allow a virus to survive better in the face of exposure to a medication. If the medication is around than that mutant virus would have an advantage above the rest and will grow more strongly than the others (because the others would be killed by the medication). In this way drug resistant virus gets "selected" out from the swarm of virus in the body. As long as the medication is around at a low level then this virus will survive and make copies and add more mutations that will make it even stronger.

This is what happens if you have too little medicine in your system. The way that happens is if doses are missed and the blood level of meds is allowed to drop below the amount needed to kill the virus 24 hours a day.

The way to avoid this is by taking all the doses of the meds every day. In that way the blood level is always enough to completely shut off the virus. If the virus can't copy itself it can't make mutations and it can't get resistant. That is the reason that we tell people that once they start the meds they must be adherent and take all the doses to prevent resistance. There is no reason to believe that as long as the virus is undtectable that drug resistance will occur. This is what the clinical trials have shown...the people who take their meds and remain undetectable have long-term success.

On the other hand...if you are on no meds. Or stop all your meds at the same time (as opposed to missing doses here and there). Then there is NO medicine in the blood. If there is no medicine in the blood than there is no advantage for the virus to accumulate drug resistance mutations because it will offer no benefit for its survival. However, if you are off meds you also can't benefit from having suppressed virus.

2) There is a difference between how people respond to medication in research studies and in "real life". Research studies pick the patients who are most likely to take their meds, are very motivated and not using drugs, etc. In real life we have to treat everyone as they come. So while responses to treatment in trials can be as high as 90% or better, in real life it is lower. The reason for these poorer responses is generally due to poor adherence to treatment for many reasons such as forgetfullness, drug interactions, side effects, drug use, depression, mental illness, etc. If a person remians committed to treatment and is motivated they will remain suppressed once they get there and resistance is rare.

3)We are learning that HIV can cause damage to many organs in the body. This is due to a combination of the effects of low CD4 cell counts (and the loss of balance of the immune system that protects our organs against infections and tumors, etc) and chronic inflammation that is induced by the virus. In addition, some of the medications may cause increases in the lipids (fats and cholesterol) in the blood or add to kidney disease that is present beforehand. These increased lipids may accelerate the risk for heart attack and stroke, which may be even more likely if the process was started off by HIV causing damage to the blood vessels through inflammation. The risks have to be kept into context. Certainly at lower CD4 counts the risk of HIV outweighs the slight potential increased risk from heart disease that may be caused by the meds. That descision is easy. But at higher CD4 counts the balance may be less clear. If a person has multiple risk factors for heart disease or kidney disease than that added risk may be important. However not treating also carries a risk becasue HIV contributes to these diseases as well. This debate is one of the hottest now and the balance must be individualized to deceide when is the best time to intervene for any person.

I think it is great that we are at a point when we can have the luxury of weighing several options for treatment and the time to plan the best approach to treatment. This is a long way from where we were a few years ago when we would do anything we could to just slow the process down.

Joe



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