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Resistance (I know, not your "department.") ( BLIPS, 2009)
Apr 25, 2009

Dear Dr. Frascino, I know that drug resistance is not your official "department" here at The Body, but the Drug Resistance Expert here no longer takes questions, and I am very anxious about my situation. I tried asking my question to the "Understanding Your Labs" Forum, but they did not respond. You are so knowledgeable about all areas of HIV and AIDS, I am wondering if you could help me understand what is going on in my case.

To put it as briefly as possible, I was diagnosed in July, 2006 with a tcell count of 90, and a viral load of 5,000. I was immediately put on Truvada/Sustiva, plus a prophylaxis agains PCP. Within a month or so, my viral load was undetectable, and my tcells started (slowly) rising: By July 2007, tcells had risen to 190, by July 2008, to 225. I just had my labs done this week (April 2009, obviously), and my tcells are up to 325.

My viral load has been undetectable for this entire period. Until this week's labs. Now, however, the viral load has risen to <184.

I have been completely adherent to my regime since I started taking meds. I have never missed a dose EVER. My only deviation is that I fly internationally for work frequently, to far flung places like Sydney, Singapore, and various places in Europe (from where I live in San Fran.) My doctor told me to always take my meds at bedtime, in whatever time zone I am in. This means, on travel days in some directions, that there is sometimes a 5 to 12 hour delay in the time I would have usually taken the meds. But I followed his instructions.

I should add that one year ago I was switched from Sustiva/Truvada to Atripla.

I am terrified that this rise in my CD4 tcells is signaling the start of drug resistance, and I am so upset as I have tolerated the meds with no side effects whatsoever. I should add I have also never had an opportunistic infection.

I am part of a program, and so see a different doctor on various visits. My current doctor is not one for explaining things very well, and when I asked about the viral load rise to 184, he just shrugged his shoulders, and said "We'll see what it is in 6 months." And left the room. He did not add "Don't worry, it's nothing."

So I am very confused, and very upset. Don't have a clue as to whether this is a blip (and if so, why now?) or if I am starting drug resistance. (And if so, did I cause it by my travel schedule?) Any information you can impart would be appreciated so very much. And if I am indeed developing a drug resistance, what would this mean to my overall prognosis? Would the alternative therapies be less effective? Are they likely to cause more side effect? I wish I understood what is happening here.

If this is happening, could it have been the switch from Sustiva/Truvada to Atripla which caused the rise in viral load? Could it be the deviation in medication timing caused by my international travel?

Thank you so much again for your help. Again, I fully realize that this is not under the "brief" of your particular site, but I would be so appreciative for your help.

It would be lovely if my own doctor would answer some of these questions, but they just seem to shrug. Straight men, what are you going to do with them.

Thanks so much -- Geo

P.S. I'm so sorry, but two other questions: Why am I still taking the antibiotic to prevent PCP? I thought that should have stopeed at tcell 200, but I'm still on it. Also, my tcell rise over 2 and 3/4 years seems slower than a lot of people seem to experience. Is going from 90 to 325 in 2 years and 8 months a reasonable outcome, or is this slow?

Response from Dr. Frascino

Hi Geo,

Glad to help.

First, I should mention I'm certainly not impressed with a healthcare program that makes you see a different doctor on each visit. Nor am I impressed with Dr. Shrugged-shoulders! What's up with that? That you are receiving such suboptimal care in a city like San Francisco is all the more shocking! Generally speaking we have excellent HIV care in San Francisco.

Let me try to address your many concerns (which should have already been thoroughly addressed by any competent HIV specialist!)

1. A rise in HIV plasma viral load to 184 copies after more than 2.5 years of being consistently undetectable on combination antiretroviral therapy is not at all uncommon. Most likely this is indeed a transient rise in viral replication, a "blip," which will subside spontaneously. Blips can be caused by a number of underlying conditions ranging from an intercurrent infection to a recent vaccination. See below.

2. Is this the start of drug resistance? Most likely no, it is not for several reasons. First, your viral load is extremely low (184 copies). Second, you've been "completely adherent . . . never missed a dose . . ." and you've had an undetectable viral load for over two years.

3. Could it be caused by your travel schedule? No, this is not likely. An occasional delay of 5 to 12 hours due to your travel schedule should not affect this regimen. Sustiva in particular has a very long half life.

4. Would drug resistance, if you did develop it, affect your overall progress? No, as long as you could be switched to another completely suppressive regimen. (You still have many options, as Atripla (Sustiva/Truvada) is your first regimen.

5. Would alternative therapies be less effective? No.

6. Would alternative therapies cause more side effects? Every drug has its own unique side effect and toxicity profile. If someone developed resistance to one regimen and needed to switch, this would not change the side effect profile of the drugs in the new regimen.

7. Is your blip the result of changing from Sustiva/Truvada to Atripla? No. These are identical combinations. Atripla merely combines the three drugs into one tablet.

8. Why are you still taking the antibiotics for PCP prophylaxis? Good question! Probably because you are seeing so many different doctors and no one is paying close enough attention to what's going on with you! The updated guidelines clearly indicate primary prophylaxis for PCP should be discontinued in adults who have responded to combination antiretroviral therapy with an increase in CD4 count to greater than 200 for longer than three months. Clearly you have met these guidelines criteria for quite some time. You might want to point that out to whomever you see at your next visit. Better yet, why not find a health plan that allows you to consistently see the same HIV physician?!

9. Is your rise in CD4 count slower than anticipated? This is a difficult question to answer, because there is great variability from person to person for a whole variety of reasons involving both the virus (viral strain, viral fitness, etc.) and the host (genetics, immune integrity, concurrent infections, medication adherence, etc.). It is true some folks respond more dramatically and quickly than others. Your rise from 90 to 325 (essentially tripling) is significant and encouraging. How high will your counts go and over what period of time no one knows. We are learning it's far better never to let the CD4 cells drop to low levels, because we can't always bring them back. Even when we do manage to increase their numbers, we still aren't certain these new cells function as effectively as the ones HIV initially wiped out. This realization is one of the factors that are driving us to begin treatment earlier and earlier.

Good luck. I'm here if you need me (even if it's not my "official department," OK?).

Finally, as for "straight men, what are you going to do with them?" Well, I suppose we could give them a queer-eye makeover for a start, eh?

Dr. Bob

blips Sep 6, 2008

Are frequent blips in VL (under 2000) common? I've had about 4 now after 6 years of being undectable. Wondering why this occurs as I am very adherent to taking my meds. Thanks fo your help.

Response from Dr. Frascino

Hello,

It's a bit difficult to give specific advice on "blips," because different folks define them differently. For instance, if your blips approach 2,000, that's fairly high. Most are in the hundreds. In general, a blip is a very transient rise in HIV plasma viral load from undetectable to low-detectable levels, which returns to undetectable levels quickly (within weeks). There are different theories as to the cause of blips, including:

1. release of virus from reservoirs or protected sanctuaries in the body where replication of drug-sensitive virus continues at a low level;

2. drug-resistant virus;

3. Immunological events, such as a concurrent infection or vaccination, which suddenly increase the number of infection-susceptible immune cells and result in a viral feeding frenzy. This subsequently causes a transient blip; and

4. variations in drug levels in a person hovering on the margins of total viral suppression.

Whatever the cause, most studies have suggested that there is no association between blips and loss of virologic control or disease progression. That said, if indeed you are blipping over 1,000 copies/ml, I'd suggest you get a resistance test (genotype/phenotype) at the time of your next blip, as you've now had four blips following a six-year period of being undetectable. The resistance test will let you know if you've developed any resistance to your current drug regimen.

Good luck.

Dr. Bob

Blips (part 2) Sep 10, 2008

Dr Bob, I think i may have worded my last question wrong. You answered it last week. I have had 4 blips during the 6 years I've been undectable. These did not occur concurrently and a few have only been in the hundreds. My doctor does not seem concerned but again, I was curious as to why I've had so many. Also does the VL have to be at a certain level for an accurate geno test? Thanks in advance.

Response from Dr. Frascino

Hello,

May have worded your last question wrong???? There is no "may" about it! (See below!)

I concur with your HIV specialist. Four "blips" over six years is not all that uncommon and not worrisome. You can read more about "blips" in the archives.

As for genotype and phenotype resistance assays, generally the HIV plasma viral load must be above 500 copies.

Be well.

Dr. Bob



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