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CD4 descrescendo Par II
Mar 27, 2010

My t-cells are on a decrescendo! Part 1 (Submitted Mar 22, 2010)

Dear Dr. Bob,

I am feeling very, very low and was hoping you might be able to help me find some perspective in my situation. I was diagnosed in May of 2006, with a t-cell count of 109, and VL of 5,000. I started treatment immediately (Sustiva/Truvada) and within a month or two my VL was undetectable and my cd4 count started to rise. By April of 2008, my t-cell count was 324, although at that time (for the first time since treatment) I had a blip with my VL, which rose to 184. I switched to Atripla at that time, and my doctor took me off of the PCP prophylaxis. After that time, I went back to (and have remained) VL "undetectable, although it seems my CD 4 count has hit the brick wall it has not risen further, and in fact has fallen. It is now back down to 247. Below is a bit of the snap shot of my trajectory:

AT DIAGNOSIS 5/5/06 VL: 5,000 CD4: 109

11/04/07

VL: Undetectable CD4: 220

4/17/08

VL: 184 CD4: 324 CD4%: 12.8% Total T Cells: 1,745 T-Suppressor: 1420

7/02/09

VL: Undetectable CD4: 266 CD4%: 15.6% Total T Cells: 1,114 T-Suppressor: 831

3/05/10

VL: Undetectable CD4: 247 CD4%: 14.6% Total T Cells: 1,100 T-Suppressor: 847

My doctor says I am doing ok, but I am worried I am not. I asked him if I should be back on the PCP prophylaxis, and he says no. But I am worried shouldnt I be taking it again if I am under 300?

And in general, I am very concerned that my t-cells have leveled off, or are actually falling. I have been completely compliant with my regimen, although my career as a classical solo musician requires that I travel internationally several times a month, so I am always jumping time zones and the international dateline to Australia, to Europe, to Asia, and am wondering if that has something to do with my lackluster response to my treatment.

I am currently still on Atripla, and am wondering what I should do? I was quite optimistic when I started treatment, but now I am very scared that I am on a downward spiral. Please forgive me for bothering you with this I know I am off topic for your blog but you give the best answers and advice of anybody on The Body, so I am turning to you. Should I be looking for a new doctor? New medication? Or stay the course? I leave for another international tour in a month or so, and am frightened that I will make myself even worse. I am only in my mid-40s, and never considered retiring from performing. But maybe all this traveling is compromising my treatment. Cant imagine giving up the piano and letting this virus win, however. Thank you for any insight you can give me.

Dear Dr. Bob, I don't know if this is important info, but I made an error in the info I sent you earlier this evening. My CD4 count peaked at 324 on 4/17/2009, NOT 2008 (which corresponded with my "viral blip") and then I was back down to CD4 266, but undetectable, just 3 months later, on 7/02/09. So the numbers should have been:

AT DIAGNOSIS 5/5/06 VL: 5,000 CD4: 109

11/04/07

VL: Undetectable CD4: 220

4/17/09

VL: 184 CD4: 324 CD4%: 12.8% Total T Cells: 1,745 T-Suppressor: 1420

7/02/09

VL: Undetectable CD4: 266 CD4%: 15.6% Total T Cells: 1,114 T-Suppressor: 831

3/05/10

VL: Undetectable CD4: 247 CD4%: 14.6% Total T Cells: 1,100 T-Suppressor: 847

Response from Dr. Frascino

Hello Concert Pianist,

I, too, am a classically trained concert pianist, although I stopped concertizing when I decided to go to medical school. I have returned to the stage in recent years, primarily to help raise funds for my charitable AIDS foundation (The Robert James Frascino AIDS Foundation [www.concertedeffort.org]). I often wonder what my life would have been like had I taken the other fork in the road and continued to perform. I still do a fair amount of traveling. Consequently I totally understand the challenges of taking antiretrovirals on time while trying to cope with multiple time zones, international datelines and the stress related to modern day travel in a post-9/11 world.

Regarding your "decrescendo," I understand why it makes you "agitato." In general, you have had an excellent virologic response to combination antiretroviral therapy with your HIV plasma viral load staying essentially undetectable, despite one small inconsequential blip. Immunologically, however, your response has been far less robust. You have increased significantly from a CD4 count of 109 at the time of diagnosis in May 2006 to a count in the 220-300 range. There are a number of potential reasons for a less than anticipated CD4 response. See below. It may be worth trying a protease inhibitor- and/or integrase inhibitor-based regimen, assuming your resistance profile does not preclude the use of these agents. I have seen some HIVers kickstart their CD4 count this way. It's certainly not a sure thing, but it may well be worth a try and would be my next step. Switching from one completely suppressive regimen to another is considered safe.

As for PCP prophylaxis, the formal cutoff is a CD4 of 200. You're certainly getting close, as there is some day-to-day variability in CD4 counts.

Regarding your concert schedule, if possible, build in some downtime. Arrive early and stay longer with each engagement. I know you've probably already booked for this season, but as you make future engagements, just give yourself an extra day on either side. Not only will it give your body a chance to acclimate a bit, but you'll also have more time to try out the piano, rehearse in the venue and relax and also perhaps see the sites of your concert destination the day after your performance.

Let me know if you're performing in or around San Francisco. Who knows, perhaps we could even share the stage for a benefit concert here in the Bay Area.

I absolutely agree with your comment on not giving up the piano or letting the virus win! I applaud that decision with a resounding BRAVO!

Good luck. I'm here if you need me, OK? Now it's back to some Scriabin Etudes for me. Tricky devils, but I do enjoy them.

Dr. Bob

stubborn T-Cells (CD4 COUNTS NOT INCREASING DESPITE UNDETECTABLE VIRAL LOAD, 2010) Jan 16, 2010

I have been + for 10 years. My initial VL was 300,000 and T's was 79. My initial therapy was Epivir, Zerit and Viramune along with Bactrim. I have since changed therapy due to the Zerit and now on Truvada and Viramune. My VL went undectable within the first 3 months and besides the occasional blip, has stayed there. But, my T's stubbornly stay within the 200 range. My doctor, an infectious disease specialist, is not worried about this at all. He says there is no rhyme or reason to why my T's do not increase beyond 300. He says that I have very healthy T's even though I don't have many. And that there is no way (besides maybe interluken, which he is strongly against) to raise them medically. And changing my current therapy would not be smart since I am undetectable. I have never had an OI, just get the occasional cold and allergies. I am more worried about my long term health with low T's. I found out I was + just by a random test. Is there something my doctor may be missing? Any tests to see what else could be keeping my T-4's low? He did test me about a year ago for Pylori and that came back negative. Are there any drugs or alternative therapies available to increase T-4's? Thank you

Response from Dr. Frascino

Hi,

I've addressed this problem a number of ties previously in this forum (see below for an example) and have very little new to add at this time. This problem of inadequate immune reconstitution (rise in CD4 cells) is another reason why we encourage combination antiretroviral medication be started before there is significant loss of CD4 cells. This also argues for early HIV testing to determine who is infected and close clinical monitoring of those known to have acquired the virus.

Dr. Bob

Low Cd 4 count (CD4 COUNTS NOT INCREASING DESPITE UNDETECTABLE VIRAL LOAD, 2009) Jul 18, 2009

6/28/07 I tested hiv positive. At the time viral load was 145000 and cd4 was 50. I was put on atripla and one month later I was undectable and cd4 was 255. Its been two years now of being undectable and the cd4 is not going up. The range over the last 2 years for my cd4 has been 198 to 260, my last cd 4 was 223. Why is it not going up? I have been depressed and started Zolot 100mg. Could depression keep the cd4 count down? Does the Sustiva in atripla cause depression? Would a protease inhibitor help?

Response from Dr. Frascino

Hello,

Dr. Henry already addressed your question regarding lack of immune reconstitution despite driving HIV plasma viral load to undetectable levels for a considerable period of time. I'll reprint his response below. I completely agree with his comments. I'll also post below some recent information about lymph node fibrosis, which, I believe, may well be the main culprit responsible for your CD4 counts not increasing.

Depression would not be the cause of your CD4 counts not having risen as expected. Sustiva can exacerbate some types of depression. I tend not to recommend Sustiva in folks who are experiencing significant depression. Would a protease inhibitor help? Possibly. It may be worth a try for two reasons. First it will allow you to discontinue Sustiva (in light of your depression) and second it may result in improved immune reconstitution.

Good luck!

Dr. Bob

Cd 4 Count not going up Jul 7, 2009

6/28/07 I tested Hiv Positive and one week later my doctors found my cd 4 count to be 50 and my viral load to be 145,000. I was told i probably had the virus for about 6 to 8 years without knowning. They immediately put me on Atripla and Bactrim DS and one month later I was undectable and cd 4 was 255. Six months later I was taken off Bactrim. Its been two years of being undectable now, and my cd4 count is not going up. The cd 4 count range over the last two years has been 203 to 260, my last cd4 was 223 and still undectable. Why is my cd4 count not improving?

Response from Dr. Henry

There are many reasons why the CD4 count may not recovery well despite good HIV suppresssion. Possibilities include poor thymus function, genetic factors (HLA and CCR5 and other markers), destroyed lymphoid tissues architecture, ongoing immune activation, and others. Patients seem to do better with suppressed virus levels even when the CD4 recovery is poor compared to patients not taking ART so treatment still has a positive clinical effect. Your situation is not that uncommon and is a strong argument for identifying HIV infection early and starting treatment at higher CD4 counts. KH

Falling CD4 despite undetectable viral load?????? Jun 25, 2009

Dr. Bob,

My HIV doc is totally stumped!!!! I'm on HAART and my viral load has been undectctable for over a year and yet my CD4's are continuing to decline. Is there any scientific rational for why this is happening???

Thanks,

Coltman

Response from Dr. Frascino

Hi,

Yes, but it is preliminary information and rather complex. Simply put the latest research indicates the cause may involve fibrosis in the lymph nodes. This research is preliminary but HIVers whose normal lymph node architecture has been replaced with collagen appear to be most at risk. I'll reprint some information about this topic below.

Dr. Bob

The Puzzle of CD4-Cell Depletion Despite Good Viral Suppression In some patients, CD4-cell counts fail to rise as expected. Could extensive lymph node fibrosis be responsible?

We expect that when combination antiretroviral therapy (ART) suppresses a patient's HIV viremia, a steady increase in CD4-cell count will ensue. In some patients, however, such increases are minimal or fail to occur, and in others, CD4-cell counts plummet after an initial rise, even though viral load remains undetectable. The combination of ddI and tenofovir has been associated with these aberrant CD4-cell responses, but the underlying mechanism is unclear, and the phenomenon is also seen in patients taking other drugs.

In a recent study, NIH researchers sought evidence to support any of several hypothetical explanations for the aberrant CD4-cell responses seen in four patients on combination ART whose CD4 counts had fallen from a median of 719 cells/mm3 to a median of 227 cells/mm3 despite persistently undetectable plasma viral loads. Three of the four patients were receiving a regimen containing tenofovir and ddI.

Residual replicating HIV did not seem to be the problem: Results of ultrasensitive PCR and assays for peripheral blood mononuclear cellassociated HIV RNA and proviral HIV DNA and of assays for cell-associated HIV RNA and proviral DNA in mononuclear cells from inguinal lymph nodes were similar to those obtained in other, successfully treated patients. Thymic production of naive CD4 cells was similar to that seen in successfully treated age-matched controls. No evidence of occult drug resistance sabotaging treatment was found. Changing ART regimens to avoid the tenofovir/ddI combination had little effect on CD4-cell counts during the follow-up period (median duration, 10 months).

The single unusual finding was a striking abnormality in inguinal lymph node architecture in the four patients: From 24% to 34% of the T-cell zone was replaced by collagen. In contrast, collagen levels in six successfully treated patients have been reported to range from 2% to 12% (J Clin Invest 2002; 110:1133).

Comment: We do not know the exact pathogenesis of CD4-cell depletion in untreated HIV infection, so creating logical hypotheses to explain aberrant CD4 responses is especially challenging. These authors offer the intriguing suggestion that the unusual lymph node architecture documented in all four patients in this study may be related to (or even responsible for) the inadequate CD4-cell response i.e., that CD4-cell depletion is independent of specific components of an antiretroviral regimen and is instead caused by lymph node fibrosis. They note that such architectural damage may well be "clinically irreversible with currently available interventions."

Abigail Zuger, MD

Published in AIDS Clinical Care June 1, 2009



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