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Could long term bactrim use hinder a rise in CD4 count?

Jul 6, 2010

Hi Dr. Bob,

I think I read recently that the long term use of Bactrim can actually hinder a rise in CD4 counts. Is this true? I have been taking Bactrim for about two years now. My last test results have me at an undetectable VL and CD4 of 249. I have been on Atripla for the same amount of time. Should I ask my HIV doc about stopping the Bactrim since I have been above the 200 threshold for six months now? Is there an additional drug that would help raise the CD4 count? Thanks for your time.


Response from Dr. Frascino


If your CD4 count has been over 200 for the past six months on Atripla, the guidelines suggest you may stop your pneumocystis carinii pneumonia (PCP) prophylaxis. Bactrim is an antibiotic that can be very useful in preventing and, if necessary, treating PCP. Bactrim can have a myelosuppressant effect (decreased production of white blood cells in the bone marrow), however the beneficial effects in prophylaxis/ treatment of PCP far outweigh this effect.

Regarding increasing CD4 counts that fail to respond to effective combination antiretroviral therapy, see below.

Dr. Bob


Since my last consultation 6 months ago my CD4 count has gone up 2 only points from 153 to 155.I got this new result yesturday. My last increase was almost 50 points in 6 months. How concerned should I be about such a slow and disappointing increase? How normal is this slow increase?

I have been on medication for nearly two years...currently Keletra and Truvada. Should I be asking my consultant to be looking at a medication change to affect the CD4 count?

The consultant seems content that my VL is undetectable and I am phsyically very well.

Response from Dr. Frascino


The problem of poor CD4 response despite use of effective antiretroviral therapy that drives the HIV plasma viral load to undetectable levels is a vexing and perplexing problem. We still don't completely understand the reason for this phenomenon (see below). Concern related to inadequate immune reconstitution (rise in CD4 count) on effective antiretroviral therapy is yet another argument in favor of staring treatment early, before CD4 cells decline.

Dr. Bob

why does my CD4 count not improve? (LACK OF CD4 RESPONSE DESPITE TREATMENT, 2010) Apr 23, 2010

Dr. Franscino,

I am a 50 yr old caucasian male. I was diagnosed in June, 2008. At that time my CD4 was around 36 and my VL was well over 350,000. I had symptoms of wasting plus sweats and constant 101+ fevers. It took me two weeks to get in to see an AIDS Dr. here in Mississippi and was started on Atripla, bactrim and zithromycin (the latter has been discontinued). I have been 100% compliant, never missing a single dose. My VL was undetectable after about 9 mos., but my CD4 seems to have peaked at around 260 (highest reading 3 mos ago) and at my last visit was back down to 175 :( . The percentages are consistently 24-27% for the past year or so. Is there anything else I can do to raise the CD4 count? My Dr. says HGH is to risky (side effects) and IL2 is still too experimental, expensive, and not shown to make anyone "healthier" even tho it can at least temporarily boost the memory CD4 count. HELP???!!!

Response from Dr. Frascino


There are a number of potential reasons immune reconstitution (rise in CD4 count) may falter, and they are all complex in nature. These include, among others, ongoing immune inflammation caused by HIV (even when HIV viral load is suppressed to undetectable levels), inadequate functioning of your thymus gland and damage to the architecture of the lymphoid tissues. I would agree with your doctor's advice on IL2 (not helpful) and HGH (many side effects).

There is no doubt that HIVers with suppressed HIV replication, i.e. undetectable viral loads, (even if CD4 response is relative weak) fare better clinically compared to patients not on combination antiretroviral therapy. Consequently treatment is still very much warranted even in those with a poor CD4 response. We are learning more about chronic inflammation and the other potential causes of poor immune reconstitution. Your situation is not uncommon.

This is yet another reasons for early diagnosis and treatment before the CD4 count falls and immune damage occurs.

Stay tuned to this site and we'll keep you posted as this story evolves and more effective treatments come online. One option now would be to try a protease and/or integrase inhibitor-based regimen. This sometimes will give a boost to the CD4 count while continuing to keep the viral load maximally suppressed.

Good luck.

Dr. Bob


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


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


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


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???



Response from Dr. Frascino


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

take on this hard question, please
Has it really been 30 years?

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