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The Puzzle of CD4-Cell Depletion Despite Good Viral Suppression

• The Puzzle of CD4-Cell Depletion Despite Good Viral Suppression
• Abberent CD4 responses
• Lower CD4 Counts
• CD4 depletion in the face of good viral load suppression
• CD4-Cell Depletion Despite Good Viral Suppression - Let's look at the thymus

The Puzzle of CD4-Cell Depletion Despite Good Viral Suppression

MURUGAN SANKARANANTHAN, Tirunelveli, Tamilnadu- INDIA, 2 Jun 2009 1:55 AM EST

Competing interests: None declared

Few other possibilities may be thought off in these lines: People who had been infected with both HIV 1&2 (we had similar patients ,atleast 13 nos.), will be responding to treatment as far as their HIV1 is concerned and their Viral load will be nondetecble level, whereas their HIV2 may not be effectively suppressed with the treatment containinig a regimen of NNRTI. The viral load test also will not reveal the HIV 2 load. Infection with HIV 2 will persist in these individuals. So their CD4 response will also not to be at the expected level.

The other things are extreme protein malnutrition with HIV infection or Lymph nodal diseases associated with HIV infection also may contibute.

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Abberent CD4 responses

OLAYINKA . A. OLASODE, OBAFEMI AWOLOWO UNIVERSITY, NIGERIA, 2 Jun 2009 7:20 AM EST

Competing interests: None declared

This might actually support early commencement of HAART at higher CD4 levels before active lymph nodes are replaced by collagen.In the developing world where Viral Loads are rarely done and treatment with HAART is commenced at CD4 of 200cells/ul this issue is vital food for thought.

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Lower CD4 Counts

DD C, 3 Jun 2009 8:38 PM EST

Competing interests: None declared

I've been on HAART since I was infected (acute phase) almost six years ago. At first, my CD4 count was in the 1,000 range, after starting meds. Now it is in the 700 range. My viral load has always been negative. I am in Truvada and Issentres. My doctors tell me that my CD4/CD8 count is very good, and since my VL is negative I need not be concerned. But I do not agree.

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CD4 depletion in the face of good viral load suppression

Balarabe Sani-Garko, ABU Teaching Hospital, Zaria, 5 Jun 2009 10:09 AM EST

Competing interests: None declared

HIV/AIDS management also includes proper and appropriate management of opportunistic infections, these infections if untreated/undertreated may alter outcomes in HIV management. Malnutrition again may be contributary. In response to a comment saying HAART is started at CD4 levels of 200 in developing countries, I am not sure that is a fact. I am not aware of any developing country that practices that. In Nigeria where I practice, the National guideline states that HAART starts at CD4 of 350 or less. I am also aware of at least seven(7) centres where viral load is part of routine HIV management with support from the Harvard school of public health, this includes ABUTH where I practice.

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CD4-Cell Depletion Despite Good Viral Suppression - Let's look at the thymus

AP Oppenheimer, 12 Jun 2009 12:27 PM EST

Competing interests: None declared

I think that this issue could be more of a central cause than a peripheral one or better yet a combination of the two. Reviewing the origin/life of the CD4 lymphocytes, first from the bone marrow (progenitor stem cells) to the thymus, where they are successively educated from DN cells to DP cells and finally to CD4+ CD8- cells which are then released to lymphnodes and lymph and blood circulation , migth lead to some answers. The first cells to show their CD4 markers are the DP (double positive) cells in the thymus. HIV will primarily infect CD4 cells, so we can assume that even the thymus cells could be infected and we know that HIV is thymotoxic and causes decreased lymphopoiesis in the thymus, especially the strains that are CXCR4 trophic. The more severe the infection the less is the possibility of thymus recovery. At this point sensitive ART will destroy infected cells but the thymus may be beyond recovery and the production of new batches of CD4 cells will not happen, reflecting a "poor peripheral CD4 count". Lymphnodes showing extensive fibrosis will decrease further this count as the few CD4 cells that manage to leave the thymus are going to get entangled in the lymphnodes and die before entering the blood circulation. To test this theory one needs to look at the CXCR4 receptor status of the patients with poor responses and biopsy their thymus to identify/quantify the different cell lines. Of course increasing the number of studied subjects is crucial too, as is defining the severity of the infection.

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