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CD4 cell production

Aug 17, 2005

"Someone diagnosed with primary HIV infection at or shortly after seroconversion may have an opportunity to intervene with immediate therapy. If they choose to do so, this intervention may prevent the widespread early immune damage related to HIV and possibly lower the set point of HIV and favorably alter long-term outcomes even when medications are stopped. This is by no means proven, but some pilot studies have shown promising and intriguing results. One of the crucial determinants may be starting HAART within weeks of seroconversion." Dr Pierone, Jul 26, 2005

Can you provide a little bit more information about 'early immune damage'. I understand CD4 cells are manufactured in bone marrow. HIV doesn't attack bone marrow directly so how does HIV affect CD4 cell production. I emphasise 'production'. Why might CD4 cell production not return to normal levels (understanding that normal levels vary from person to person) if the viral load can be reduced significantly regardless how recent the HIV infection occurred?

Response from Dr. Pierone

Hello and thanks for posting.

The bone marrow contains both mature and immature white blood cell, red blood cells, and platelets. HIV infects WBCs (lymphocytes and monocytes/macrophages) and this infection certainly includes those cells that reside in the bone marrow.

But the bone marrow appears not to be the primary site of immune attack by HIV. Recent studies have shown that within the first 2 weeks after acquisition of HIV infection more than half of the total body nave memory CD4 cells are destroyed. This process occurs primarily in gut associated lymph tissue (the gut actually is the location of much of our "immune system"). The hope would be that prompt initiation of HAART within 2 weeks of infection - which is before or during seroconversion would prevent this loss of nave memory CD4 cells.

After primary infection with HIV there is chronic immune activation which leads to a heightened state of CD4 cell activation and proliferation (and CD4 death I might add, since activated CD4 cells soon die). After initiation of HAART, the immune activation quiets down and the remaining nave lymphocyte population leads to reconstitution of the immune system. We do know that HAART works even many years after primary infection and can lead in many cases to normal or near normal blood CD4 cell counts.

But the hope (currently unproven) is that rapid treatment of primary infection would lead to an improved long-term outcome absent the need for HAART. I hope this explanation clarifies why there is interest in rapid treatment of primary HIV infection.

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