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Thursday, November 21, 2013

HIV associated TMA: Is this an ADAMTS13 mediated entity or CMV related?

HIV associated TMA was more common in the AIDS era. After advent of HAART therapy, this entity is rare.

Traditional Risk factors are:
Low CD4 count, high viral load, concurrent Hep C and AIDS, blacks

Most secondary causes of TMA, treating the underlying cause or removing the underlying medication would treat the TMA(HUS or TTP variant).
Interestingly, one study looked at TMA from HIV in more detail and the use of plasma exchange. They prospectively looked at biological differences and response to the therapy. Response was much better in the HAART + plasma exchange arm versus HAART arm alone.  Interestingly, 80% of the patients that developed TMA , had either low ADAMTS13 levels or antibodies to them-in which case TPE or plasma exchange would offer benefit. Does HIV modulate ADAMTS13 or lead to inhibition?

Another study looked at the role of CMV viremia for causing TMA in HIV patients. They looked at clinical and pathological data for 29 patients with TMA and HIV infection. The diagnosis of TMA was confirmed by histological examination of kidney biopsy specimens (18 cases). Endothelial cytomegalovirus (CMV) inclusions were associated with TMA in nine of 18 cases, whereas histological examination did not detect CMV in any control specimens (P < .001).  This study using a case controlled method demonstrated a link of TMA and clinical systemic CMV infection by an odds ratio of close to 4.

So lets revise the risk factors for HIV associated TMA

1. Low CD4, high viral load
2. AIDS
3. Blacks
4. Hep C
5. Concurrent CMV viremia
6. ADAMTS13 inhibition or deficiency.



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