160418 Role of Retinoids in the Pathogenesis and Treatment of HIV infection: Hypothesis

Monday, November 5, 2007

Anthony R. Mawson, MA, DrPH , Department of Preventive Medicine, University of Mississippi Medical Center, Jackson, MS
Sridevi Alla, MBBS , STD/HIV Bureau, Mississippi State Department of Health, Jackson, MS
The pathogenesis of HIV and the cause of the decline in CD4 T cells remain obscure. Several contradictory observations suggest a potential role for retinoids. For instance, some studies suggest that vitamin A supplementation is associated with disease improvement, others with disease worsening. HAART (highly active antiretroviral therapy) decreases viral load and increases the number of CD4 T cells. However, this revolutionary treatment is associated with the development of drug resistance and toxic side-effects resembling retinoid toxicity; protease inhibitors also increase retinoic acid (RA) signaling. We propose that HIV interacts with retinoids in that the virus requires retinol for replication and in turn generates RA, which destroys CD4 T cells via apoptosis. We also propose that HAART limits HIV replication via a retinoic acid-induced temporary feedback inhibition of retinoid metabolism in the liver, which lowers the availability of serum retinol. We suggest that the increased exogenous RA induced by HAART promotes retinol esterification and impairs hepatic mobilization, leading to cholestasis. Over time, resistance to HAART due to reduced feedback inhibition of RA on retinoid metabolism enhances the availability of retinol and promotes renewed viral replication, along with the production of RA and destruction of CD4 T cells. The cholestasis-induced reflux of stored biliary retinoid metabolites also contributes to the adverse metabolic and cardiovascular side-effects of HAART. If these speculations are correct, HIV viral replication could be more effectively prevented by retinoic acid receptor (RAR) antagonism than by drugs that increase retinoid signalling.

Learning Objectives:
1.To discuss the pathogenesis of HIV. 2.To describe about the role of retinoids (vitamin A and its congeners) in the pathogenesis of HIV. 3.To introduce a new theory linking retinoids with HIV pathogenesis.

Presenting author's disclosure statement:

Any relevant financial relationships? No
Any institutionally-contracted trials related to this submission?

I agree to comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines, and to disclose to the participants any off-label or experimental uses of a commercial product or service discussed in my presentation.