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AIDS and HIV Therapy: Cyclin-Dependent Kinase Inhibitors May Be Effective Against HIV Nephropathy






 

-- Researchers in the United States say that cyclin-dependent kinase inhibitors may be an effective treatment for patients with HIV related kidney dysfunction

"The glomerular lesions of HIV-associated nephropathy (HIVAN) are associated with the expression of HIV-1 in podocytes," explained Dr. Peter J. Nelson and colleagues at Mount Sinai School of Medicine in New York City.

Cyclin-dependent kinase inhibitors reduced HIV expression by podocytes in vitro, Nelson and coauthors found.

The researchers added flavopiridol or roscovitine, which block the activity of cyclin-dependent kinase-9, to cultures of podocytes. Both drugs blocked HIV transcription in these cells, they said.

Roscovitine was more effective at preventing podocyte proliferation than flavopiridol, study data showed. However, flavopiridol had a lower inhibitory concentration than its counterpart, with an IC50 of 25 nM compared with the 3 µM IC50 roscovitine.

Both agents enabled the expression of podocyte differentiation markers, which had been suppressed by HIV gene expression (Suppression of HIV-1 expression by inhibitors of cyclin-dependent kinases promotes differentiation of infected podocytes, J Am Soc Nephrol 2001 Dec;12(12):2827-31.

"These results suggest that inhibition of HIV-1 transcription decreases podocyte proliferation and permits the reexpression of differentiation markers," Nelson and coworkers concluded. "Thus, suppression of HIV-1 transcription by selective cyclin-dependent kinase-9 inhibitors may be a useful therapeutic strategy for the treatment of HIVAN."

The corresponding author for this report is Dr. Peter Nelson, Division of Nephrology, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1243, New York, NY 10029, USA. E-mail: peter.nelson@mssm.edu.

Key points reported in this study include

  • Cyclin-dependent kinase inhibitors reduce HIV expression by infected podocytes

  • Suppression of HIV expression enabled the reexpression of podocyte differentiation markers

  • These agents may be an effective treatment for HIV associated nephropathy

This article was prepared by AIDS Weekly editors from staff and other reports.



 


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Information in this article was accurate in January 28, 2002. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.