Publications

Antiretroviral (ARV) treatment interruptions are associated with virologic rebound, drug resistance, and increased morbidity and mortality. The Medicare Part D prescription drug benefit, implemented on January 1st, 2006, increased consumer cost-sharing. Consumer cost-sharing is associated with decreased access to medications and adverse clinical outcomes. We assessed the association of Part D implementation with treatment interruptions by studying 125 HIV-infected homeless and marginally housed individuals with drug coverage receiving ARV therapy. Thirty-five percent of respondents reported Medicare coverage and 11% reported ARV interruptions. The odds of ARV interruptions were six times higher among those with Part D coverage and remained significant after adjustment. The majority of Part D-covered respondents reporting ARV interruptions cited increased cost as their primary barrier. Directed interventions to monitor the long-term effects of increased cost burden on interruptions and clinical outcomes and to reduce cost burden are necessary to avoid preventable increases in morbidity and mortality.

Infection with Mycobacterium tuberculosis and Plasmodium species results in upregulation of the host heme oxygenase-1 pathway. In tuberculosis infection, this leads to upregulation of the bacterial "dormancy regulon," whereas in malaria, it enhances the efficiency with which sporozoites develop into exoerythrocytic stages. Here we discuss these findings as well as some of the interesting questions they raise.

The alpha9beta1 integrin accelerates cell migration through binding of spermidine/spermine acetyltransferase (SSAT) to the alpha9 cytoplasmic domain. We now show that SSAT enhances alpha9-mediated migration specifically through catabolism of spermidine and/or spermine. Because spermine and spermidine are effective blockers of K(+) ion efflux through inward-rectifier K(+) (Kir) channels, we examined the involvement of Kir channels in this pathway. The Kir channel inhibitor, barium, or knockdown of a single subunit, Kir4.2, specifically inhibited alpha9-dependent cell migration. alpha9beta1 and Kir4.2 colocalized in focal adhesions at the leading edge of migrating cells and inhibition or knockdown of Kir4.2 caused reduced persistence and an increased number of lamellipodial extensions in cells migrating on an alpha9beta1 ligand. These results identify a pathway through which the alpha9 integrin subunit stimulates cell migration by localized polyamine catabolism and modulation of Kir channel function.