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Stronger activity of human immunodeficiency virus type 1 protease inhibitors against clinical isolates of Plasmodium vivax than against those of P. falciparum

Lek-Uthai, U., Suwanarusk, Rossarin, Ruengweerayut, R., Skinner-Adams, T., Nosten, F., Gardiner, D. L., Boonma, Prapaporn, Piera, Kim A., Andrews, K. T., Machunter, Barbara, McCarthy, J. S., Anstey, Nicholas M., Price, Ric N. and Russell, Bruce (2008). Stronger activity of human immunodeficiency virus type 1 protease inhibitors against clinical isolates of Plasmodium vivax than against those of P. falciparum. Antimicrobial Agents and Chemotherapy,52(7):2435-2441.

Document type: Journal Article

IRMA ID 10026xPUB7
Title Stronger activity of human immunodeficiency virus type 1 protease inhibitors against clinical isolates of Plasmodium vivax than against those of P. falciparum
Author Lek-Uthai, U.
Suwanarusk, Rossarin
Ruengweerayut, R.
Skinner-Adams, T.
Nosten, F.
Gardiner, D. L.
Boonma, Prapaporn
Piera, Kim A.
Andrews, K. T.
Machunter, Barbara
McCarthy, J. S.
Anstey, Nicholas M.
Price, Ric N.
Russell, Bruce
Journal Name Antimicrobial Agents and Chemotherapy
Publication Date 2008
Volume Number 52
Issue Number 7
ISSN 1098-6596   (check CDU catalogue open catalogue search in new window)
Start Page 2435
End Page 2441
Total Pages 7
Place of Publication Washington, United States
Publisher American Society for Microbiology
Field of Research 0605 - Microbiology
1108 - Medical Microbiology
HERDC Category C1 - Journal Article (DEST)
Abstract Recent studies using laboratory clones have demonstrated that several antiretroviral protease inhibitors (PIs) inhibit the growth of Plasmodium falciparum at concentrations that may be of clinical significance, especially during human immunodeficiency virus type 1 (HIV-1) and malaria coinfection. Using clinical isolates, we now demonstrate the in vitro effectiveness of two HIV-1 aspartic PIs, saquinavir (SQV) and ritonavir (RTV), against P. vivax (n = 30) and P. falciparum (n = 20) from populations subjected to high levels of mefloquine and artesunate pressure on the Thailand-Myanmar border. The median 50% inhibitory concentration values of P. vivax to RTV and SQV were 2,233 nM (range, 732 to 7,738 nM) and 4,230 nM (range, 1,326 to 8,452 nM), respectively, both within the therapeutic concentration range commonly found for patients treated with these PIs. RTV was fourfold more effective at inhibiting P. vivax than it was at inhibiting P. falciparum, compared to a twofold difference in SQV sensitivity. An increased P. falciparum mdrl copy number was present in 33% (3/9) of isolates and that of P. vivax mdrl was present in 9% of isolates (2/22), but neither was associated with PI sensitivity. The inter-Plasmodium sp. variations in PI sensitivity indicate key differences between P. vivax and P. falciparum. PI-containing antiretroviral regimens may demonstrate prophylactic activity against both vivax and falciparum malaria in HIV-infected patients who reside in areas where multidrug-resistant P. vivax or P. falciparum is found.
DOI http://dx.doi.org/10.1128/AAC.00169-08   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
 
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