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, R., Ruengweerayut, R., Skinner-Adams, T. S., Nosten, F., Gardiner, D. L., Boonma, P., Piera, K.A., Andrews, K. T., MacHunter, B., McCarthy, J. S., Anstey, N. M., Price, R. N. and Russell, B. (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. doi:10.1128/AAC.00169-08

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Author Lek-Uthai, U.
Suwanarusk, R.
Ruengweerayut, R.
Skinner-Adams, T. S.
Nosten, F.
Gardiner, D. L.
Boonma, P.
Piera, K.A.
Andrews, K. T.
MacHunter, B.
McCarthy, J. S.
Anstey, N. M.
Price, R. N.
Russell, B.
Title Stronger activity of human immunodeficiency virus type 1 protease inhibitors against clinical isolates of Plasmodium vivax than against those of P. falciparum
Formatted title
Stronger activity of human immunodeficiency virus type 1 protease inhibitors against clinical isolates of Plasmodium vivax than against those of P. falciparum
Journal name Antimicrobial agents and Chemotherapy   Check publisher's open access policy
ISSN 0066-4804
Publication date 2008-07-01
Year available 2008
Sub-type Article (original research)
DOI 10.1128/AAC.00169-08
Open Access Status File (Publisher version)
Volume 52
Issue 7
Start page 2435
End page 2441
Total pages 8
Editor G. M. Eliopoulos
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Subject C1
9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
110804 Medical Virology
Formatted 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 mdr1 copy number was present in 33% (3/9) of isolates and that of P. vivax mdr1 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.
Q-Index Code C1
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