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

U Lek-uthai, Rossarin Suwanarusk, R Ruengweerayut, T Skinner-adams, F NOSTEN, D Gardiner, P Boonma, Kim Piera, Kathy Andrews, Barbara MacHunter, J MCCARTHY, Nicholas Anstey, Ric Price, B Russell

    Research output: Contribution to journalArticle

    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. Copyright � 2008, American Society for Microbiology. All Rights Reserved.
    Original languageEnglish
    Pages (from-to)2435-2441
    Number of pages7
    JournalAntimicrobial Agents and Chemotherapy
    Volume52
    Issue number7
    Publication statusPublished - 2008

    Fingerprint Dive into the research topics of 'Stronger activity of human immunodeficiency virus type 1 protease inhibitors against clinical isolates of Plasmodium vivax than against those of P. falciparum'. Together they form a unique fingerprint.

  • Cite this

    Lek-uthai, U., Suwanarusk, R., Ruengweerayut, R., Skinner-adams, T., NOSTEN, F., Gardiner, D., Boonma, P., Piera, K., Andrews, K., MacHunter, B., MCCARTHY, J., Anstey, N., Price, R., & 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.