HIV nonnucleoside reverse transcriptase inhibitors and trimethoprim- sulfamethoxazole inhibit plasmodium liver stages

Charlotte V. Hobbs, Tatiana Voza, Patricia De La Vega, Jillian Vanvliet, Solomon Conteh, Scott R. Penzak, Michael P. Fay, Nicole Anders, Tiina Ilmet, Yonghua Li, William Borkowsky, Urszula Krzych, Patrick E. Duffy, Photini Sinnis

Research output: Contribution to journalArticle

Abstract

Background.Although nonnucleoside reverse transcriptase inhibitors (NNRTIs) are usually part of first-line treatment regimens for human immunodeficiency virus (HIV), their activity on Plasmodium liver stages remains unexplored. Additionally, trimethoprim-sulfamethoxazole (TMP-SMX), used for opportunistic infection prophylaxis in HIV-exposed infants and HIV-infected patients, reduces clinical episodes of malaria; however, TMP-SMX effect on Plasmodium liver stages requires further study.Methods.We characterized NNRTI and TMP-SMX effects on Plasmodium liver stages in vivo using Plasmodium yoelii. On the basis of these results, we conducted in vitro studies assessing TMP-SMX effects on the rodent parasites P. yoelii and Plasmodium berghei and on the human malaria parasite Plasmodium falciparum.Results.Our data showed NNRTI treatment modestly reduced P. yoelii liver stage parasite burden and minimally extended prepatent period. TMP-SMX administration significantly reduced liver stage parasite burden, preventing development of patent parasitemia in vivo. TMP-SMX inhibited development of rodent and P. falciparum liver stage parasites in vitro.Conclusions.NNRTIs modestly affect liver stage Plasmodium parasites, whereas TMP-SMX prevents patent parasitemia. Because drugs that inhibit liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. Understanding HIV drug effects on Plasmodium liver stages will aid in optimizing treatment regimens for HIV-exposed and HIV-infected infected patients in malaria-endemic areas.

Original languageEnglish (US)
Pages (from-to)1706-1714
Number of pages9
JournalJournal of Infectious Diseases
Volume206
Issue number11
DOIs
StatePublished - Dec 1 2012

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HIV Reverse Transcriptase
Reverse Transcriptase Inhibitors
Plasmodium
Sulfamethoxazole Drug Combination Trimethoprim
Parasites
Liver
Plasmodium yoelii
HIV
Parasitemia
Malaria
Rodentia
Plasmodium berghei
Falciparum Malaria
Opportunistic Infections
Plasmodium falciparum
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

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HIV nonnucleoside reverse transcriptase inhibitors and trimethoprim- sulfamethoxazole inhibit plasmodium liver stages. / Hobbs, Charlotte V.; Voza, Tatiana; De La Vega, Patricia; Vanvliet, Jillian; Conteh, Solomon; Penzak, Scott R.; Fay, Michael P.; Anders, Nicole; Ilmet, Tiina; Li, Yonghua; Borkowsky, William; Krzych, Urszula; Duffy, Patrick E.; Sinnis, Photini.

In: Journal of Infectious Diseases, Vol. 206, No. 11, 01.12.2012, p. 1706-1714.

Research output: Contribution to journalArticle

Hobbs, CV, Voza, T, De La Vega, P, Vanvliet, J, Conteh, S, Penzak, SR, Fay, MP, Anders, N, Ilmet, T, Li, Y, Borkowsky, W, Krzych, U, Duffy, PE & Sinnis, P 2012, 'HIV nonnucleoside reverse transcriptase inhibitors and trimethoprim- sulfamethoxazole inhibit plasmodium liver stages', Journal of Infectious Diseases, vol. 206, no. 11, pp. 1706-1714. https://doi.org/10.1093/infdis/jis602
Hobbs, Charlotte V. ; Voza, Tatiana ; De La Vega, Patricia ; Vanvliet, Jillian ; Conteh, Solomon ; Penzak, Scott R. ; Fay, Michael P. ; Anders, Nicole ; Ilmet, Tiina ; Li, Yonghua ; Borkowsky, William ; Krzych, Urszula ; Duffy, Patrick E. ; Sinnis, Photini. / HIV nonnucleoside reverse transcriptase inhibitors and trimethoprim- sulfamethoxazole inhibit plasmodium liver stages. In: Journal of Infectious Diseases. 2012 ; Vol. 206, No. 11. pp. 1706-1714.
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AU - Hobbs, Charlotte V.

AU - Voza, Tatiana

AU - De La Vega, Patricia

AU - Vanvliet, Jillian

AU - Conteh, Solomon

AU - Penzak, Scott R.

AU - Fay, Michael P.

AU - Anders, Nicole

AU - Ilmet, Tiina

AU - Li, Yonghua

AU - Borkowsky, William

AU - Krzych, Urszula

AU - Duffy, Patrick E.

AU - Sinnis, Photini

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N2 - Background.Although nonnucleoside reverse transcriptase inhibitors (NNRTIs) are usually part of first-line treatment regimens for human immunodeficiency virus (HIV), their activity on Plasmodium liver stages remains unexplored. Additionally, trimethoprim-sulfamethoxazole (TMP-SMX), used for opportunistic infection prophylaxis in HIV-exposed infants and HIV-infected patients, reduces clinical episodes of malaria; however, TMP-SMX effect on Plasmodium liver stages requires further study.Methods.We characterized NNRTI and TMP-SMX effects on Plasmodium liver stages in vivo using Plasmodium yoelii. On the basis of these results, we conducted in vitro studies assessing TMP-SMX effects on the rodent parasites P. yoelii and Plasmodium berghei and on the human malaria parasite Plasmodium falciparum.Results.Our data showed NNRTI treatment modestly reduced P. yoelii liver stage parasite burden and minimally extended prepatent period. TMP-SMX administration significantly reduced liver stage parasite burden, preventing development of patent parasitemia in vivo. TMP-SMX inhibited development of rodent and P. falciparum liver stage parasites in vitro.Conclusions.NNRTIs modestly affect liver stage Plasmodium parasites, whereas TMP-SMX prevents patent parasitemia. Because drugs that inhibit liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. Understanding HIV drug effects on Plasmodium liver stages will aid in optimizing treatment regimens for HIV-exposed and HIV-infected infected patients in malaria-endemic areas.

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