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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.
Afiliación
  • Hobbs CV; NIH/NIAID/Laboratory of Malaria Immunology and Vaccinology, Rockville, Maryland 20852, USA.
J Infect Dis ; 206(11): 1706-14, 2012 Dec 01.
Article en En | MEDLINE | ID: mdl-23125449
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium / Combinación Trimetoprim y Sulfametoxazol / Inhibidores de la Transcriptasa Inversa / Hígado / Malaria Límite: Animals / Female / Humans Idioma: En Revista: J Infect Dis Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium / Combinación Trimetoprim y Sulfametoxazol / Inhibidores de la Transcriptasa Inversa / Hígado / Malaria Límite: Animals / Female / Humans Idioma: En Revista: J Infect Dis Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos