title: HIV treatments have malaria gametocyte killing and transmission blocking activity.
abstract: BACKGROUND
  Millions of individuals being treated for human immunodeficiency virus (HIV) live in malaria-endemic areas, but the effects of these treatments on malaria transmission are unknown. While drugs like HIV protease inhibitors (PIs) and trimethoprim-sulfamethoxazole (TMP-SMX) have known activity against parasites during liver or asexual blood stages, their effects on transmission stages require further study.
  
  
  METHODS
  The HIV PIs lopinavir and saquinavir, the nonnucleoside reverse-transcriptase inhibitor nevirapine, and the antibiotic TMP-SMX were assessed for activity against Plasmodium falciparum transmission stages. The alamarBlue assay was used to determine the effects of drugs on gametocyte viability, and exflagellation was assessed to determine the effects of drugs on gametocyte maturation. The effects of drug on transmission were assessed by calculating the mosquito oocyst count as a marker for infectivity, using standard membrane feeding assays.
  
  
  RESULTS
  Lopinavir and saquinavir have gametocytocidal and transmission blocking activities at or approaching clinically relevant treatment levels, while nevirapine does not. TMP-SMX is not gametocytocidal, but at prophylactic levels it blocks transmission.
  
  
  CONCLUSIONS
  Specific HIV treatments have gametocyte killing and transmission-blocking effects. Clinical studies are warranted to evaluate these findings and their potential impact on eradication efforts.
authors.affiliation: Laboratory of Malaria Vaccinology and Immunology, NIH/NIAID, 12735 Twinbrook Pkwy, Rockville, MD 20852, USA. charlotte.hobbs@nih.gov
authors.forename: Charlotte V
authors.initials: CV
authors.lastname: Hobbs
authors.forename: Takeshi Q
authors.initials: TQ
authors.lastname: Tanaka
authors.forename: Olga
authors.initials: O
authors.lastname: Muratova
authors.forename: Jillian
authors.initials: J
authors.lastname: Van Vliet
authors.forename: William
authors.initials: W
authors.lastname: Borkowsky
authors.forename: Kim C
authors.initials: KC
authors.lastname: Williamson
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Duffy
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D061466:Lopinavir / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000517:prevention & control / Q000635:transmission; D019829:Nevirapine / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D019258:Saquinavir / Q000494:pharmacology*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D000962:Antimalarials; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D019829:Nevirapine; D019258:Saquinavir
keywords: HIV; TMP-SMX; antiretrovirals; gametocytes; malaria; transmission
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