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Nonhuman Primate Models for HIV Cure Research 英文参考文献
Viewpoints
NonhumanPrimateModelsforHIVCureResearch
CristianApetrei1,2*,IvonaPandrea1,3,JohnW.Mellors4
1CenterforVaccineResearch,UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,2DepartmentofMicrobiologyandMolecularGenetics,School
of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 3Department of Pathology, School of Medicine, University of Pittsburgh,
Pittsburgh,Pennsylvania,UnitedStatesofAmerica,4DepartmentofMedicine,SchoolofMedicine,UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesof
America
Shytaj et al. [1] report that complete
suppressionofSIVmacreplicationcanbe
achievedinrhesusmacaquesbyacombi-
nation of five antiretroviral (ARV) drugs,
whichtheauthorsterm‘‘mega-HAART’’.
This combination consists of the three-
drug nucleoside reverse transcriptase in-
hibitor (tenofovir/emtricitabine) and inte-
grase inhibitor (raltegravir) regimen often
usedintreatmentstudiesofsimianimmu-
nodeficiency virus (SIV)-infected rhesus
macaques, intensified with the protease
inhibitor darunavir (pharmacokinetically
enhanced by ritonavir) and the CCR5
antagonistmaraviroc.Achievingcomplete
suppression of SIVmac in rhesus ma-
caquesisanimportantstepindeveloping
ananimalmodelforHIV-1cureresearch
because it parallels the effects of antiret-
roviral therapy in HIV-infected humans.
Without complete suppression, testing of
becausethepandemicHIV-1subtypesdo
not replicate in monkey species [18],
simiancounterpartsderivedfromnatural-
ly infected sooty mangabeys, such as
SIVmac/smm, must be used [19]. Al-
thoughSIVsmmisnotcompletelydistinct
fromitsHIVrelatives,beingthecauseof
the HIV-2 epidemic [20], the differences
inARVsusceptibilityandpharmacokinet-
ics have restricted the use of the RM/
SIVmacmodelsforantiretroviraltherapy.
Nevertheless,manyARVsareactivein
vitroandinvivoagainstSIVmac[14,21],
andstudiesofantiretroviraltherapy(ART)
inmacaqueshavebeenreported[21–24].
In most of these studies, however, com-
plete control
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