Merck's 2DR Kev Kho Mob Ua Ntej Ntawm Kab Mob HIV Theem 2b Muaj Qhov Cuam Tshuam Sib Piv rau Cov Tshuaj Phom

Lub Kaum Hlis 8, Merck tshaj tawm qhov kev ntsuam xyuas ntawm lub qhov ncauj tshiab nucleoside rov qab transcriptase translocation inhibitor (NRTTI) islatravir thiab Pifeltro (doravirine) ob-tshuaj yeeb tshuaj (2DR) ntawm 2020 International sablaj ntawm HIV Tshuaj Kho (HIV Glasgow 2020) 96-lub lis piam cov ntaub ntawv los ntawm Theem 2b mus sib hais (NCT03272347) rau kev kho mob-tsis paub zoo (piv txwv li, tsis yog kho yav tas los) HIV-1 cov laus muaj tus kab mob.

Cov txiaj ntsig tau pom tias qhov 2DR no zoo ib yam li cov tshuaj triad Delstrigo (doravirine / 3TC / TDF) hauv kev tswj hwm qhov feem ntawm cov neeg mob uas muaj kev tiv thaiv kab mob (HIV-1 RNA< 50="" daim="" ntawv="" ml),="" thiab="" tau="" zoo="" ib="" yam="" li="" 48-="" lub="" lim="" tiam="" dhau="" los.="" cov="" ntaub="" ntawv="" ntxiv="" 96-lub="" limtiam="" qhia="" tau="" tias="" hauv="" 2dr="" kho="" pawg="" thiab="" delstrigo="" kho="" pawg,="" qhov="" sib="" piv="" ntawm="" cov="" neeg="" mob="" uas="" tau="" ua="" raws="" li="" cov="" ntsiab="" lus="" ntawm="" cov="" neeg="" mob="" tsis="" ua="" haujlwm="" (pdvf)="" muaj="" tsawg="" heev,="" thiab="" tsis="" muaj="" ob="" pawg="" kho="" mob="" ua="" tau="" raws="" li="" cov="" qauv="" rau="" kev="" siv="" tshuaj="" kuaj="" ua="">

Ntxiv rau, Merck kuj tau tshaj tawm cov txiaj ntsig ntawm ntu 1 / 1b kawm ntawm MK-8507, ib lub lim tiam ntawm lub qhov ncauj tsis-nucleoside rov qab transcriptase inhibitor (NNRTI) hauv kev nthuav dav. Cov ntaub ntawv qhia tau hais tias kev siv tshuaj tiv thaiv kab mob thiab tshuaj noj ntawm MK-8507 txhawb kev tshuaj xyuas ntxiv ntawm kev siv tshuaj ib zaug ib lub lim tiam los kho txoj kev kho mob raws li ib feem ntawm kev siv tshuaj tiv thaiv kabmob (ARV) rau kev kho mob rau HIV-1 Kev kho mob ntawm kev kis mob.

Pifeltro (doravirine, 100mg) yog hom tshiab ntawm ib zaug ib hnub NNRTI, uas tsim nyog rau kev sib xyaw nrog lwm cov tshuaj ARV rau kev kho mob HIV-1 cov neeg laus muaj tus kabmob HIV-1, tshwj xeeb: (1) Rau cov neeg mob uas tsis muaj yav dhau los ARV kev kho mob yav dhau los; (2) Rau cov neeg mob uas tau txais kev pabcuam ruaj khov ntawm ARV kom ua tiav kev tiv thaiv kabmob (HIV-1 RNA< 50="" daim="" ntawv="" ml),="" tsis="" muaj="" keeb="" kwm="" ntawm="" kev="" kho="" mob="" tsis="" ua="" haujlwm,="" thiab="" tsis="" muaj="" kev="" paub="" hloov="" chaw="" uas="" cuam="" tshuam="" nrog="" doravirine="" tsis="" kam="" hloov,="" hloov="" lawv="" tam="" sim="" no="" arv="">

Delstrigo yog qhov sib xyaw ua ke peb-hauv-ib qho tshuaj suav nrog txhaj tshuaj tsis tu ncua ntawm NNRTI doravirine tshiab (DOR, 100mg), lamivudine (3TC, 300mg) thiab tenofovir disoproxil fumarate (TDF, 300mg). Cov tshuaj yog ib cov ntsiav tshuaj ib hnub ib zaug, siv los ua kev npaj ua tiav rau kev kho mob rau cov neeg laus muaj tus kabmob HIV-1, tshwj xeeb: (1) rau cov neeg mob uas tsis muaj keeb kwm tshuaj mob ARV; (2) rau cov neeg mob uas tau txais kev ruaj khov ARV raws tu qauv kom ua tiav kev tiv thaiv kev tua kab mob (HIV-1 RNA< 50="" daim="" ntawv="" ml),="" tsis="" muaj="" keeb="" kwm="" ntawm="" kev="" kho="" tsis="" ua="" tiav,="" thiab="" tsis="" muaj="" kev="" paub="" hloov="" chaw="" uas="" cuam="" tshuam="" nrog="" kev="" tawm="" tsam="" ntawm="" txhua="" feem="" ntawm="" delstrigo="" (doravirine,="" 3tc,="" tdf),="" hloov="" nws="" cov="" haujlwm="" arv="" tam="" sim="" no.="" delstrigo="" daim="" ntawv="" qhia="" tshuaj="" muaj="" lub="" thawv="" ntawv="" ceeb="" toom="" dub="" uas="" qhia="" txog="" qhov="" kev="" pheej="" hmoo="" ntawm="" kev="" kis="" tus="" kab="" mob="" siab="" b="" (hbv)="" tom="" qab="" kho="">

Cov ntaub ntawv ua tau zoo thiab kev nyab xeeb

Hauv kev sim thoob ntiaj teb no, ntau lub chaw tshuaj ntsuam xyuas, cov neeg laus raug mob HIV-1 tau raug xaiv los ntawm kev sib kis (1: 1: 1: 1: 1) rau 4 ib zaug-txhua hnub hauv kev kho mob qhov ncauj: islatravir 0.25 mg (n=29), 0.75 mg (n=30), 2.25 mg (n=31) ua ke nrog doravirine (100 mg) thiab 3TC (300 mg), Delstrigo (n=31). Tom qab tsawg kawg 24 lub lim tiam ntawm kev kho mob, cov neeg mob hauv 3 pawg islatravir kho mob uas ua tiav cov tshuaj tua kab mob (HIV-1 RNA< 50="" daim="" ntawv="" ml)="" thiab="" tsis="" tau="" raws="" li="" pdvf="" cov="" qauv="" tau="" hloov="" mus="" rau="" 2dr="" kho="" (suav="" nrog="" tib="" lub="" tshuaj="" ntawm="" islatravir="" thiab="" doravirine="" [100mg]],="" tsis="" suav="">

Hauv lub lis piam 96, islatravir + doravirine regimen tswj kev tiv thaiv kev tua kabmob (HIV-1 RNA< 50="" daim="" ntawv="" ml)="" ntawm="" txhua="" qib.="" tshwj="" xeeb,="" ntawm="" 96="" lub="" lis="" piam="" ntawm="" kev="" kho="" mob,="" 86="" .2%="" (25/29),="" 90.0%="" (27/30),="" 67.7%="" (21/31)="" ntawm="" cov="" neeg="" mob="" nyob="" hauv="" islatravir="" 0.25mg,="" 0.75mg,="" thiab="" 2.25mg="" pawg="" pab="" pawg="" sib="" xyaw,="" txhawm="" kom="" tswj="" kev="" tiv="" thaiv="" mob="" vaum,="" tus="" nqi="" yog="" 80.6%="" (25/31)="" hauv="" pawg="" delstrigo="" kho="" mob.="" hauv="" cov="" islatravir="" 2.25mg="" koob="" tshuaj="" pawg,="" cov="" lej="" txo="" qis="" tus="" neeg="" mob="" vijtsam="" mob="" feem="" ntau="" yog="" vim="" tus="" lej="" siab="" thim="" rov="" qab="" rau="" lub="" sijhawm="" kho="" 48="" lub="" lis="" piam="" ua="" ntej="" kev="" tshawb="">

Hauv lub lis piam 96, piv nrog Delstrigo pab pawg kho mob (22.6%), qhov sib piv ntawm cov neeg mob (7.8%) nrog kev cuam tshuam txog tshuaj (AE) hauv txhua pawg pawg ntawm islatravir tau qis dua (7.8%). Txij lub lim tiam 48 txog rau lub lim tiam 96, tsis muaj lwm qhov kev phiv loj heev uas cuam tshuam nrog tshuaj nyob hauv ib pawg twg. Raws li cov txiaj ntsig no, qhov 0.75mg koob tshuaj islatravir yuav siv rau kev tsim kho ntxiv.

PDVF kev soj ntsuam tau

Daim ntawv tshuaj ntsuam 96-lub limtiam pom tau tias qhov tshwm sim ntawm PDVF muaj tsawg heev, thiab HIV-1 RNA qib ntawm txhua tus neeg mob tsis kho vim PDVF yog< 80="" daim="" ntawv="" ml,="" uas="" yog="" qis="" dua="" thaj="" chaw="" hauv="" chaw="" kuaj="" mob="" ntawm="" 200="" cov="" ntawv="" luam="" ml.="" tsis="" muaj="" ib="" tus="" neeg="" mob="" tau="" ntsib="" cov="" qauv="" tshuaj="" tiv="" thaiv="" kab="" mob="" (hiv-1="" rna=""> 400 daim ntawv / ml). PDVF tau txhais raws li: kis rov kis kab mob nrog paub tseeb tias HIV-1 RNA qib ≥50 daim ntawv / ml tom qab tiv thaiv kev tiv thaiv mob, lossis tsis teb rau kev kho thiab lees paub tias HIV-1 RNA copies50 daim ntawv / ml.

Lub lim tiam 96, tag nrho ntawm 7 tus neeg mob tau ntsib cov ntsiab lus ntawm PDVF thiab kev sim siab tau raug txiav. Raws li tau hais ua ntej, 48 lub lis piam, 6 tus neeg mob tau lees paub PDVF, thiab qhov xwm txheej ntawm islatravir txhua qhov kev sib xyaw kho mob yog 5.6% (5/90; 4 tus neeg mob rov qab, 1 qhov xwm txheej tsis teb), thiab Delstrigo pawg yog 3.2% ( 1/31; 1 rov qab). Hauv pawg 2.25 mg islatravir koob tshuaj pab pawg, tsuas yog 1 tus neeg mob tsis kho vim PDVF (rov ua dua). Cov neeg mob hauv ib pawg kho mob tsis tau ua tiav cov qauv tshuaj tiv thaiv kev tiv thaiv, vim tias txhua tus neeg mob uas tau ua tiav cov lus txhais ntawm PDVF tau muaj qib HIV-1 RNA< 80="" daim="" ntawv="" ml.="" lub="" sijhawm="" 42-hnub="" soj="" qab,="" 3="" ntawm="" 7="" tus="" neeg="" mob="" uas="" tau="" tsum="" tsis="" ua="" haujlwm="" vim="" pdvf="" tseem="" pom="" tias="" muaj="" viremia="" qes="" qis="" tom="" qab="" hloov="" mus="" rau="" kev="" muab="" tshuaj="">

Cov lus qhia soj ntsuam raum kev nyab xeeb

Lub sijhawm tshawb xyuas 96-lub limtiam qhia tau tias tsis muaj teeb meem kev mob raum. Ntsuas cov tshuaj creatineine raug ntsuas ntawm txhua qhov kev tuaj xyuas (nrog rau hnub 1, lub lim tiam 48, thiab lub lim tiam 96). Kev kwv yees tus nqi glomerular filtration (eGFR) tau suav nrog siv cov khoom noj hloov kho rau cov kab mob hauv raum (MDRD).

Thaum 48th thiab 96th lub lis piam, kev hloov pauv nruab nrab ntawm cov ntshav dej creatinine thiab eGFR ntawm txhua pawg kho mob tau muaj tsawg. Ob tus neeg mob hauv pawg 0.25 mg islatravir muaj qhov kev ua kom zoo tshaj in0.5 mg / dL los ntawm theem pib, uas tau daws teeb meem hauv kev tshuaj xyuas tom ntej: 1 tus neeg mob nyob hauv 16 lub lis piam (1.7 mg / dL), thiab lwm tus neeg mob Thaum 60 lub lim tiam (1.7 mg / dL) thiab 84 lub lim tiam (1.9 mg / dL). Tsis muaj ib tus neeg mob' s teev ntshav cov tshuaj creatinine nce ≥1.0 mg / dL lossis ob npaug. 12% (11/90) hauv pawg islatravir kho pab pawg thiab 16% (5/31) nyob hauv pawg Delstrigo muaj qhov kev txo qis hauv eGFR ntau dua 30% piv rau cov hauv paus, thiab feem ntau nws tau hloov chaw.

4% (4/90) ntawm cov neeg mob hauv Islatravir pawg kho mob tau eGFR< 60ml="" min="" 1.73m2,="" ntawm="" cov="" 3="" cov="" neeg="" mob="" hloov="" chaw="">< 60ml="" min="" 1.73m2="" hauv="" plaub="" kis="" tau="" los="" ntawm="" lub="" hauv="" paus="" rau="" 96th="" lub="" lim="" tiam).="" cov="" lim="" roj="" biomarkers,="" suav="" nrog="" cov="" tso="" zis="" tso="" zis="" albumin,="" albumin="" creatinine="" piv,="" β-2="" microglobulin="" creatinine="" piv,="" lossis="" retinol="" khi="" cov="" protein="" creatinine="" piv,="" tsis="" muaj="" kev="" hloov="" pauv="" tseem="" ceeb="" hauv="" tsev="" kho="" mob.="" cov="" koob="" tshuaj-teb="" kev="" sib="" raug="" zoo="" ntawm="" islatravir="" ua="" ke="" nrog="" doravirine="" rau="" ntawm="" lub="" raum="" tsis="" tau="" pom,="" thiab="" tsis="" muaj="" tus="" neeg="" mob="" tso="" tseg="" kev="" kho="" mob="" vim="" tias="" qhov="" tshwm="" sim="" tsis="" zoo="" lub="">