Izidakamizwa Ezinamandla Ezikhethwe Ngokwelapha Okokuqala
I-Integrase inhibitors (eyaziwa nangokuthi integrase strand transfer inhibitors, noma i-INSTIs) iyisigaba esinamandla semithi elwa negciwane lesandulela ngculaza esivimbela igciwane lesandulela ngculazi ekuhlanganiseni i-genetic coding (genome) ibe yi-DNA yesitokisi samagciwane. Lokhu kwenza ngokuvimbela i-enzyme ebizwa ngokuthi i-integrase futhi, ngokwenza kanjalo, yenza kube nzima ukuthi i-HIV iphinde iphendule.
I-Isentress (ratelgravir) yayiyi-INSTI yokuqala evunyiwe yi-US Food and Drug Administration (FDA) ngo-Okthoba 12, 2007.
Konke okukhulunywe ngakho, kukhona okwamanje amakhemikhali omuthi we-INSTI avumelekile kanye nemithi emine ehleliwe ehlangene nezidakamizwa lapho i-INSTI iyisici
- Isentress (ratelgravir)
- I-Tivicay (i-dolutegravir)
- I-Vitekta (elvitegravir)
- I-Triumeq (dolutegravir + abacavir + lamivudine)
- I-Stribild (elvitegravir + cobicistat + tenofovir + emtricitabine)
- I-Genvoya (elvitegravir + cobicistat + tenofovir AF + emtricitabine)
Ngenkathi isidakamizwa se-integrase, i-Dutrebis (ratelgravir + lamivudine), nayo ivunyiwe yi-US Food and Drug Administration, ayitholakali ngokwezomnotho e-US okwamanje.
Abakhiqizi bezidakamizwa i-ViiV ne-Janssen Pharmaceuticals okwamanje babambisana nomunye umuthi wokuhlanganisa ozohlanganisa i-dolutegravir ne- Edurant (i-rilpilvirine) yezidakamizwa . Omunye ukhetho othembisayo we-INSTI, i-cabotegravir, uqaliswa ukuhlolwa kwabantu kwesigaba se-Phase III.
Njengesigaba semithi, i-integrase inhibitors ibhekwa njengenzuzo ekwelapheni ukutheleleka nge-HIV, ngezidingo ezilula zokufaka izidakamizwa, imiphumela emibi engezansi, amaphrofayli wokumelana okuthuthukisiwe nokuqina okukhulu.
Ngenxa yalokho, ama-INSTIs ahlukaniswa njengendlela yokukhetha ukwelashwa okhethwayo emihlahlandlela eminingi ye-HIV, kuhlanganise nalabo base-US
Isiqondiso samanje esivela eMnyangweni wezeMpilo wezeMelika nase-Human Services sinikeza integrase inhibitors njengendlela ekhethwayo, i-ejenti yokuqala yabantu ababesanda kuphathwa nge-HIV. Eqinisweni, kulezi zinketho eziyisithupha zokwelashwa okwamanje zinconywa iziguli ezishaye ukwelashwa, ezinhlanu ziqukethe i-integrase inhibitor njenge-agent ye-backbone yezidakamizwa.
Ungayichaza kanjani umsebenzi we-Inhibitors?
I-HIV ihlanganisa i-genome yayo yesandulela ngculazi ku-DNA yesitokisini esitokisini ngezinqubo ezinhlanu:
- I-enzyme ye-integrase ibophezela ku-HIV DNA, okwakhiwa kuyo inqubo ebizwa ngokuthi i- reverse transcription .
- I-HIV DNA isilungele ukuhlanganiswa ngenqubo ebizwa ngokuthi i- cleaving, okuyinto eyenza ngokoqobo imfucuza yegciwane lesandulela ngculazi , ebeka izikhala ezivulekile ngesakhiwo sayo.
- I-strand ehlanganisiwe yabe isetjenziswa ku-nucleus yesitoreji esitokisini nge- pore yenyukliya .
- Uma usungene ngaphakathi kwe-nucleus, i-HIV DNA idluliselwa ku-DNA ye-host in okubizwa ngokuthi yi- strand transfer reaction. Kulesi sigaba, i-DNA yegciwane ihlasela i-DNA yeselula, ihlukanise izibopho ezibamba i-DNA ndawonye futhi zizihlanganisa ngokwazo ngokusebenzisa izikhala zamakhemikhali kwi-DNA strand.
- Lokhu kuhlasela kuvuselela impendulo yokuzivikela yemvelo ebizwa ngokuthi ukukhishwa kwe-gap , lapho i cell cell lizovuselela ngokuzenzakalelayo noma yikuphi ukulimala ku-DNA, ngokuyisisekelo eholele ekutheni kuthathwe inhlawulo ye-genetic coding.
Ngokumvimbela i-enzyme ye-integrase, yonke inqubo yokuhlanganiswa imisiwe, iphela ngokuphumelelayo umjikelezo wegciwane. Kodwa-ke, njengoba ukuhlanganiswa kungenye yezinyathelo ezimbalwa zemjikelezo ye-HIV, ezinye izidakamizwa zithathwa ukuze zivimbele ezinye izigaba, zivimbele phambili i-HIV ekuphindiseni nasekuqinisekiseni ukuthi umsebenzi wegciwane lesandulela ngculaza ususwe ngokuphelele (njengoba kulinganiswa nomthamo wegciwane lesandulela ngculaza).
Imiphumela emibi kanye nokucabangela
Ngokungafani nezinye izigaba zemithi ye-HIV, i-integrase inhibitors isebenza ngqo ezindleleni zegciwane ngokwazo kunamaseli. Njengalokhu, bathambekele kakhulu emiphumeleni emibi, ngokuyinhloko isifo sohudo, isisindo sokukhipha isisu, ukukhathala, ukuphathwa ikhanda nokulala.
Iningi lala miphumela emibi, noma kunjalo, ihlala isikhathi eside futhi ngokuvamile ixazulula eyedwa. Uma kuthiwa, uma uhlangabezana nesenzakalo esibi ngenkathi uthatha inhlanganisela yemithi ye-integrase inhibitor, cebisa udokotela wakho noma umtholampilo ngokushesha. Ungayeki ukwelashwa ngaphandle okungenani ukhulume nochwepheshe oqeqeshiwe. Ukuyeka nokushintsha ngaphambi kwesikhathi kungenza umonakalo omkhulu kunokuhle.
Ngokufanayo, kuyilapho i-integrase inhibitors engaphansi kwesimo sokuphikisa izidakamizwa ngaphambi kwesikhathi , kufanele ugweme ukulinganiselwa okungekho noma izikhala ekwelapheni. Ukuphika kwenzeka lapho amazinga ezidakamizwa egazini eqala ukuwa, okuvumela amagciwane omzimba ukuba avele futhi aqhubeke. Uma lokhu kwenzeka, izidakamizwa zakho ngeke zikwazi ukusebenza kanye naphambi futhi kungenzeka, kwezinye izimo, zihluleke.
Njengoba i-integrase inhibitors ihlala egazini legazi isikhathi eside, iyakwazi ukuvimbela ukuguqulwa kwe-HIV ngisho nalapho ukuphuzwa kwegazi kungabanjwanga ngaso sonke isikhathi. Kodwa kubalulekile ukuqonda ukuthi ukuphazamiseka okwesikhashana akuqondiswanga nokuthi ukunamathela kwansuku zonke kuyisihluthulelo empumelelweni yokwelapha.
Imithombo:
I-US Food and Drug Administration (FDA). "Iphakethe Lokuvunyelwa Kwezidakamizwa - Igama LamaDakamizwa: Isentress (ratelgravir) Amathebulethi angu-400mg." I-Silver Spring, e-Maryland; Okthoba 12, 2007.
I-National Institute of Allergy and Infectious Diseases (NIAID) "Ukuthuthukiswa Kwezidakamizwa zeHIV / AIDS." I-Bethesda, e-Maryland; ibuyekezwe ngoJulayi 21, 2015.
UMnyango wezeMpilo kanye nezinsizakalo zabasebenzi (DHHS). "Imihlahlandlela yokusetshenziswa kwama-Antiretroviral Agents ku-HIV-1-Adult Adult and Adolescents." I-Rockville, e-Maryland; ibuyekezwe ngoJanuwari 28, 2017; kufinyelelwe kuMashi 24, 2017.
UCraigie, R. noBushman, F. "Ukuhlanganiswa kwe-HIV DNA." I-Cold Spring Harbour Perspectives in Medicine. Julayi 2012; 2 (7): a006890.
Bushman, F .; Fujiwara, D .; noCraigie, R. "Ukuhlanganiswa kwe-DNA ye-Retroviral eqondiswa iprotheyini yokuhlanganiswa kwe-HIV in vitro." Isayensi. Ngo-September 28, 1990; 249 (4976): 1555-1558.