Izidakamizwa ezinamandla ezikhethwa ngonyango lokuqala
I-Integrase inhibitors (eyaziwa nangokuthi integrase strand transfer inhibitors, okanye i-INSTIs) yinkampani enamandla yeyeza- antiretroviral ekhusela i-HIV ukuba idibanise i-genetic coding (genome) kwi-DNA yesitokethi segciwane. Iyenjenjalo ngokuvimbela i-enzyme ebizwa ngokuba yi-integrase kwaye, ngokwenza njalo, yenza ukuba kube nzima ukuba i-HIV iphendule.
Isentress (ratelgravir) yi-INSTI yokuqala eyavunyelwa yi-US Food and Drug Administration (FDA) ngo-Oktobha 12, 2007.
Yonke into echazwe, kukho iimolomleli zezidakamizwa ze-INSTI ezi-
- Isentress (ratelgravir)
- ITivicay (dolutegravir)
- Vitekta (elvitegravir)
- I-Triumeq (dolutegravir + abacavir + lamivudine)
- Stribild (elvitegravir + cobicistat + tenofovir + emtricitabine)
- UGenvoya (elvitegravir + cobicistat + i-tenofovir AF + emtricitabine)
Nangona i-integrase inxube yeziyobisi, i-Dutrebis (ratelgravir + lamivudine), iphinde ivunyiwe yi-US Food and Drug Administration, ayifumanekanga kwi-US okwangoku.
Abavelisi bamachiza i-ViiV kunye neJanssen Pharmaceuticals njengamanje bebambisana kwelinye idiza edibeneyo eya kudibanisa i-dolutegravir kunye neziyobisi ezi- Edurant (rilpilvirine) . Omnye othembisa umgqatswa we-INSTI, i-cabotegravir, uhamba novavanyo lwesiganeko se-Phase III.
Njengeklasi yamachiza, i-integrase inhibitors ithathwa njengenzuzo ekuphatheni intsholongwane kaGawulayo, kunye neemfuno zokuthatha i-dosing elula, imiphumo emibini engaphantsi, iiprofayili zokuchasana nokuphucula.
Ngaloo ndlela, ii-INSTIs zikwahlula phakathi kwezikhetho zonyango ezikhethiweyo kwizikhokelo ezininzi ze-HIV, kubandakanywa ne-US
Ukhokelo lwangoku oluvela kwiSebe lezeMpilo laseMelika kunye neeNkonzo zoLuntu lubeka i-integrase inhibitors njengento ekhethiweyo, i-arhente yokuqala yabantu abasanda kuphathwa nge-HIV. Enyanisweni, kwindlela ezithandathu zonyango ezicetyiswayo ngoku zilungiselelwe izigulane ezisandul 'ukunyangwa, ezi zintlanu ziqulethe i-integrase inhibitor njengegosa labo lonyango.
I-Intergrase Workhibitors Work?
I-HIV idibanisa i-genome yentsholongwane ye-viral kwi-DNA yeseli yesithatha kwiinkqubo ezintlanu:
- I-enzyme ye-integrase ibophezela kwi-DNA ye-HIV, ekugqibeleni kwayo idalwe kwinkqubo ebizwa ngokuthi i- reverse transcription .
- I-DNA ye-HIV ikulungele ukudibanisa kwinkqubo ebizwa ngokuthi i- cleaving, ecacisa ngokucacileyo umgca we-viral genetic, ebeka izikhala ezivulekile kwisakhiwo sayo.
- I-strand edibeneyo ifakwa kwi-nucleus yeseli yesistim ngokusebenzisa i- pore yenyukliya .
- Xa sele ungaphakathi kwisucleus, i-DNA ye-HIV idluliselwa kwi-DNA ye-host in okubizwa ngokuba yi- strand transfer response. Kule nqanaba, i-DNA ye-viral ihlasela i-DNA yeseli yesigidi, ihlukanisa iimbophelelo ezibamba i-DNA kunye kunye nokuzibandakanya ngokwazo ngeemichiza ze-chemical DNA.
- Uhlaselo luya kuvuselela impendulo yokukhusela yemvelo ebizwa ngokuthi ukulungiswa kwe-gap , apho isalathisi esisisigxina iya kulungiswa ngokuzenzekelayo nayiphi na umonakalo kwi-DNA, ngokubalulekileyo ukuququzelela ukutshatyalaliswa kwendlela yokugcina i-genetic coding.
Ngokulula ngokuthintela i-enzyme ye-integrase, yonke inkqubo yokuhlanganiswa imisiwe, iphelile ngokugqibeleleyo umjikelezo wobomi. Nangona kunjalo, njengoko ukuhlanganiswa kukuphela kwesigaba esithile semigudu yobomi be-HIV, ezinye iziyobisi zithathwa ukuze zivimbele ezinye izigaba, ukukhusela ngakumbi i-HIV ekuphenduleni nokuqinisekisa ukuba umsebenzi wegciwane le-viral ukhutshiwe ngokupheleleyo (njengoko kulinganiswa nomthwalo wentsholongwane kaGawulayo).
Iimpembelelo ezisemacaleni kunye nokuqwalasela
Ngokungafani nezinye iiklasi ze-HIV, i-integrase inhibitors isebenza ngokuthe ngqo kwiindlela zentsholongwane ngokwabo kunokuba iiseli. Ngaloo ndlela, bathambekele ekubeni nefuthe elincinci elincinane, ngokukhawuleza uhudo, isisongulu, ukukhathala, intloko, kunye nokulala.
Uninzi lweziphumo zecala, nangona kunjalo, zixesha elide kwaye zivame ukuzixazulula zodwa. Xa kuthethwa oko, ukuba ufumana nayiphi na isiganeko esibi xa uthabatha inhlanganisi yeziyobisi ye-integrase, cebisa ugqirha okanye iklinikhi ngokukhawuleza. Musa ukuyeka unyango ngaphandle kokuthetha nochwepheshe oqeqeshiwe. Ukuyeka nokutshintsha kwangaphambili kunokukwenza okubi ngaphezu kokulungileyo.
Ngokufanayo, ngelixa i-integrase inhibitors ingenakunqwenela ukuxhatshazwa kwezidakamizwa ngaphambi kwexesha , kufuneka uphephe ukulahla kwamanani okanye ikhefu ekhatyweni. Ukuchasana kwenzeka xa amayeza egazi eqala ukuwa, avumela iintsholongwane eziguquguqukayo ukuba zivele kwaye ziqhubeke. Xa oku kwenzeka, iziyobisi zakho aziyi kukwazi ukusebenza kunye nangaphambili kwaye, ngamanye amaxesha, ziyakwazi.
Ekubeni i-integrase inhibitors ihlala egazini legazi ixesha elide, iyakwazi ukunqanda ukuguqulwa kwe-HIV nangona amaxesha athathwe. Kodwa kubalulekile ukuqonda ukuba ukuphazamiseka okude kunokugula kwaye ukunyanzelana kwansuku zonke kuyinto ebalulekileyo kwimpumelelo yonyango.
Imithombo:
US Administration and Drug Administration (FDA). Iphakheji yokuVunywa kweMithi - Igama leMilo: i-Isentress (ratelgravir) i-400mg Tablets. " Silver Spring, eMaryn; Oktobha 12, 2007.
ISizwe lesiZwe soMbane kunye neZifo ezithintekayo (iNIAID) "Uphuhliso lwe-HIV / AIDS oluPhambili lweMithi." EBethesda, eMaryn; hlaziywa ngoJulayi 21, 2015.
ISebe lezeMpilo kunye neNkonzo zoLuntu (DHHS). "Izikhokelo zokusetyenziswa kwee-Antiretroviral Agents kwi-HIV-1-abadala nabachaphazelekayo." Rockville, Maryland; hlaziywa ngoJanuwari 28, 2017; fi kelele kuMatshi 24, 2017.
Craigie, R. noBushman, F. "I-HIV DNA Integration". I-Cold Spring Harbour Perspectives kwiMithi. Julayi 2012; 2 (7): a006890.
Bushman, F .; Fujiwara, D .; kunye noCraigie, R. "Ukuhlanganiswa kwe-DNA ye-Retroviral ehambelana neprotheni yokuhlanganiswa kwe-HIV in vitro." Isayensi. NgoSeptemba 28, 1990; 249 (4976): 1555-1558.