Iimvumi zeNveli zivimbela i-HIV yokungena nokuthelela iiseli
I-inhibitors yokungena nge-HIV (eyaziwa nangokuthi i-fusion inhibitors) yiklasi le-drug antiretroviral esetyenziswe ekuphatheni i- HIV . Ama-molecule asebenzayo yeziyobisi anako ukuyeka i-HIV ukuba iphindwe ngokuzibandakanya ngokwabo kwiiprotheni ezithile kwi-cell. Ezi zi-proteins ezenza i-HIV ifune "ukuvula" ukuze ungene kwiseli. Ngaphandle kwendlela yokwenza njalo, i-HIV ayikwazi ukuphindaphinda iphinde idale ikopi ezininzi.
Abantu abachasene nezinye iiklasi ze-HIV banokungenelwa kwii-inhibitors zokungena njengoko banokutshintsha ngokutsha ukuguqulwa kwe-HIV ezingenakusetyenziswa kweziyobisi. Le nto iindaba ezilungileyo kakhulu kunoma ubani oye unyango iminyaka kwaye ufumene ngokweenketho ezimbalwa kunye nonyango.
Okwangoku, kukho inhibitors ezimbini zokungena kwe-HIV ezivunyiweyo yi-US Food and Drug Administration (FDA): i-Selzentry (maraviroc) ne-Fuzeon (enfuvirtide).
I-Maraviroc kunye neCCR5 I-Recepter Antagonists
I-CCR5 yamkeli ye-receptor yintlobo yokungena kwi-inhibitor evimbela i-HIV ukuba ibophe kwiprotein kwi-CD4 T-cell ebizwa ngeCCR5. I-CCR5 receptor yenye yeengongoma zokungena kwi-HIV, ngokukodwa kwintsholongwane yokuqala. Ngokuthintela oku kufakelwa, i-HIV ayikwazi ukungena kumphathi kwaye ihlasele umbane wayo.
Eyaziwa nangokuthi i- inhibitor yokungena , i-CCR5 yamkeli ye-receptor ihluke kwezinye iiklasi ze-antiretrovirals ngokungenakujoliswa kwintsholongwane ngqo kodwa kunoko idibanisa kumphezulu weseli yamkeli.
Kwaye kwahluke ngendlela ekunceda ngayo abanye abantu kungekhona abanye. Oku kungenxa yokuba i-HIV ingahluka ukusuka kumntu ukuya kwenye. Ezinye iintlobo ze-HIV ziya kubophelela kumsingatha usebenzisa i-receptor ye-CCR5; abanye baya kusebenzisa oko kuthiwa yi-CXCR4 receptor yokungena.
(Ngokuqhelekileyo, iCCR5 ibonakala ngakumbi kwiintsholongwane zakuqala ngexesha i-CXCR4 ibonwa kwisifo esilandelayo.)
Ukuqaphela oku, oogqirha baya kusebenzisa uvavanyo lofuzo olubizwa ngokuba yi-troyay assay luqinisekisa ubungqina be-tropism (i-orientation) ye-virus yakho ethile. Ukuba uvavanyo luhle kwiCCR5, intsholongwane kuthiwa yi "CCR5 iTroic," oku kuthetha ukuba iya kuphendula kwisicatshulwa seCCR5. Ngokwahlukileyo, igciwane le-CXCR4-tropicic ayiyi kuchatshazelwa yichiza.
Nangona iqela le-CCR5 liye laphuhliswa linye kuphela liye lafikelela kwiimarike:
- I-Aplaviroc (igama lekhowudi GSK-873140) lehlile ngexesha leemvavanyo zonyango ngo-2005 njengokuba kubangelwa yimichiza enobuthi.
- I-Maraviroc (ekhoyo phantsi kwegama lomnxeba uSelententry e-US neCelsentri phesheya) yavunywa ngo-Matshi 2007 ukuze isetyenziswe kwisigulane esaphathwa ngaphambili
- I-Vicriviroc (igama lekhowudi SCH 417690) lashiywa ngumenzi ngo-2010 emva kokuhluleka ukuhlangabezana neethagethi zokusebenza ezibekwa ngumenzi.
Esinye isilwanyana esivunyiweyo, ama-maraviroc, saboniswa ukufezekisa ngokupheleleyo intsholongwane kwi-60 ekhulwini labantu abachasene kakhulu nezinye iziyobisi ze-HIV. Abantu abakwiziyobisi kufuneka bajongwe ngokukhawuleza njengoko kungabangela ubuthi obunzulu besibindi kwezinye. Abanye bafumana ukukhawuleza kwesikhumba kunye nezinye iimpendulo.
I-Fuzeon kunye noPhuhliso lwee-Inhibitors ze-Fusion
Ukuxuba kuyinqanaba lobomi bentsholongwane kaGawulayo eyenza ukuba intsholongwane ibophe kwisitokethi esiphezulu ngaphambi kokungena kuyo.
I-fusion inhibitor isebenza ngokubophelela kwiprotheni ye-gp41 phezu kwendawo yeseli yesistim kwaye ikukhusele ukuba ingaxubeki ne-HIV. Ngaphandle kwalolu fusion, ukuphindaphinda kwe-HIV kumisiwe kwaye ukhuseleko luyacinywa.
Okwangoku, i-fusion inhibitors yenzelwe ukuhanjiswa ngejoyiki kunokuba itywala yomlomo. Oku kudibene neendleko eziphezulu zonyango (malunga nama-25,000 / ngonyaka), ziye zacutha ukusetyenziswa kweziyobisi ekuncediseni unyango (xa zonke ezinye iindlela zonyango ziphelile).
Kuye kwaphuhliswa abaviwa abaninzi befusion inhibitor, nangona kuphela oye wafika kwindawo yokuthengisa:
- I-Enfurvitide (efumaneka phantsi kwegama legama elithi Fuzeon) yavunywa yi-FDA ngo-2003 ukuze isebenzise kwizigulane ezinezonyango.
- I-T-1249 inqanyulwe ngumenzi ngenxa yenxalenye ekuphenduleni i-Fuzeon.
- I-TRI-1144 kunye ne-TRI-199 bobabini baye bathuthuka ukususela ngo-2003 kwaye abangeke bangene kwizilingo ezinkulu zeeklinikhi.
I-fusion inhibitor evunyelweyo, i-enfurvitide, idinga kabini-injection yansuku zonke. Imiphumo emibi ingabandakanya ukungabikho, ukungabandezeleka, ukuxinezeleka, ukukhwehlela, ukuxubusha kwintsholongwane, ukuphefumula okufutshane, ukulahleka kwesisindo, kunye nokuqina kolukhuseleko kwisiza sokungena.
Imithombo:
Biswas, P .; Tambussi, G .; kunye neLazzarin, A. "Ukufikelela kungenakuphikiswa? Ubume be-co-receptor inhibition yokulwa ne-HIV." Umbono woLwazi kwi-Pharmacotherapy. 2008; 8 (7): 923-933.
Ukutya kunye noLawulo lweeDrug (FDA). "I-FDA ivumela iNew Antiretroviral Drug." Silver Spring, eMaryn; Agasti 6, 2007.
FDA. Iphakheji yokuVunywa kweMithi: i-Fuzeon (enfuvirtide) yejoza. " Matshi 13, 2003.