Izidakamizwa zamanoveli zivimbela i-HIV ukungena nokutheleleka amaseli
I-HIV yokungena inhibitors (eyaziwa nangokuthi i-fusion inhibitors) iyisigaba semithi elwa nezidambisigciwane esetshenziselwa ukuphatha i- HIV . Ama-molecule asebenzayo alo muthi akwazi ukuvimbela igciwane lesandulela ngculaza ukuba lingeneli ngokuzihlanganisa neziqu ezithile ezisekhanda. Lawa amaprotheni okuthi i-HIV idinga "ukuvula" ukuze ufake iseli. Ngaphandle kwendlela yokwenza kanjalo, i-HIV ayikwazi ukuphindaphinda iphinde idale amakhophi amaningi.
Abantu abaphikisana nezinye izigaba zemithi ye-HIV bangase bazuze ekungeneni kwe-inhibitors njengoba bengakwazi ukunqoba ukuguqulwa kwe-HIV okunganqamuki kwezidakamizwa. Lezi zindaba ezinhle kakhulu kunoma ubani oye waphatha ukwelashwa iminyaka futhi uzitholile ngezinketho zokwelashwa ezimbalwa futhi ezimbalwa.
Njengamanje, kunama-inhibitors amabili okungenwa yi-HIV avunywe yi-US Food and Drug Administration (FDA): i-Selzentry (maraviroc) ne-Fuzeon (enfuvirtide).
I-Maraviroc ne-CCR5 Receptor Antagonists
Umphikisi we-CCR5 wokutholwa yi-type inhibitor yokungena okuvimbela igciwane lesandulela ngculazi ukuba libophezele kumaprotheni ku-CD4 T-cell ebizwa nge-CCR5. I-CCR5 receptor ingenye yezinto eziyinhloko zokungena nge-HIV, ikakhulukazi ekutheleleni kwesandulela-ngculaza. Ngokuvimbela lokhu okunamathiselweyo, i-HIV ayikwazi ukungena kumphathi futhi ihlasele umshini wayo wezakhi zofuzo.
Eyaziwa nangokuthi i- inhibitor yokungena , umphikisi we-CCR5 we-receptor ophikisanayo uhlukile kwezinye izigaba zama-antiretrovirals uma engahlosisi igciwane ngqo kodwa esikhundleni salokho ufaka emkhakheni wesitoreji esiphezulu.
Ihluke kakhulu nokuthi ingazuza kanjani abanye abantu hhayi abanye. Lokhu kungenxa yokuthi i-HIV ingahluka kusuka komuntu kuya kwesinye. Ezinye izinhlobo ze-HIV ziyobopha kumuntu ophetheyo usebenzisa i-receptor ye-CCR5; abanye bazosebenzisa lokho okubizwa ngokuthi i-receptor ye-CXCR4 yokungena.
(Ngokuvamile, i-CCR5 ibonakala ngaphezulu ekutheleleni okuqala ngenkathi i-CXCR4 ibonakala kwisifo esilandelayo kamuva.)
Ukuze unqume lokhu, odokotela bazosebenzisa ukuhlolwa kofuzo okuthiwa i-trofile assay kuqinisekisa ukushisa (ukuqondisa) kwegciwane lakho eliqondile. Uma ukuhlolwa kulungile ku-CCR5, igciwane kuthiwa "i-CCR5 tropic," okusho ukuthi lizophendula kwisidakamizwa se-CCR5. Ngokuphambene, igciwane le-CXCR4-tropic ngeke liphazamiseke yilo muthi.
Ngenkathi iningi labaphikisi be-CCR5 lakhiwe kuphela kuphela elifinyelele emakethe:
- I-Aplaviroc (igama lekhodi le-GSK-873140) lehliwe ngesikhathi kuvivinyelwa emitholampilo ngo-2005 njengalokhu kubangelwa izidakamizwa ezinobindi.
- I-Maraviroc (etholakala ngaphansi kwegama lamagama eSelzentry e-US naseCelsentri phesheya) yamukelwa ngo-Mashi 2007 ukuze isetshenziswe kwisiguli esiphethwe ngaphambili
- I-Vicriviroc (igama lekhodi SCH 417690) lashiywa ngumkhiqizi ngo-2010 ngemuva kokuhluleka ukuhlangabezana nezinhloso zokusebenza ezibekwe umenzi.
Isidakamizwa esisodwa esivunyiwe, ama-maraviroc, saboniswa ukufeza ukupheliswa okuphelele kwegciwane kumaphesenti angu-60 abantu abaphikisana kakhulu nezinye izidakamizwa ze-HIV. Abantu abadinga izidakamizwa kumele baqashwe ngokucophelela njengoba kungabangela ubuthi obunzulu besibindi kwabanye. Abanye bangase babone ukuqhuma kwesikhumba kanye nokunye ukubhekana nokugula.
I-Fuzeon neNtuthuko ye-Fusion Inhibitors
I-Fusion iyisiteji emjikelezweni wokuphila we-HIV okwenza igciwane libophe esitokisini esiphezulu ngaphambi kokungena kulo.
I-inhibitor ye-fusion isebenza ngokubopha iphrotheni ye-gp41 ebusweni besitokisi esiphezulu futhi iyivimbele ekuhlanganyeleni ne-HIV. Ngaphandle kwalokhu kuhlanganiswa, ukuphindaphinda kwe-HIV kumisiwe futhi ukutheleleka kuvinjelwe.
Okwamanje, inhibitors ye-fusion iklanyelwe ukuhanjiswa ngomjovo kunokuba isidakamizwa somlomo. Lokhu, kuhlangene nezindleko eziphezulu zokwelashwa (cishe u-$ 25,000 / ngonyaka), kunqunyelwe ukusetshenziswa kwezidakamizwa ekunakekeleni ukwelashwa (lapho zonke ezinye izinketho zokwelapha seziphelile).
Kuye kwaqalwa ukhetho oluningi lwe-fusion inhibitor, nakuba eyodwa kuphela efinyelele emakethe:
- I-Enfurvitide (itholakale ngaphansi kwegama elithi Fuzeon) yamukelwa yi-FDA ngo-2003 ukuze isetshenziswe kwiziguli ezikwazi ukuthola ukwelashwa.
- I-T-1249 inqanyuliwe ngumenzi ngenxa yokuthi iyingxenye yokuphendula okungapheli ku-Fuzeon.
- I-TRI-1144 kanye ne-TRI-199 bobabili babelokhu bethuthukile kusukela ngo-2003 futhi abangeke bangene ezivivinyweni ezinkulu zomtholampilo.
I-fusion inhibitor egunyaziwe, enfurvitide, idinga kabili-injection yansuku zonke. Imiphumela emibi ingabandakanya ukungalahleki, ubuhlungu be-muscle, ukucindezeleka, ukukhwehlela, ukukhipha isikhumba senhliziyo, ukuphefumula, ukulahlekelwa isisindo, nokuqina kesikhumba endaweni yomjovo.
Imithombo:
Biswas, P .; I-Tambussi, i-G .; kanye neLazzarin, A. "Ukufinyelela kunqatshelwe? Isimo sokubambisana kwe-co-receptor sokulwa nokungenwa kwe-HIV." I-Expert Opinion ku-Pharmacotherapy. 2008; 8 (7): 923-933.
Ukuphathwa Kwezokudla Nezidakamizwa (FDA). "I-FDA ivumela i-Antivelroviral Drug Novel." I-Silver Spring, e-Maryland; Agasti 6, 2007.
I-FDA. "Iphakheji Yokuvunyelwa Kwezidakamizwa: Fuzeon (enfuvirtide) yomjovo." Mashi 13, 2003.