Lithethefatsi Tse Matla tse Khethiloeng bakeng sa Phekolo ea Pele
Integrase inhibitors (e tsejoang hape e le integrase strand transfer inhibitors, kapa INSTIs) ke sehlopha se matla sa meriana e loantšang li-antiretroviral e thibelang HIV hore e kenye letsoho la liphatsa tsa lefutso (genome) ho DNA ea sele ea tšoaetso ea tšoaetso. E etsa joalo ka ho thibela enzyme e bitsoang integrase 'me, ka ho etsa joalo, e etsa hore ho se ke ha khoneha hore HIV e fetohe.
Isentress (ratelgravir) e bile eona ea pele INSTI e amoheloang ke US Food and Drug Administration (FDA) ka la 12 October, 2007.
Bohle bo bolelitsoe, hona joale ho na le limolek'hule tse tharo tsa lithethefatsi tsa INSTI tse amohelehang le meriana e mene e tsitsitseng e kopantseng lithethefatsi tseo INSTI e leng karolo ea eona
- Isentress (ratelgravir)
- Tivicay (dolutegravir)
- Vitekta (elvitegravir)
- Triumeq (dolutegravir + bacavir + lamivudine)
- Stribild (elvitegravir + cobicistat + tenofovir + emtricitabine)
- Genvoya (elvitegravir + cobicistat + tenofovir AF + emtricitabine)
Le hoja lithethefatsi tse kopaneng tsa integrase, Dutrebis (ratelgravir + lamivudine), le tsona li amoheloa ke US Food and Drug Administration, ha e fumaneha khoebong United States hona joale.
Bahlahisi ba lithethefatsi ViiV le Janssen Pharmaceuticals ba ntse ba sebelisana ka moriana o mong o kopantseng le dolutegravir le lithethefatsi Edurant (rilpilvirine) . Mokhethoa e mong ea tšepisitsoeng oa INSTI, cabotegravir, o ntse a hlaheloa ke liteko tsa batho ba Phase III.
Joaloka sehlopha sa lithethefatsi, integrase inhibitors e nkoa e le molemo bakeng sa ho phekola tšoaetso ea HIV, ka litlhoko tse fokolang tsa li-dosing, litla-morao tse fokolang, litlhaloso tse ntlafetseng tsa ho hanyetsa, le ho tsitsa haholoanyane.
Ka hona, li-INSTIs li aroloa e le har'a mekhoa ea phekolo e khethiloeng ka litsela tse ngata tsa HIV, ho akarelletsa le tsa US
Tataiso ea morao-rao e tsoang Lefapheng la Bophelo le Litšebeletso tsa Botho la United States e beha li-integrase inhibitors e le moemeli ea khethehileng oa batho ba sa tsoa tšoaroa bakeng sa HIV. Ha e le hantle, likhethong tse tšeletseng tsa phekolo tseo hona joale li khothalletsoang ho bakuli ba sa tsoa phekoloa, tse hlano li na le integrase inhibitor e le mokokotlo oa lithethefatsi.
Li-Inhibitor tsa Intergrase li Sebetsa Joang?
HIV e kopanya liphatsa tsa eona tsa kokoana-hloko ea 'mele ho DNA ea mohalali ka mehato e mehlano:
- Enzyme ea integrase e tlamella HIV DNA, eo qetellong ea eona e entsoeng ka ts'ebetso e bitsoang ho fetola phetolelo .
- Ka nako eo, HIV DNA e lokiselitsoe ho kenyelletswa ka mokhoa o bitsoang cleaving, e hlileng e fokolang likokoana-hloko tsa liphatsa tsa lefutso, e leng ho siea likheo tse bulehileng mohahong oa eona.
- The strand e khotsofalitsoeng e ntan'o kenngoa ka nucleus ea sele e amohelehang ka pore ea nyutlelie .
- Hang ha o kene ka hare ho nucleus, HIV DNA e fetisetsoa ho DNA e amohelehang ho eona ke seo ho thoeng ke mohala oa phetoho. Mothati ona, likokoana-hloko tsa DNA li hlasela DNA ea sele e amohelehang ka ho toba, e arola likarolo tse tšoereng DNA hammoho le ho itlama ka lik'hemik'hale tsa likokoana-hloko tsa DNA.
- Hona tlhaselo e etsa hore ho be le karabo ea tšireletso ea tlhaho e bitsoang ho lokisa likhase , moo sele e amohelang e tla lokisa tšenyo leha e le efe DNA, e leng ho thusang ho nkoa ha li-genetic coding.
Ka feela ka ho thibela enzyme ea integrase, ts'ebetso eohle ea ho ikopanya e emisoa, ka ho felisa phetoho ea bophelo. Leha ho le joalo, ha kopano e le 'ngoe feela ea mekhahlelo e mengata ea bophelo ba HIV, lithethefatsi tse ling li nkoa e le ho thibela mehato e meng, ho thibela HIV hore e se ke ea pheta-pheta le ho etsa bonnete ba hore tšebetso ea kokoana-hloko e thibetsoe ka ho feletseng (e lekanngoa le tšoaetso ea kokoana-hloko ea HIV).
Litla-morao le Mehopolo
Ho fapana le lihlopha tse ling tsa kokoana-hloko ea HIV, integrase inhibitors e sebetsa ka ho toba mekhoeng ea likokoana-hloko ka boeona ho e-na le liseleng. Ka lebaka leo, ba atisa ho ba le phello e fokolang haholo, haholo-holo letšollo, ho nyeheloa ke pelo, mokhathala, ho kula le ho hlobaela.
Boholo ba litla-morao tsena, leha ho le joalo, ke nakoana 'me hangata bo rarolla ka bobona. Ha ho buuoa joalo, haeba u e-ba le ketsahalo efe kapa efe e bohloko ha u nka motsoako oa intrase inhibitor, u eletsa ngaka kapa kliniki hang-hang. U se ke ua emisa phekolo ntle le bonyane ho bua le setsebi se hloahloa. Ho emisa le ho fetoha pele ho nako ho ka ntša kotsi ho feta molemo.
Ka mokhoa o ts'oanang, le hoja integrase inhibitors e se e le monyetla oa ho hanyetsa lithethefatsi pele ho nako , u lokela ho qoba litekanyo kapa likheo tse sa hlokahaleng kalafo. Khahlano e etsahala ha maemo a lithethefatsi maling a qala ho oa, e leng ho lumellang likokoana-hloko tsa 'mele hore li hlahe le ho ata. Ha sena se etsahala, lithethefatsi tsa hau li ke ke tsa khona ho sebetsana hantle le pele le hore maemong a mang li ka hlōleha.
Kaha integrase inhibitors e ntse e le ka nako ea nako e telele, li khona ho thibela li-mutants tsa HIV esita le ha meriana e sa hlokomeloe. Empa ke habohlokoa ho utloisisa hore ho senyeha ha nako e telele ho sa ele hloko le hore ts'ebeliso ea letsatsi le leng le le leng e lule e le senotlolo sa katleho ea phekolo.
Lisebelisoa:
US Administration of Drug and Drug Administration (FDA). "Phaketeng ea Tšebeliso ea Lithethefatsi - Lebitso la Meriana: Isentress (ratelgravir) Matlapa a 400mg." Silver Spring, Maryland; La 12 October, 2007.
Setsi sa Sechaba sa Mafu le Matšoao a Ts'oaetsanoang (NIAID) "Ntlafatso ea Meriana ea HIV le AIDS." Bethesda, Maryland; e ntlafalitsoeng ka la 21 July, 2015.
Lefapha la Bophelo le Litšebeletso tsa Botho (DHHS). "Tataiso ea Tšebeliso ea Basebetsi ba Antiretroviral bathong ba nang le HIV-1-ba nang le tšoaetso le bacha." Rockville, Maryland; e ntlafalitsoeng ka la 28 January, 2017; e fihlile ka la 24 March, 2017.
Craigie, R. le Bushman, F. "HIV DNA Integration." Sekepe sa Cold Spring Sepheo sa Meriana. July 2012; 2 (7): a006890.
Bushman, F .; Fujiwara, D .; le Craigie, R. "Phetoho ea DNA ea Retroviral e tsamaisoang ke protheine ea ho kopanya HIV." Saense. La 28 September, 1990; 249 (4976): 1555-1558.