Hoạt hóa miễn dịch & Viêm trong nhiễm HIV

TH THE HI NGH KHOA HC QUC GIA V PHềNG, NATIONAL SCIENTIFIC CONFERENCE ON HIV/AIDS CHNG HIV/AIDS LN TH Hot húa dch & Viờm nhim HIV Laurence WEISS Cỏc thay i sm nhim HIV cp tớnh Ti lng virus T bo T CD8 c hiu HIV CD4 (mỏu) Cỏc im mc (Tiờn lng tin trin) Hot húa dch núi chung T bo cú trớ nh dch CD4+ CCR5+ 2-3 tun 3-10 tun Nhim cp tớnh > thỏng Nhim mn tớnh Virus vo c th & nhõn lờn Viờm & hot húa dch CRP IL-6 Haptoglobin Acid glycoprotein 1- APP Min dch t Hot húa cỏc t bo nhiờn mono/M , DCs, NK Min dch thu c HIV Cỏc virus khỏc (CMV, HCV ) Sn phm ca vi khun(LPS) National Hot húaThet6 bo T Scientific Conference on HIV/AIDS th Bóo Cytokine sau nhim HIV Theo Mc Michael - Nat Rev Immunol 2010 The 6th National Scientific Conference on HIV/AIDS T bo T v cỏc im mc hot húa dch t nhiờn giai on nhim HIV sm d oỏn s gim t bo CD4 sau ú 68 ngi ln nhim HIV gn õy trc ART T l CD4 > 350 im mc hot húa t bo T CD8 CD38-MFI Trờn t bo T CD8 Thi gian (tun) Thi gian t bo CD4 350 c phõn ngu nhiờn vo nhúm giỏn on ART (DC) da vo tiờu CD4 so vi nhúm iu tr ART liờn tc (VS) Cỏc nguyờn nhõn gõy t vong ph bin nht: bnh ỏc tớnh khụng phi AIDS, CVD IL-6, hsCRP v D-dimer thi im ban u cú tng quan vi t vong mi nguyờn nhõn IL-6, D-dimer v hsCRP thi im ban u: liờn quan Kuller Plos Medicine 2008 Rodger JID 2008 rừ rngPlosOne vi CVD Duprez 2012 PHIDISA (Nam Phi), tng mc tin ART ca hsCRP, IL-6 v D-dimer: tng quan cht ch vi t l t vong sm sau bt u ART Ledwaba, PlosOne 2012 The 6th National Scientific Conference on HIV/AIDS nh hng ca ART i vi tin s t nhiờn ca nhim HIV The 6th National Scientific Conference on HIV/AIDS S tn ti ca hot húa t bo T nhim mn tớnh nhng bnh nhõn c iu tr ART n = 30 HIV+ cú CV < 75 c/mL The National Scientific Conference on HIV/AIDS th Hunt, JID, 2003 Hunt, JID 2008 Mc dự cú hin tng c ch lõu di virus nhng cỏc du n sinh hc dng hũa tan ca viờm cao hn nhúm bnh nhõn so vi qun th dõn s núi chung The 6th National Scientific Conference on HIV/AIDS Neuhaus JID 2010 Mc sCD14 huyt tng: yu t d oỏn t l t vong c lp nghiờn cu SMART Thit k nghiờn cu bnh-chng Nested ca nghiờn cu SMART 74 DCs + 120 CV + 100 AIDS (20 NA) / N= 5472 ca chng/1 ca bnh Hu ht cỏc bnh nhõn iu tr Art u cú ti lng virus < 400 bn sao/mL sCD14, IFABP, LPS, EndoCAB huyt ti thi im ban u SCD14: du n ca hot húa t bo n nhõn (protein ca giai on cp tớnh) khụng phi l yu t ch th cn thit ca chuyn v vi sinh vt The 6th National Scientific Conference on HIV/AIDS Sandler, JID 2011 Viờm cựng vi s nhõn lờn Viờm liờn tc ca virus iu tr ART T bo n nhõn Min Min dch thu dch t nhiờn c pDCs NK The 6th National Scientific Conference on HIV/AIDS Viờm Kim soỏt HIV NHIM VIRUS MN TNH (HIV) UNG TH Viờm Cỏc bnh tim mch Cỏc ri lon nhn thc Loóng xng The 6th National Scientific Conference on HIV/AIDS Viờm d oỏn c bnh nhim HIV c iu tr, ging nh qun th bỡnh thng T l t vong (Kuller, PLoS Med, 2008, Sandler JID 2011, Tien JAIDS 2011) Bnh tim mch (Baker, CROI 2013) U lympho (Breen, Cancer Epi Bio Prev, 2010) Huyt tnh mch (Musselwhite, AIDS, 2011) Tiu ng tớp II (Brown, Diabetes Care, 2010) Ri lon chc nng nhn thc (Burdo AIDS 2012) Tỡnh trng yu ui (Erlandson, JID 2013) The 6th National Scientific Conference on HIV/AIDS Cỏc du n hũa tan ca viờm & ụng mỏu, ch khụng phi l hot húa t bo T d oỏn c cỏc hin tng xỏc nh khụng phi AIDS quỏ trỡnh iu tr c ch bng ART Nghiờn cu Bnh-Chng trờn cỏc i tng ALLRT (nghiờn cu ACTG) (cha iu tr ART BL v c ch bng ART quỏ trỡnh FU) Ca bnh: t vong khụng phi AIDS, MI, t qu, ung th khụng phi AIDS, hoc cỏc nhim trựng nng vi khun khụng liờn quan n AIDS Ca chng (2 ca chng/ca bnh) Thay i CD4 nhiu hn nm cú liờn quan ti gim nguy c i vi cỏc s kin khụng liờn quan n AIDS (T sut chờnh (OR) 100 t bo tng lờn = 0.81, p= 0.007) Hot húa t bo T cao: tng quan khụng nht quỏn vi mt s kin khụng phi AIDS IL-6,sCD14, sTNFR-I, sTNFR-II, v D-dimer cao hn trc s dng ART tng quan c lp vi cac s kin khụng phi AIDS The 6th National Scientific Conference on HIV/AIDS Tenorio CROI 2013 Cỏc du n hũa tan ca viờm & ụng mỏu, ch khụng phi l hot húa t bo T d oỏn c cỏc hin tng xỏc nh khụng phi AIDS quỏ trỡnh iu tr c ch bng ART Nghiờn cu Bnh-Chng trờn cỏc i tng ALLRT (nghiờn cu ACTG) (cha iu tr ART BL v c ch bng ART quỏ trỡnh FU) Ca bnh: t vong khụng phi AIDS, MI, t qu, ung th khụng phi AIDS, hoc cỏc nhim trựng nng vi khun khụng liờn quan n AIDS Ca chng (2 ca chng/ca bnh) Thay i CD4 nhiu hn nm cú liờn quan ti gim nguy c i vi cỏc s kin khụng liờn quan n AIDS (T sut chờnh (OR) 100 t bo tng lờn = 0.81, p= 0.007) Hot húa t bo T cao: tng quan khụng nht quỏn vi mt s kin khụng phi AIDS IL-6,sCD14, sTNFR-I, sTNFR-II, v D-dimer cao hn trc s dng ART tng quan c lp vi cac s kin khụng phi AIDS The 6th National Scientific Conference on HIV/AIDS Tenorio CROI 2013 Vai trũ ca hot húa dch nhim HIV trỡ Klatt, Immunol rev 2013 Viờm trỡ iu tr ART Tng t bo T CD4 di mc ti u HIV trỡ Cỏc bnh i kốm (Tng x va ng mch, viờm ng mch, ri lon nhn thc, bnh thn mn tớnh, loóng xng: ôViờm-lóo húaằ , ung th) Nguy c t vong The 6th National Scientific Conference on HIV/AIDS Li cm n Bnh vin Europộen G Pompidou Christophe Piketty Maria Manea Erika Bourzam Bnh vin Saint-Antoine Pierre-Marie Girard Pauline Campa Nelly Desplanques Bnh vin Tenon Laurence Slama Gilles Pialoux U943 Dominique Costagliola Lambert Assoumou Mathieu Chevalier Gaởl Petitjean Cộline Didier Daniel Scott-Algara Franỗoise Barrộ-Sinoussi INSERM U 1018 Laurence Meyer Christiane Deveau Feriel Tibaoui CHU Carộmeau Nợmes Jean-Philippe Lavigne Catherine Dunyach EA 3620 Christine Rouzioux Nhúm nghiờn cu ANRS 116 SALTO Tt c bnh nhõn tham giaThe nhng nghiờn cu ny Conference on HIV/AIDS 6th National Scientific