Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.

,P Mugyenyi,A S Walker,J Hakim,P Munderi,D M Gibb,C Kityo,A Reid,H Grosskurth,J H Darbyshire,F Ssali, D Bray,E Katabira,A G Babiker,C F Gilks, H Grosskurth, P Munderi,G Kabuye,D Nsibambi,R Kasirye,E Zalwango, M Nakazibwe,B Kikaire, G Nassuna, R Massa,K Fadhiru, M Namyalo, A Zalwango, L Generous,P Khauka, N Rutikarayo, W Nakahima,A Mugisha,J Todd,J Levin, S Muyingo,A Ruberantwari,P Kaleebu,D Yirrell,N Ndembi,F Lyagoba,P Hughes,M Aber,A Medina Lara, S Foster,J Amurwon,B Nyanzi Wakholi,J Whitworth, K Wangati,B Amuron, D Kajungu,J Nakiyingi, W Omony, K Fadhiru, D Nsibambi, P Khauka, P Mugyenyi, C Kityo, F Ssali,D Tumukunde, T Otim,J Kabanda,H Musana,J Akao,H Kyomugisha,A Byamukama, J Sabiiti, J Komugyena,P Wavamunno, S Mukiibi, A Drasiku,R Byaruhanga, O Labeja,P Katundu,S Tugume, P Awio, A Namazzi,G T Bakeinyaga, H Katabira, D Abaine, J Tukamushaba, W Anywar, W Ojiambo, E Angweng,S Murungi, W Haguma, S Atwiine,J Kigozi,L Namale, A Mukose, G Mulindwa, D Atwiine, A Muhwezi, E Nimwesiga, G Barungi, J Takubwa, S Murungi, D Mwebesa,G Kagina, M Mulindwa, F Ahimbisibwe, P Mwesigwa, S Akuma, C Zawedde, D Nyiraguhirwa, C Tumusiime, L Bagaya, W Namara, J Kigozi, J Karungi, R Kankunda, R Enzama, A Latif, J Hakim,V Robertson,A Reid,E Chidziva, R Bulaya-Tembo,G Musoro, F Taziwa,C Chimbetete,L Chakonza, A Mawora,C Muvirimi, G Tinago, P Svovanapasis,M Simango,O Chirema,J Machingura,S Mutsai,M Phiri, T Bafana,M Chirara,L Muchabaiwa,M Muzambi, J Mutowo, T Chivhunga, E Chigwedere, M Pascoe, C Warambwa, E Zengeza, F Mapinge, S Makota, A Jamu, N Ngorima, H Chirairo, S Chitsungo, J Chimanzi, C Maweni, R Warara, M Matongo,S Mudzingwa, M Jangano, K Moyo, L Vere, N Mdege, I Machingura, E Katabira, A Ronald, A Kambungu,F Lutwama,I Mambule,A Nanfuka,J Walusimbi,E Nabankema,R Nalumenya, T Namuli, R Kulume, I Namata, L Nyachwo,A Florence, A Kusiima,E Lubwama, R Nairuba, F Oketta, E Buluma, R Waita,H Ojiambo, F Sadik,J Wanyama, P Nabongo, J Oyugi, F Sematala,A Muganzi,C Twijukye, H Byakwaga, R Ochai, D Muhweezi,A Coutinho, B Etukoit, C Gilks, K Boocock, C Puddephatt,C Grundy,J Bohannon, D Winogron, D M Gibb, A Burke, D Bray,A Babiker, A S Walker,H Wilkes,M Rauchenberger,S Sheehan, C Spencer-Drake, K Taylor,M Spyer,A Ferrier,B Naidoo,D Dunn,R Goodall, J H Darbyshire, L Peto, R Nanfuka, C Mufuka-Kapuya, P Kaleebu,D Pillay, V Robertson, D Yirrell, S Tugume, M Chirara, P Katundu, N Ndembi, F Lyagoba, D Dunn, R Goodall,A McCormick, A Medina Lara, S Foster, J Amurwon, B Nyanzi Wakholi, J Kigozi, L Muchabaiwa, M Muzambi,I Weller, A Babiker, S Bahendeka, M Bassett,A Chogo Wapakhabulo, J H Darbyshire,B Gazzard, C Gilks, H Grosskurth, J Hakim, A Latif, C Mapuchere,O Mugurungi, P Mugyenyi, C Burke, S Jones, C Newland, G Pearce, S Rahim,J Rooney, M Smith,W Snowden, J-M Steens,A Breckenridge,A McLaren, C Hill,J Matenga,A Pozniak,D Serwadda,T Peto,A Palfreeman,M Borok, E Katabira

LANCET（2009）

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摘要

BACKGROUND:HIV antiretroviral therapy (ART) is often managed without routine laboratory monitoring in Africa; however, the effect of this approach is unknown. This trial investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving ART had an important long-term effect on clinical outcomes in Africa. METHODS:In this open, non-inferiority trial in three centres in Uganda and one in Zimbabwe, 3321 symptomatic, ART-naive, HIV-infected adults with CD4 counts less than 200 cells per microL starting ART were randomly assigned to laboratory and clinical monitoring (LCM; n=1659) or clinically driven monitoring (CDM; n=1662) by a computer-generated list. Haematology, biochemistry, and CD4-cell counts were done every 12 weeks. In the LCM group, results were available to clinicians; in the CDM group, results (apart from CD4-cell count) could be requested if clinically indicated and grade 4 toxicities were available. Participants switched to second-line ART after new or recurrent WHO stage 4 events in both groups, or CD4 count less than 100 cells per microL (LCM only). Co-primary endpoints were new WHO stage 4 HIV events or death, and serious adverse events. Non-inferiority was defined as the upper 95% confidence limit for the hazard ratio (HR) for new WHO stage 4 events or death being no greater than 1.18. Analyses were by intention to treat. This study is registered, number ISRCTN13968779. FINDINGS:Two participants assigned to CDM and three to LCM were excluded from analyses. 5-year survival was 87% (95% CI 85-88) in the CDM group and 90% (88-91) in the LCM group, and 122 (7%) and 112 (7%) participants, respectively, were lost to follow-up over median 4.9 years' follow-up. 459 (28%) participants receiving CDM versus 356 (21%) LCM had a new WHO stage 4 event or died (6.94 [95% CI 6.33-7.60] vs 5.24 [4.72-5.81] per 100 person-years; absolute difference 1.70 per 100 person-years [0.87-2.54]; HR 1.31 [1.14-1.51]; p=0.0001). Differences in disease progression occurred from the third year on ART, whereas higher rates of switch to second-line treatment occurred in LCM from the second year. 283 (17%) participants receiving CDM versus 260 (16%) LCM had a new serious adverse event (HR 1.12 [0.94-1.32]; p=0.19), with anaemia the most common (76 vs 61 cases). INTERPRETATION:ART can be delivered safely without routine laboratory monitoring for toxic effects, but differences in disease progression suggest a role for monitoring of CD4-cell count from the second year of ART to guide the switch to second-line treatment. FUNDING:UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories.

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viral load,glomerular filtration rate

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