Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.
Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.
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DOI：
10.1016/s0140-6736(09)62067-5
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发表时间：
2010-01-09
期刊：
影响因子：
168.9
通讯作者：
Muzambi, M.
中科院分区：
文献类型：
--
作者：
Mugyenyi, P.;Walker, A. S.;Hakim, J.;Munderi, P.;Gibb, D. M.;Kityo, C.;Reid, A.;Grosskurth, H.;Darbyshire, J. H.;Ssali, F.;Bray, D.;Katabira, E.;Babiker, A. G.;Gilks, C. F.;Grosskurth, H.;Munderi, P.;Kabuye, G.;Nsibambi, D.;Kasirye, R.;Zalwango, E.;Nakazibwe, M.;Kikaire, B.;Nassuna, G.;Massa, R.;Fadhiru, K.;Namyalo, M.;Zalwango, A.;Generous, L.;Khauka, P.;Rutikarayo, N.;Nakahima, W.;Mugisha, A.;Todd, J.;Levin, J.;Muyingo, S.;Ruberantwari, A.;Kaleebu, P.;Yirrell, D.;Ndembi, N.;Lvagoba, F.;Hughes, P.;Aber, M.;Lara, A. Medina;Foster, S.;Amurwon, J.;Wakholi, B. Nyanzi;Whitworth, J.;Wangati, K.;Amuron, B.;Kajungu, D.;Nakiyingi, J.;Omony, W.;Fadhiru, K.;Nsibambi, D.;Khauka, P.;Mugyenyi, P.;Kityo, C.;Ssali, F.;Tumukunde, D.;Otim, T.;Kabanda, J.;Musana, H.;Akao, J.;Kyomugisha, H.;Byamukama, A.;Sabiiti, J.;Komugyena, J.;Wavamunno, P.;Mukiibi, S.;Drasiku, A.;Byaruhanga, R.;Labeja, O.;Katundu, P.;Tugume, S.;Awio, P.;Namazzi, A.;Bakeinyaga, G. T.;Katabira, H.;Abaine, D.;Tukamushaba, J.;Anywar, W.;Ojiambo, W.;Angweng, E.;Murungi, S.;Haguma, W.;Atwiine, S.;Kigozi, J.;Namale, L.;Mukose, A.;Mulindwa, G.;Atwiine, D.;Muhwezi, A.;Nimwesiga, E.;Barungi, G.;Takubwa, J.;Murungi, S.;Mwebesa, D.;Kagina, G.;Mulindwa, M.;Ahimbisibwe, F.;Mwesigwa, P.;Akuma, S.;Zawedde, C.;Nyiraguhirwa, D.;Tumusiime, C.;Bagaya, L.;Namara, W.;Kigozi, J.;Karungi, J.;Kankunda, R.;Enzama, R.;Latif, A.;Hakim, J.;Robertson, V.;Reid, A.;Chidziva, E.;Bulaya-Tembo, R.;Musoro, G.;Taziwa, F.;Chimbetete, C.;Chakonza, L.;Mawora, A.;Muvirimi, C.;Tinago, G.;Svovanapasis, P.;Simango, M.;Chirema, O.;Machingura, J.;Mutsai, S.;Phiri, M.;Bafana, T.;Chirara, M.;Muchabaiwa, L.;Muzambi, M.;Mutowo, J.;Chivhunga, T.;Chigwedere, E.;Pascoe, M.;Warambwa, C.;Zengeza, E.;Mapinge, F.;Makota, S.;Jamu, A.;Ngorima, N.;Chirairo, H.;Chitsungo, S.;Chimanzi, J.;Maweni, C.;Warara, R.;Matongo, M.;Mudzingwa, S.;Jangano, M.;Moyo, K.;Vere, L.;Mdege, N.;Machingura, I.;Katabira, E.;Ronald, A.;Kambungu, A.;Lutwama, F.;Mambule, I.;Nanfuka, A.;Walusimbi, J.;Nabankema, E.;Nalumenya, R.;Namuli, T.;Kulume, R.;Namata, I.;Nyachwo, L.;Florence, A.;Kusiima, A.;Lubwama, E.;Nairuba, R.;Oketta, F.;Buluma, E.;Waita, R.;Ojiambo, H.;Sadik, F.;Wanyama, J.;Nabongo, P.;Oyugi, J.;Sematala, F.;Muganzi, A.;Twijukye, C.;Byakwaga, H.;Ochai, R.;Muhweezi, D.;Coutinho, A.;Etukoit, B.;Gilks, C.;Boocock, K.;Puddephatt, C.;Grundy, C.;Bohannon, J.;Winogron, D.;Gibb, D. M.;Burke, A.;Bray, D.;Babiker, A.;Walker, A. S.;Wilkes, H.;Rauchenberger, M.;Sheehan, S.;Spencer-Drake, C.;Taylor, K.;Spyer, M.;Ferrier, A.;Naidoo, B.;Dunn, D.;Goodall, R.;Darbyshire, J. H.;Peto, L.;Nanfuka, R.;Mufuka-Kapuya, C.;Kaleebu, P.;Pillay, D.;Robertson, V.;Yirrell, D.;Tugume, S.;Chirara, M.;Katundu, P.;Ndembi, N.;Lyagoba, F.;Dunn, D.;Goodall, R.;McCormick, A.;Lara, A. Medina;Foster, S.;Amurwon, J.;Wakholi, B. Nyanzi;Kigozi, J.;Muchabaiwa, L.;Muzambi, M.
在非洲，艾滋病毒抗逆转录病毒治疗通常在没有常规实验室监测的情况下进行；然而，这种方法的效果尚不清楚。该试验调查了在非洲接受抗逆转录病毒治疗的艾滋病毒感染患者的常规毒性和疗效监测是否对临床结果具有重要的长期影响。在乌干达的三个中心和津巴布韦的一个中心进行的这项开放的、非低度性试验中，3321名有症状的、未经抗逆转录病毒治疗的hiv感染成人，CD4细胞计数低于每μL 200个细胞，开始抗逆转录病毒治疗，随机分配到实验室和临床监测（LCM, n=1659）或临床驱动监测（CDM, n=1662），由计算机生成列表。血液学、生物化学和cd4细胞计数每12周进行一次。在LCM组，临床医生可以获得结果；在CDM组中，如果有临床适应症和4级毒性，可以要求结果（除了cd4细胞计数）。两组参与者在新的或复发的世卫组织4期事件后，或CD4计数低于每μL 100个细胞（仅限LCM）后切换到二线抗逆转录病毒治疗。共同主要终点是新的世卫组织4期艾滋病毒事件或死亡，以及严重不良事件。非劣效性定义为新的WHO 4期事件或死亡的风险比（HR）的95%置信上限不大于1.18。分析的目的是治疗。本研究已注册，注册号为ISRCTN13968779。分配给CDM的两名参与者和分配给LCM的三名参与者被排除在分析之外。CDM组的5年生存率为87% (95% CI 85-88)， LCM组的5年生存率为90%(88-91)，在平均4.9年的随访中，分别有122（7%）和112（7%）名参与者失去随访。459例（28%）接受CDM的参与者与356例（21%）接受LCM的参与者发生新的WHO 4期事件或死亡（每100人年6.94例[95% CI 6.33 - 7.60] vs 5.24例[4.72 - 5.81]；绝对差异1.70例/ 100人年[0.87 - 2.54];HR 1.31例[1.14 - 1.51];p= 0.0001）。从ART治疗的第三年开始，疾病进展就出现了差异，而从第二年开始，LCM患者转向二线治疗的比例更高。CDM组283例（17%）和LCM组260例（16%）出现了新的严重不良事件（HR 1.12 [0.94 - 1.32]; p= 0.19），其中贫血最为常见（76例对61例）。抗逆转录病毒治疗可以在没有毒性作用的常规实验室监测的情况下安全进行，但疾病进展的差异表明，从抗逆转录病毒治疗的第二年开始监测cd4细胞计数，以指导转向二线治疗。英国医学研究委员会、英国国际发展部、洛克菲勒基金会、葛兰素史克、吉利德科学、勃林格殷格翰和雅培实验室。
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. 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 μL 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 μL (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. 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). 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. UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories.