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

Abstract

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.

DOI: 10.1016/S0140-6736(09)62067-5

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@article{Mugyenyi2010RoutineVC, title={Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial}, author={P Mugyenyi and A S Walker and J Hakim and P Munderi and D M Gibb and C Kityo and A Reid and H Grosskurth and J H Darbyshire and F Ssali and D Bray and E Katabira and A G Babiker and C F Gilks and G Kabuye and D Nsibambi and R Kasirye and E Zalwango and M Nakazibwe and B Kikaire and G Nassuna and R Massa and K Fadhiru and M Namyalo and A Zalwango and L Generous and P Khauka and N Rutikarayo and W Nakahima and A Mugisha and J Todd and J Levin and S Muyingo and A Ruberantwari and P Kaleebu and D Yirrell and N Ndembi and F Lyagoba and P Hughes and M Aber and A Medina Lara and S Foster and J Amurwon and B Nyanzi Wakholi and J Whitworth and K Wangati and B Amuron and D Kajungu and J Nakiyingi and W Omony and D Tumukunde and T Otim and J Kabanda and H Musana and J Akao and H Kyomugisha and A Byamukama and J Sabiiti and J Komugyena and P Wavamunno and S Mukiibi and A Drasiku and R Byaruhanga and O Labeja and P Katundu and S Tugume and P Awio and A Namazzi and G T Bakeinyaga and H Katabira and D Abaine and J Tukamushaba and W Anywar and W Ojiambo and E Angweng and S Murungi and W Haguma and S Atwiine and J Kigozi and L Namale and A Mukose and G Mulindwa and D Atwiine and A Muhwezi and E Nimwesiga and G Barungi and J Takubwa and D Mwebesa and G Kagina and M Mulindwa and F Ahimbisibwe and P Mwesigwa and S Akuma and C Zawedde and D Nyiraguhirwa and C Tumusiime and L Bagaya and W Namara and J Karungi and R Kankunda and R Enzama and A Latif and V Robertson and E Chidziva and R Bulaya-Tembo and G Musoro and F Taziwa and C Chimbetete and L Chakonza and A Mawora and C Muvirimi and G Tinago and P Svovanapasis and M Simango and O Chirema and J Machingura and S Mutsai and M Phiri and T Bafana and M Chirara and L Muchabaiwa and M Muzambi and J Mutowo and T Chivhunga and E Chigwedere and M Pascoe and C Warambwa and E Zengeza and F Mapinge and S Makota and A Jamu and N Ngorima and H Chirairo and S Chitsungo and J Chimanzi and C Maweni and R Warara and M Matongo and S Mudzingwa and M Jangano and K Moyo and L Vere and N Mdege and I Machingura and A Ronald and A Kambungu and F Lutwama and I Mambule and A Nanfuka and J Walusimbi and E Nabankema and R Nalumenya and T Namuli and R Kulume and I Namata and L Nyachwo and A Florence and A Kusiima and E Lubwama and R Nairuba and F Oketta and E Buluma and R Waita and H Ojiambo and F Sadik and J Wanyama and P Nabongo and J Oyugi and F Sematala and A Muganzi and C Twijukye and H Byakwaga and R Ochai and D Muhweezi and A Coutinho and B Etukoit and C Gilks and K Boocock and C Puddephatt and C Grundy and J Bohannon and D Winogron and A Burke and A Babiker and H Wilkes and M Rauchenberger and S Sheehan and C Spencer-Drake and K Taylor and M Spyer and A Ferrier and B Naidoo and D Dunn and R Goodall and L Peto and R Nanfuka and C Mufuka-Kapuya and D Pillay and A McCormick and I Weller and S Bahendeka and M Bassett and A Chogo Wapakhabulo and B Gazzard and C Mapuchere and O Mugurungi and C Burke and S Jones and C Newland and G Pearce and S Rahim and J Rooney and M Smith and W Snowden and J-M Steens and A Breckenridge and A McLaren and C Hill and J Matenga and A Pozniak and D Serwadda and T Peto and A Palfreeman and M Borok}, journal={The Lancet}, year={2010}, volume={375}, pages={123-131} }