Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.
;
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;
GT 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;
DM Gibb;
A Burke;
D Bray;
A Babiker;
AS Walker;
H Wilkes;
M Rauchenberger;
S Sheehan;
C Spencer-Drake;
K Taylor;
M Spyer;
A Ferrier;
B Naidoo;
D Dunn;
R Goodall;
JH 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;
JH 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;
(2010)
Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.
Lancet, 375 (9709).
pp. 123-131.
ISSN 0140-6736
DOI: 10.1016/S0140-6736(09)62067-5
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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