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.
-
picture_as_pdf - mmc1.pdf
-
subject - Published Version
-
- Available under Creative Commons: Attribution-NonCommercial-No Derivative Works 3.0