BACKGROUND:Structured treatment interruption (STI) of antiretroviral therapy (ART) could potentially reduce cost and toxicity, but clinical efficacy requires evaluation. METHODS: An assessment of fixed-duration STI was nested in DART, a multicentre trial comparing strategies for monitoring ART in Uganda and Zimbabwe (ISCRTN 13968779). Of 3316 ART-naive symptomatic adults with CD4 cell count <; 200 cells/microl at ART initiation, 813 with > or = 300 cells/microl after 48 or 72 weeks underwent a second randomization to either STI, cycles of 12 weeks on/off (408), or continuous ART (CT; 405). RESULTS: Median age at STI/CT randomization was 37 years (range, 19-67) and CD4 cell count 358 cells/microl (range, 300-1054). A second review terminated the STI/CT randomisation on 15 March 2006, and participants changed to CT. Median follow-up was 51 weeks (range, 0-85): 99% and 50% of time was spent on ART in CT and STI, respectively. First new World Health Organization (WHO) stage 4 events or death occurred more frequently in STI (24; 6.4/100 person-years) than CT (9; 2.4/100 person-years) (hazard ratio, 2.73; 95% confidence interval, 1.27-5.88; P = 0.007); oesophageal candidiasis being the most frequent event (STI, 13; CT, 3). Nine (1%) participants died (STI, 5; CT, 4). There was no difference in time to first serious adverse event (P = 0.78), although ART change owing to toxicity occurred more with CT (10; 2.6/100 person-years) than with STI (2; 0.5/100 person-years) (P = 0.02). CONCLUSIONS: Although absolute rates of WHO stage 4 events/death were low, 12 week STIS initiated at a CD4 cell count >/= 300 cells/microl resulted in a greater than twofold increased relative rate of disease progression compared with continuous therapy in adult Africans initiating ART with advanced disease, and cannot be recommended.
RCT Entities:
BACKGROUND: Structured treatment interruption (STI) of antiretroviral therapy (ART) could potentially reduce cost and toxicity, but clinical efficacy requires evaluation. METHODS: An assessment of fixed-duration STI was nested in DART, a multicentre trial comparing strategies for monitoring ART in Uganda and Zimbabwe (ISCRTN 13968779). Of 3316 ART-naive symptomatic adults with CD4 cell count < 200 cells/microl at ART initiation, 813 with > or = 300 cells/microl after 48 or 72 weeks underwent a second randomization to either STI, cycles of 12 weeks on/off (408), or continuous ART (CT; 405). RESULTS: Median age at STI/CT randomization was 37 years (range, 19-67) and CD4 cell count 358 cells/microl (range, 300-1054). A second review terminated the STI/CT randomisation on 15 March 2006, and participants changed to CT. Median follow-up was 51 weeks (range, 0-85): 99% and 50% of time was spent on ART in CT and STI, respectively. First new World Health Organization (WHO) stage 4 events or death occurred more frequently in STI (24; 6.4/100 person-years) than CT (9; 2.4/100 person-years) (hazard ratio, 2.73; 95% confidence interval, 1.27-5.88; P = 0.007); oesophageal candidiasis being the most frequent event (STI, 13; CT, 3). Nine (1%) participants died (STI, 5; CT, 4). There was no difference in time to first serious adverse event (P = 0.78), although ART change owing to toxicity occurred more with CT (10; 2.6/100 person-years) than with STI (2; 0.5/100 person-years) (P = 0.02). CONCLUSIONS: Although absolute rates of WHO stage 4 events/death were low, 12 week STIS initiated at a CD4 cell count >/= 300 cells/microl resulted in a greater than twofold increased relative rate of disease progression compared with continuous therapy in adult Africans initiating ART with advanced disease, and cannot be recommended.
Authors: Lee D Pyne-Mercier; Grace C John-Stewart; Barbra A Richardson; Njeri L Kagondu; Joan Thiga; Haidy Noshy; Nadia Kist; Michael H Chung Journal: AIDS Care Date: 2011-05
Authors: A S Walker; D Ford; C F Gilks; P Munderi; F Ssali; A Reid; E Katabira; H Grosskurth; P Mugyenyi; J Hakim; J H Darbyshire; D M Gibb; A G Babiker Journal: Lancet Date: 2010-03-27 Impact factor: 79.321
Authors: Risa M Hoffman; Erin Leister; Deborah Kacanek; David E Shapiro; Jennifer S Read; Yvonne Bryson; Judith S Currier Journal: J Acquir Immune Defic Syndr Date: 2013-08-15 Impact factor: 3.731
Authors: 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 Journal: Lancet Date: 2009-12-08 Impact factor: 79.321