OBJECTIVES: Without resistance tests, deciding which patients with virological failure should switch to second-line antiretroviral therapy (ART) is difficult. The factors influencing this decision are poorly understood. We assess predictors of switching regimens after virological failure. DESIGN: Retrospective cohort study using clinical data from a South African ART program with 6-monthly viral load (VL) monitoring. METHODS: We constructed a dataset of patient visits occurring following first-line virological failure, and used random effects logistic regression (accounting for individual-level and clinic-level clustering) to assess predictors of switching at each visit. RESULTS: One thousand six hundred sixty-eight patients with virological failure (73% male, mean age 41 years, median CD4 184 cells/mm, mean log10 VL 4.3) contributed 1922 person-years of viremia. 12 months after failure, the cumulative incidence of switching regimen, viral resuppression, or death was 16.9%, 13.2%, and 4.6%, respectively. In adjusted analysis, switching was more likely at the third or subsequent visit after failure; in visits occurring in 2008 versus 2003 to 2007; and in patients with ART experience pre-programme, current high VL or low CD4 count. Switching was less likely in patients with no clinic contact for 4 months, or declining VL. Switching rates varied between clinics with clinic-level clustering evident in the final model (P <0.001). CONCLUSIONS: Despite 6-monthly virological monitoring and recommendations to switch after adherence interventions and confirmed viremia, patients experienced delayed switching. Individual-level covariates influenced switching but did not account for variable switching rates between clinics, suggesting differences in guideline implementation. In certain circumstances delays may be warranted; however understanding barriers to guideline implementation will limit unnecessary delays.
OBJECTIVES: Without resistance tests, deciding which patients with virological failure should switch to second-line antiretroviral therapy (ART) is difficult. The factors influencing this decision are poorly understood. We assess predictors of switching regimens after virological failure. DESIGN: Retrospective cohort study using clinical data from a South African ART program with 6-monthly viral load (VL) monitoring. METHODS: We constructed a dataset of patient visits occurring following first-line virological failure, and used random effects logistic regression (accounting for individual-level and clinic-level clustering) to assess predictors of switching at each visit. RESULTS: One thousand six hundred sixty-eight patients with virological failure (73% male, mean age 41 years, median CD4 184 cells/mm, mean log10 VL 4.3) contributed 1922 person-years of viremia. 12 months after failure, the cumulative incidence of switching regimen, viral resuppression, or death was 16.9%, 13.2%, and 4.6%, respectively. In adjusted analysis, switching was more likely at the third or subsequent visit after failure; in visits occurring in 2008 versus 2003 to 2007; and in patients with ART experience pre-programme, current high VL or low CD4 count. Switching was less likely in patients with no clinic contact for 4 months, or declining VL. Switching rates varied between clinics with clinic-level clustering evident in the final model (P <0.001). CONCLUSIONS: Despite 6-monthly virological monitoring and recommendations to switch after adherence interventions and confirmed viremia, patients experienced delayed switching. Individual-level covariates influenced switching but did not account for variable switching rates between clinics, suggesting differences in guideline implementation. In certain circumstances delays may be warranted; however understanding barriers to guideline implementation will limit unnecessary delays.
Authors: Andrew N Phillips; Deenan Pillay; Alec H Miners; Diane E Bennett; Charles F Gilks; Jens D Lundgren Journal: Lancet Date: 2008-04-26 Impact factor: 79.321
Authors: Preeyaporn Srasuebkul; Poh Lian Lim; Man Po Lee; Nagalingeswaran Kumarasamy; Jialun Zhou; Thira Sirisanthana; Patrick C K Li; Adeeba Kamarulzaman; Shinichi Oka; Praphan Phanuphak; Saphonn Vonthanak; Tuti P Merati; Yi-Ming A Chen; Somnuek Sungkanuparph; Goa Tau; Fujie Zhang; Christopher K C Lee; Rossana Ditangco; Sanjay Pujari; Jun Y Choi; Jeffery Smith; Matthew G Law Journal: Clin Infect Dis Date: 2009-04-01 Impact factor: 9.079
Authors: Catherine Orrell; Guy Harling; Stephen D Lawn; Richard Kaplan; Matthew McNally; Linda-Gail Bekker; Robin Wood Journal: Antivir Ther Date: 2007
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
Authors: Preeyaporn Srasuebkul; Alexandra Calmy; Jialun Zhou; Nagalingeswaran Kumarasamy; Matthew Law; Poh Lian Lim Journal: AIDS Res Ther Date: 2007-09-17 Impact factor: 2.250
Authors: Andrew Phillips; Amir Shroufi; Lara Vojnov; Jennifer Cohn; Teri Roberts; Tom Ellman; Kimberly Bonner; Christine Rousseau; Geoff Garnett; Valentina Cambiano; Fumiyo Nakagawa; Deborah Ford; Loveleen Bansi-Matharu; Alec Miners; Jens D Lundgren; Jeffrey W Eaton; Rosalind Parkes-Ratanshi; Zachary Katz; David Maman; Nathan Ford; Marco Vitoria; Meg Doherty; David Dowdy; Brooke Nichols; Maurine Murtagh; Meghan Wareham; Kara M Palamountain; Christine Chakanyuka Musanhu; Wendy Stevens; David Katzenstein; Andrea Ciaranello; Ruanne Barnabas; R Scott Braithwaite; Eran Bendavid; Kusum J Nathoo; David van de Vijver; David P Wilson; Charles Holmes; Anna Bershteyn; Simon Walker; Elliot Raizes; Ilesh Jani; Lisa J Nelson; Rosanna Peeling; Fern Terris-Prestholt; Joseph Murungu; Tsitsi Mutasa-Apollo; Timothy B Hallett; Paul Revill Journal: Nature Date: 2015-12-03 Impact factor: 49.962
Authors: Maya L Petersen; Linh Tran; Elvin H Geng; Steven J Reynolds; Andrew Kambugu; Robin Wood; David R Bangsberg; Constantin T Yiannoutsos; Steven G Deeks; Jeffrey N Martin Journal: AIDS Date: 2014-09-10 Impact factor: 4.177
Authors: Lee Fairlie; Brad Karalius; Kunjal Patel; Russell B van Dyke; Rohan Hazra; Miguel A Hernán; George K Siberry; George R Seage; Allison Agwu; Andrew Wiznia Journal: AIDS Date: 2015-10-23 Impact factor: 4.177