OBJECTIVES: To measure rates and predictors of virologic failure and switch to second-line antiretroviral therapy (ART) in South Africa. DESIGN: : Observational cohort study. METHODS: We included ART-naive adult patients initiated on public sector ART (January 2000 to July 2008) at 5 sites in South Africa who completed ≥6 months of follow-up. We estimated cumulative risk of virologic failure (viral load ≥400 copies/mL with confirmation above varying thresholds) and switching to second-line ART. RESULTS: Nineteen thousand six hundred forty-five patients (29,935 person-years) had a median of 1.3 years of study follow-up (1.8 years on ART) and a median CD4 count of 93 (IQR: 39-155) cells per microliter at ART initiation. About 9.9% (4.5 per 100 person-years) failed ART in median 16 (IQR: 12-23) months since ART initiation, with median 2.7 months (IQR: 1.6-4.7) months between first elevated and confirmatory viral loads. By survival analysis, using a confirmatory threshold of 400 copies per milliliter, 16.9% [95% confidence interval (CI): 15.4% to 18.6%] failed by 5 years on ART, but only 7.8% (95% CI: 6.6% to 9.3%) using a threshold of 10,000. CD4 <25 versus 100-199 (adjusted HR: 1.60; 95% CI: 1.37 to 1.87), ART initiation viral load ≥1,000,000 versus <10,000, (1.32; 0.91 to 1.93), and 2+ gaps in care versus 0 (95% CI: 7.25; 4.95 to 10.6) were predictive of failure. Overall, 10.1% (95% CI: 9.0% to 11.4%) switched to second-line by 5 years on ART. Lower CD4 at failure and higher rate of CD4 decline were predictive of switch (decline 100% to 51% versus 25% to -25%, adjusted HR: 1.96; 95% CI: 1.35 to 2.85). CONCLUSIONS: In resource-limited settings with viral load monitoring, virologic failure rates are highly sensitive to thresholds for confirmation. Despite clear guidelines there is considerable variability in switching failing patients, partially in response to immunologic status and postfailure evolution.
OBJECTIVES: To measure rates and predictors of virologic failure and switch to second-line antiretroviral therapy (ART) in South Africa. DESIGN: : Observational cohort study. METHODS: We included ART-naive adult patients initiated on public sector ART (January 2000 to July 2008) at 5 sites in South Africa who completed ≥6 months of follow-up. We estimated cumulative risk of virologic failure (viral load ≥400 copies/mL with confirmation above varying thresholds) and switching to second-line ART. RESULTS: Nineteen thousand six hundred forty-five patients (29,935 person-years) had a median of 1.3 years of study follow-up (1.8 years on ART) and a median CD4 count of 93 (IQR: 39-155) cells per microliter at ART initiation. About 9.9% (4.5 per 100 person-years) failed ART in median 16 (IQR: 12-23) months since ART initiation, with median 2.7 months (IQR: 1.6-4.7) months between first elevated and confirmatory viral loads. By survival analysis, using a confirmatory threshold of 400 copies per milliliter, 16.9% [95% confidence interval (CI): 15.4% to 18.6%] failed by 5 years on ART, but only 7.8% (95% CI: 6.6% to 9.3%) using a threshold of 10,000. CD4 <25 versus 100-199 (adjusted HR: 1.60; 95% CI: 1.37 to 1.87), ART initiation viral load ≥1,000,000 versus <10,000, (1.32; 0.91 to 1.93), and 2+ gaps in care versus 0 (95% CI: 7.25; 4.95 to 10.6) were predictive of failure. Overall, 10.1% (95% CI: 9.0% to 11.4%) switched to second-line by 5 years on ART. Lower CD4 at failure and higher rate of CD4 decline were predictive of switch (decline 100% to 51% versus 25% to -25%, adjusted HR: 1.96; 95% CI: 1.35 to 2.85). CONCLUSIONS: In resource-limited settings with viral load monitoring, virologic failure rates are highly sensitive to thresholds for confirmation. Despite clear guidelines there is considerable variability in switching failing patients, partially in response to immunologic status and postfailure evolution.
Authors: Anthony D Harries; Rony Zachariah; Joep J van Oosterhout; Steven D Reid; Mina C Hosseinipour; Vic Arendt; Zengani Chirwa; Andreas Jahn; Erik J Schouten; Kelita Kamoto Journal: Lancet Infect Dis Date: 2010-01 Impact factor: 25.071
Authors: Olivia Keiser; Benjamin H Chi; Thomas Gsponer; Andrew Boulle; Catherine Orrell; Sam Phiri; Nicola Maxwell; Mhairi Maskew; Hans Prozesky; Matthew P Fox; Andrew Westfall; Matthias Egger Journal: AIDS Date: 2011-09-10 Impact factor: 4.177
Authors: Jean B Nachega; Michael Hislop; David W Dowdy; Richard E Chaisson; Leon Regensberg; Gary Maartens Journal: Ann Intern Med Date: 2007-04-17 Impact factor: 25.391
Authors: David M Moore; Anna Awor; Robert Downing; Jonathan Kaplan; Julio S G Montaner; John Hancock; Willy Were; Jonathan Mermin Journal: J Acquir Immune Defic Syndr Date: 2008-12-15 Impact factor: 3.731
Authors: Olivia Keiser; Patrick MacPhail; Andrew Boulle; Robin Wood; Mauro Schechter; François Dabis; Eduardo Sprinz; Matthias Egger Journal: Trop Med Int Health Date: 2009-07-14 Impact factor: 2.622
Authors: Morna Cornell; Karl Technau; Lara Fairall; Robin Wood; Harry Moultrie; Gilles van Cutsem; Janet Giddy; Lerato Mohapi; Brian Eley; Patrick MacPhail; Hans Prozesky; Helena Rabie; Mary-Ann Davies; Nicola Maxwell; Andrew Boulle Journal: S Afr Med J Date: 2009-09
Authors: Ian M Sanne; Daniel Westreich; Andrew P Macphail; Dennis Rubel; Pappie Majuba; Annelies Van Rie Journal: J Int AIDS Soc Date: 2009-12-17 Impact factor: 5.396
Authors: Alyssa F Harlow; Jacob Bor; Alana T Brennan; Mhairi Maskew; William MacLeod; Sergio Carmona; Koleka Mlisana; Matthew P Fox Journal: Am J Epidemiol Date: 2020-12-01 Impact factor: 4.897
Authors: Isaac Singini; Thomas B Campbell; Laura M Smeaton; Nagalingeswaran Kumarasamy; Alberto La Rosa; Sineenart Taejareonkul; Steven A Safren; Timothy P Flanigan; James G Hakim; Michael D Hughes Journal: HIV Clin Trials Date: 2016-07-29
Authors: Vincent C Marconi; Baohua Wu; Jane Hampton; Claudia E Ordóñez; Brent A Johnson; Dinesh Singh; Sally John; Michelle Gordon; Anna Hare; Richard Murphy; Jean Nachega; Daniel R Kuritzkes; Carlos del Rio; Henry Sunpath Journal: AIDS Patient Care STDS Date: 2013-12 Impact factor: 5.078
Authors: Allison Navis; Ifunanya Dallah; Charles Mabeta; Kalo Musukuma; Omar K Siddiqi; Christopher M Bositis; Igor J Koralnik; Harris A Gelbard; William H Theodore; Jason F Okulicz; Brent A Johnson; Izukanji Sikazwe; David R Bearden; Gretchen L Birbeck Journal: Epilepsia Date: 2020-10-21 Impact factor: 5.864
Authors: Anna Q Hare; Claudia E Ordóñez; Brent A Johnson; Carlos Del Rio; Rachel A Kearns; Baohua Wu; Jane Hampton; Peng Wu; Henry Sunpath; Vincent C Marconi Journal: AIDS Behav Date: 2014-11
Authors: Christopher J Hoffmann; Silvia Cohn; Fildah Mashabela; Jennifer D Hoffmann; Helen McIlleron; Paolo Denti; David W Haas; Kelly E Dooley; Neil A Martinson; Richard E Chaisson Journal: J Acquir Immune Defic Syndr Date: 2016-01-01 Impact factor: 3.731