TitleRates and Predictors of Failure of First-line Antiretroviral Therapy and Switch to Second-line ART in South Africa
AuthorsMatthew P. Fox, Gilles Van Cutsem, Janet Giddy, Mhairi Maskew, Olivia Keiser, Hans Prozesky, Robin Wood, Miguel A. Hernán, Jonathan A. C. Sterne, Matthias Egger, & Andrew Boulle
PublicationJournal of Acquired Immune Deficiency Syndromes. 2012 Aug; 60(4):428-437.


To measure rates and predictors of virologic failure and switch to second-line antiretroviral therapy (ART) in South Africa.


Observational cohort study.


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 confirma- tion above varying thresholds) and switching to second-line ART.


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 confirma- tory 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).


In resource-limited settings with viral load monitoring, virologic failure rates are highly sensitive to thresholds for confirma- tion. Despite clear guidelines there is considerable variability in switching failing patients, partially in response t
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