Rates and Predictors of Failure of First-line Antiretroviral Therapy and Switch to Second-line ART in South Africa

Center for Global Health and Development, Boston University, 801 Massachusetts Ave., Boston, MA 02118, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 03/2012; 60(4):428-37. DOI: 10.1097/QAI.0b013e3182557785
Source: PubMed


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 confirmation 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 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).
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.

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    • "We have reported clinical outcomes for adults on ART in this programme that are broadly similar to other public sector programmes in South Africa [11-13]. However, the programme’s systems for detection and management of ART failure have been relatively ineffective, to the extent that, of the 20 000 adults enrolled on ART by the end of 2010, fewer than 100 (0.5%) had been switched to second-line ART regimens despite virological failure rates comparable to other programmes in the region [14]. The implementation of antiretroviral drug resistance testing as part of a research study provided an opportunity to address the backlog of treatment failure cases and provide focused training to staff on the detection and management of treatment failure, whilst simultaneously facilitating drug resistance surveillance and research. "
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