7th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013)


TUPE269 - Poster Exhibition

Predicting treatment failure (TF) in adults and children on antiretroviral therapy (ART): systematic review of the performance characteristics of the 2010 World Health Organization (WHO) criteria for virologic failure

G.W. Rutherford1, A.T. Anglemyer1, P. Easterbrook2, T. Horvath1, M. Vitoria2, M. Penazzato2, M. Doherty2

1University of California, San Francisco, Cochrane HIV/AIDS Group, Global Health Sciences, San Francisco, United States, 2World Health Organization, Department of HIV/AIDS, Geneva, Switzerland

Background: Most ART programs in resource-limited settings do not have access to viral load (VL) testing and use clinical and immunologic monitoring to assess response to ART and determine TF. WHO has developed simplified immunologic and clinical criteria to diagnose TF and guide switches to second-line therapy. We conducted a systematic review to assess how accurately these criteria predicted TF in studies that used different VL thresholds in adults and children.
Methods: 2010 WHO criteria for TF were: new or recurrent stage 4 condition (excluding immune reconstitution syndrome) (clinical criteria); OR a fall of CD4 count to baseline or below OR a 50% fall from on-treatment peak value OR persistent levels < 100 cells/µL (< 200 cells/µL or CD4 < 10% in 2-5 year olds) (immunologic criteria). We searched for studies that evaluated performance of the 2010 criteria for predicting VL of ≥50 and ≥5000 (current suggested threshold) copies/mL. We calculated pooled sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the immunologic and clinical criteria, alone and in combination, for predicting TF.
Results: From 428 studies, we identified 17 eligible studies (13 adult and 4 pediatric) from Africa, Asia and South America.
Performance characteristics of 2010 WHO criteria for treatment failure by VL threshold.

 ImmunologicClinicalImmunologic OR clinicalImmunologic
VL threshold (copies/ml)≥5000≥50≥5000≥50≥5000≥50≥5000≥400
N (studies)2288 (3)15581 (12)1 (1)919 (3)92 (1)1583 (6)4100 (3)2256 (1)
Sensitivity51.7%55.0% 11.0% 26.6%4.5%6.3%
Specificity93.9%82.9% 90.5% 86.0%99.3%97.7%
NPV98.6%90.5% 91.1% 91.1%85.5%91.8%
[Performance characteristics]

Conclusion: The 2010 immunologic and clinical criteria for TF have low sensitivity and PPV for identifying those with VL failure, especially children. Use of a lower VL threshold had minimal impact on performance of the WHO criteria. These findings highlight the importance of confirming TF to avoid unnecessary switching to second-line ART and the need to improve criteria, especially for children.

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