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
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.
|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)|
|Sensitivity||51.7%||55.0%|| ||11.0%|| ||26.6%||4.5%||6.3%|
|Specificity||93.9%||82.9%|| ||90.5%|| ||86.0%||99.3%||97.7%|
|NPV||98.6%||90.5%|| ||91.1%|| ||91.1%||85.5%||91.8%|
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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