145. High Rates of Treatment Failure Misclassification using 2010 vs. 2006 WHO Guidelines among HIV-infected Children in Siem Reap, Cambodia
Session: Oral Abstract Session: HIV Primary Care and Antiretroviral Therapy, Epidemiology and Testing
Friday, October 21, 2011: 9:00 AM
Room: 157ABC

Background: Antiretroviral therapy (ART) in resource-limited settings is typically monitored clinically and immunologically, according to World Health Organization (WHO) or national guidelines (GL). High misclassification rates (MR) of virologic failure by the 2006 WHO GL have been reported in adults and, recently, in children. Revised pediatric WHO GL were published in 2010, but their MR are unknown.

Methods: We evaluated MR of WHO-2006, WHO-2010, and Cambodia-2010 GL (30% CD4 decrease added to WHO-2010 criteria) based on GL-specified immunologic criteria. Children <15 years who received ≥6 months of 1st line ART at Angkor Hospital for Children, Siem Reap, Cambodia, between January 2005 and September 2010 were included. Routine viral load (VL) testing was done yearly, CD4 6-monthly and WHO staging bimonthly. We determined sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for each GL and compared MR using bootstrap resampling to account for multiple tests per child. Analysis was performed with R software.

Results: 457 children with 1079 VLs were included. Median age at diagnosis: 4.9 years (range <1 month to 13 years), median nadir %CD4: 11 (IQR: 517%). At the most recent VL, 92 (20%) had >400 copies/mL. For children with WHO stage 1/2, misclassification as failure (met CD4 failure criteria, but had undetectable VL) was 63% for WHO-2006, 33% for WHO-2010 and 81% for Cambodia-2010; misclassification as success (did not meet CD4 failure, but had detectable VL) was 10%, 12% and 12%. For children with WHO stage 3/4, misclassification as failure was 33%, 40% and 43%; misclassification as success was 14%, 24% and 20%. Compared to WHO-2006, WHO-2010 significantly increased the risk of misclassification as success in stage 3/4 (p<0.05). Cambodia-2010 greatly decreased specificity in stage 1/2 (83.7% vs. 99.8%, p<0.05), misclassifying 81% with immunologic failure.

Conclusion: In our cohort, lack of virologic monitoring would result in unacceptably high rates of treatment failure misclassification, leading to premature ART switch and resistance accumulation. Affordable routine virologic monitoring in resource-limited settings is desperately needed.


Subject Category: H. HIV/AIDS and other retroviruses

Benjamin P. Westley, MD1, Allison DeLong, MS2, Tray Chhraing, MD3, Sophearin Dim3, Elizabeth M. Dufort, MD4, Joseph I. Harwell, MD5 and Rami Kantor, MD6, (1)Division of Infectious Diseases, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, (2)Brown University, Statistical Sciences, Providence, RI, (3)Angkor Hospital for Children, Siem Reap, Cambodia, (4)Albany Medical College/Albany Medical Center, Albany, NY, (5)Alpert Medical School of Brown University, Hasbro Children's Hospital, Providence, RI, (6)Alpert Medical School of Brown University, The Miriam Hospital, Providence, RI

Disclosures:

B. P. Westley, None

A. DeLong, None

T. Chhraing, None

S. Dim, None

E. M. Dufort, None

J. I. Harwell, None

R. Kantor, None

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