The use of pooled viral load testing to identify antiretroviral treatment failure.
BACKGROUND
To develop less costly methods to virologically monitor patients receiving antiretroviral therapy, we evaluated methods that use pooled blood samples and quantitative information available from viral load assays to monitor a cohort of patients on first-line antiretroviral therapy for virologic failure.


METHODS
We evaluated 150 blood samples collected after 6 months of therapy from participants enrolled in a San Diego primary infection program between January 1998 and January 2007. Samples were screened for virologic failure with individual viral load testing, 10 x 10 matrix pools and minipools of five samples. For the pooled platforms (matrix and minipools), we used a search and retest algorithm based on the quantitative viral load data to resolve samples that remained ambiguous for virologic failure. Viral load thresholds were more than 500 and more than 1500 copies/ml for the matrix and more than 250 and more than 500 copies/ml for the minipool. Efficiency, accuracy and result turnaround times were evaluated.


RESULTS
Twenty-three percent of cohort samples were detectable at more than 50 HIV RNA copies/ml. At an algorithm threshold of more than 500 HIV RNA copies/ml, both minipool and matrix methods used less than half the number of viral load assays to screen the cohort, compared with testing samples individually. Both pooling platforms had negative predictive values of 100% for viral loads of more than 500 HIV RNA copies/ml and at least 94% for viral loads of more than 250 HIV RNA copies/ml.


CONCLUSIONS
In this cohort, both pooling methods improved the efficiency of virologic monitoring over individual testing with a minimal decrease in accuracy. These methods may allow for the induction and sustainability of the virologic monitoring of patients receiving antiretroviral therapy in resource-limited settings.
Smith
Davey M
DM
University of California San Diego, La Jolla, CA 92093-0679, USA. davey@ucsd.edu
May
Susanne J
SJ
Pérez-Santiago
Josué
J
Strain
Matthew C
MC
Ignacio
Caroline C
CC
Haubrich
Richard H
RH
Richman
Douglas D
DD
Benson
Constance A
CA
Little
Susan J
SJ
D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000191:economics / Q000821:virology*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques / Q000191:economics / Q000379:methods; D012367:RNA, Viral / Q000097:blood*; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult
D044966:Anti-Retroviral Agents; D012367:RNA, Viral