title: Pooled Nucleic Acid Testing to Detect Antiretroviral Treatment Failure in HIV-Infected Patients in Mozambique.
abstract: BACKGROUND
  In resource-limited settings, viral load monitoring of HIV-infected patients receiving antiretroviral therapy (ART) is not readily available because of high costs. Here, we compared the accuracy and costs of quantitative and qualitative pooled methods with standard viral load testing.
  
  
  METHODS
  Blood was collected prospectively from 461 patients receiving first-line ART in Mozambique who had not been evaluated previously with viral load testing. Screening for virologic failure of ART was performed quantitatively (ie, standard viral loads) and qualitatively [one and 2 rounds of polymerase chain reaction (PCR)]. Individual samples and minipools of 5 samples were then analyzed using both methods. The relative efficiency, accuracy, and costs of each method were calculated based on viral load thresholds for ART failure.
  
  
  RESULTS
  Standard viral load testing of individual samples revealed a high rate of ART failure (19%-23%) across all virologic failure thresholds, and the majority of the patients (93%) with viral loads >1500 copies per milliliter had genotypic resistance to drugs in their ART regimen. Pooled quantitative screening and deconvolution testing had positive and negative predictive values exceeding 95% with cost savings of $11,250 compared with quantitative testing of each sample individually. Pooled qualitative screening and deconvolution testing had a higher cost savings of $30,147 for 1 PCR round and $25,535 for 2 PCR rounds compared with quantitative testing each sample individually. Both pooled qualitative PCR methods had positive and negative predictive values ≥90%, but the pooled 1-round PCR method had a sensitivity of 64%.
  
  
  CONCLUSIONS
  Given the high rate of undiagnosed ART failure and drug resistance in this cohort, it is clear that virologic monitoring is urgently needed in this population. Here, we compared alternative methods of virologic monitoring with standard viral load testing of individual samples and found these methods to be cost saving and accurate. The test characteristics of each method will likely need to be considered for each local population before it is adopted.
authors.affiliation: *HIV, STD and Hepatitis Branch of Public Health Services, Health and Human Services, County of San Diego, San Diego, CA; †University of California, San Diego, La Jolla, CA; ‡Department of Microbiology, Universidade Eduardo Mondlane, Maputo, Mozambique; §Department of Biostatistics, University of Washington, Seattle, WA; and ‖Veterans Affairs San Diego Healthcare System, San Diego, CA.
authors.forename: Myres
authors.initials: M
authors.lastname: Tilghman
authors.forename: Daniel
authors.initials: D
authors.lastname: Tsai
authors.forename: Titos P
authors.initials: TP
authors.lastname: Buene
authors.forename: Manuel
authors.initials: M
authors.lastname: Tomas
authors.forename: Salma
authors.initials: S
authors.lastname: Amade
authors.forename: Daniel
authors.initials: D
authors.lastname: Gehlbach
authors.forename: Stephanie
authors.initials: S
authors.lastname: Chang
authors.forename: Caroline
authors.initials: C
authors.lastname: Ignacio
authors.forename: Gemma
authors.initials: G
authors.lastname: Caballero
authors.forename: Stephen
authors.initials: S
authors.lastname: Espitia
authors.forename: Susanne
authors.initials: S
authors.lastname: May
authors.forename: Emilia V
authors.initials: EV
authors.lastname: Noormahomed
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D006801:Humans; D009073:Mozambique / Q000453:epidemiology; D016133:Polymerase Chain Reaction / Q000379:methods*; D012367:RNA, Viral / Q000302:isolation & purification*; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral