title: Implementation and Operational Research: Risk Charts to Guide Targeted HIV-1 Viral Load Monitoring of ART: Development and Validation in Patients From Resource-Limited Settings.
abstract: BACKGROUND
  HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing.
  
  
  METHODS
  We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20%, or 40% of patients in 7 cohorts of patients starting ART in South Africa, and plotted cutoffs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia, and the Asia-Pacific.
  
  
  RESULTS
  In total, 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African cohort, from 64% to 93% in the Zambian cohort, and from 73% to 96% in the Asia-Pacific cohort. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia, and from 37% to 71% in Asia-Pacific. The area under the receiver operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia, and from 0.77 to 0.92 in Asia-Pacific.
  
  
  CONCLUSIONS
  CD4-based risk charts with optimal cutoffs for targeted VL testing maybe useful to monitor ART in settings where VL capacity is limited.
authors.affiliation: *Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; †Kheth'Impilo, Cape Town, South Africa; ‡Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; §Aurum Institute for Health Research, Johannesburg, South Africa; ‖Gugulethu ART Programme and Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa; ¶Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa; #Médecins Sans Frontières, Khayelitsha, Cape Town, South Africa; **Sinikithemba Clinic, McCord Hospital, Durban, South Africa; ††Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa; ‡‡Health Economics and Epidemiology Research Office, University of the Witwatersrand, Johannesburg, South Africa; §§Center for Global Health & Development and Department of Epidemiology, Boston University, Boston, MA; ‖‖Biostatistics and Databases Program, The Kirby Institute, Faculty of Medicine, The University of New South Wales, Sydney, Australia; and ¶¶Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, South Africa.
authors.forename: Manuel
authors.initials: M
authors.lastname: Koller
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Fatti
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Chi
authors.forename: Olivia
authors.initials: O
authors.lastname: Keiser
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hoffmann
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Hans
authors.initials: H
authors.lastname: Prozesky
authors.forename: Kathryn
authors.initials: K
authors.lastname: Stinson
authors.forename: Janet
authors.initials: J
authors.lastname: Giddy
authors.forename: Portia
authors.initials: P
authors.lastname: Mutevedzi
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Fox
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000191:economics* / Q000627:therapeutic use*; D001208:Asia / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015203:Reproducibility of Results; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult; D015024:Zambia / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents