BACKGROUND: Viral load (VL) quantification is considered essential for determining antiretroviral treatment (ART) success in resource-rich countries. However, it is not widely available in resource-limited settings where the burden of human immunodeficiency virus infection is greatest. In the absence of VL monitoring, switches to second-line ART are based on World Health Organization (WHO) clinical or immunologic failure criteria. METHODS: We assessed the performance of CD4 cell criteria to predict virologic outcomes in a large ART program in Nigeria. Laboratory monitoring consists of CD4 cell count and VL at baseline, then every 6 months. Failure was defined as 2 consecutive VLs >1000 copies/mL after at least 6 months of ART. Virologic outcomes were compared with the 3 WHO-defined immunologic failure criteria. RESULTS: A total of 9690 patients were included in the analysis (median follow-up, 33.2 months). A total of 1225 patients experienced failure by both immunologic and virologic criteria, 872 by virologic criteria only, and 1897 by immunologic criteria only. The sensitivity of CD4 cell criteria to detect viral failure was 58%, specificity was 75%, and the positive-predictive value was 39%. For patients with both virologic and immunologic failure, VL criteria identified failure significantly earlier than CD4 cell criteria (median, 10.4 vs 15.6 months; P < .0001). CONCLUSIONS: Because of the low sensitivity of immunologic criteria, a substantial number of failures are missed, potentially resulting in accumulation of resistance mutations. In addition, specificity and predictive values are low, which may result in large numbers of unnecessary ART switches. Monitoring solely by immunologic criteria may result in increased costs because of excess switches to more expensive ART and development of drug-resistant virus.
BACKGROUND: Viral load (VL) quantification is considered essential for determining antiretroviral treatment (ART) success in resource-rich countries. However, it is not widely available in resource-limited settings where the burden of human immunodeficiency virus infection is greatest. In the absence of VL monitoring, switches to second-line ART are based on World Health Organization (WHO) clinical or immunologic failure criteria. METHODS: We assessed the performance of CD4 cell criteria to predict virologic outcomes in a large ART program in Nigeria. Laboratory monitoring consists of CD4 cell count and VL at baseline, then every 6 months. Failure was defined as 2 consecutive VLs >1000 copies/mL after at least 6 months of ART. Virologic outcomes were compared with the 3 WHO-defined immunologic failure criteria. RESULTS: A total of 9690 patients were included in the analysis (median follow-up, 33.2 months). A total of 1225 patients experienced failure by both immunologic and virologic criteria, 872 by virologic criteria only, and 1897 by immunologic criteria only. The sensitivity of CD4 cell criteria to detect viral failure was 58%, specificity was 75%, and the positive-predictive value was 39%. For patients with both virologic and immunologic failure, VL criteria identified failure significantly earlier than CD4 cell criteria (median, 10.4 vs 15.6 months; P < .0001). CONCLUSIONS: Because of the low sensitivity of immunologic criteria, a substantial number of failures are missed, potentially resulting in accumulation of resistance mutations. In addition, specificity and predictive values are low, which may result in large numbers of unnecessary ART switches. Monitoring solely by immunologic criteria may result in increased costs because of excess switches to more expensive ART and development of drug-resistant virus.
Authors: Alexandra Calmy; Nathan Ford; Bernard Hirschel; Steven J Reynolds; Lut Lynen; Eric Goemaere; Felipe Garcia de la Vega; Luc Perrin; William Rodriguez Journal: Clin Infect Dis Date: 2006-11-28 Impact factor: 9.079
Authors: Melanie A Thompson; Judith A Aberg; Pedro Cahn; Julio S G Montaner; Giuliano Rizzardini; Amalio Telenti; José M Gatell; Huldrych F Günthard; Scott M Hammer; Martin S Hirsch; Donna M Jacobsen; Peter Reiss; Douglas D Richman; Paul A Volberding; Patrick Yeni; Robert T Schooley Journal: JAMA Date: 2010-07-21 Impact factor: 56.272
Authors: José Valdez Madruga; Pedro Cahn; Beatriz Grinsztejn; Richard Haubrich; Jacob Lalezari; Anthony Mills; Gilles Pialoux; Timothy Wilkin; Monika Peeters; Johan Vingerhoets; Goedele de Smedt; Lorant Leopold; Roberta Trefiglio; Brian Woodfall Journal: Lancet Date: 2007-07-07 Impact factor: 79.321
Authors: Alessandro Cozzi-Lepri; Andrew N Phillips; Lidia Ruiz; Bonaventura Clotet; Clive Loveday; Jesper Kjaer; Helene Mens; Nathan Clumeck; Ludmila Viksna; Francisco Antunes; Ladislav Machala; Jens D Lundgren Journal: AIDS Date: 2007-03-30 Impact factor: 4.177
Authors: S E Rutstein; C E Golin; S B Wheeler; D Kamwendo; M C Hosseinipour; M Weinberger; W C Miller; A K Biddle; A Soko; M Mkandawire; R Mwenda; A Sarr; S Gupta; R Mataya Journal: AIDS Care Date: 2015-08-17
Authors: Awachana Jiamsakul; Azar Kariminia; Keri N Althoff; Carina Cesar; Claudia P Cortes; Mary-Ann Davies; Viet Chau Do; Brian Eley; John Gill; Nagalingeswaran Kumarasamy; Daisy Maria Machado; Richard Moore; Hans Prozesky; Elizabeth Zaniewski; Matthew Law Journal: J Acquir Immune Defic Syndr Date: 2017-11-01 Impact factor: 3.731
Authors: Kristjana H Ásbjörnsdóttir; James P Hughes; Dalton Wamalwa; Agnes Langat; Jennifer A Slyker; Hellen M Okinyi; Julie Overbaugh; Sarah Benki-Nugent; Kenneth Tapia; Elizabeth Maleche-Obimbo; Ali Rowhani-Rahbar; Grace John-Stewart Journal: AIDS Date: 2016-11-28 Impact factor: 4.177
Authors: Zachary J Tabb; Blandina T Mmbaga; Monica Gandhi; Alexander Louie; Karen Kuncze; Hideaki Okochi; Aisa M Shayo; Elizabeth L Turner; Coleen K Cunningham; Dorothy E Dow Journal: AIDS Date: 2018-06-01 Impact factor: 4.177
Authors: Christopher J Hoffmann; Michael Schomaker; Matthew P Fox; Portia Mutevedzi; Janet Giddy; Hans Prozesky; Robin Wood; Daniela B Garone; Matthias Egger; Andrew Boulle Journal: J Acquir Immune Defic Syndr Date: 2013-05-01 Impact factor: 3.731