edoc

Should viral load thresholds be lowered? Revisiting the WHO definition for virologic failure in patients on antiretroviral therapy in resource-limited settings

Labhardt, Niklaus D. and Bader, Joëlle and Lejone, Thabo Ishmael and Ringera, Isaac and Hobbins, Michael A. and Fritz, Christiane and Ehmer, Jochen and Cerutti, Bernard and Puga, Daniel and Klimkait, Thomas. (2016) Should viral load thresholds be lowered? Revisiting the WHO definition for virologic failure in patients on antiretroviral therapy in resource-limited settings. Medicine, 95 (28). e3985.

[img]
Preview
PDF - Published Version
Available under License CC BY-NC-ND (Attribution-NonCommercial-NoDerivatives).

341Kb

Official URL: http://edoc.unibas.ch/43745/

Downloads: Statistics Overview

Abstract

The World Health Organization (WHO) guidelines on antiretroviral therapy (ART) define treatment failure as 2 consecutive viral loads (VLs) ≥1000 copies/mL. There is, however, little evidence supporting 1000 copies as an optimal threshold to define treatment failure. Objective of this study was to assess the correlation of the WHO definition with the presence of drug-resistance mutations in patients who present with 2 consecutive unsuppressed VL in a resource-limited setting.In 10 nurse-led clinics in rural Lesotho children and adults on first-line ART for ≥6 months received a first routine VL. Those with plasma VL ≥80 copies/mL were enrolled in a prospective study, receiving enhanced adherence counseling (EAC) and a follow-up VL after 3 months. After a second unsuppressed VL genotypic resistance testing was performed. Viruses with major mutations against ≥2 drugs of the current regimen were classified as "resistant".A total of 1563 adults and 191 children received a first routine VL. Of the 138 adults and 53 children with unsuppressed VL (≥80 copies/mL), 165 (116 adults; 49 children) had a follow-up VL after EAC; 108 (74 adults; 34 children) remained unsuppressed and resistance testing was successful. Ninety of them fulfilled the WHO definition of treatment failure (both VL ≥1000 copies/mL); for another 18 both VL were unsuppressed but with <1000 copies/mL. The positive predictive value (PPV) for the WHO failure definition was 81.1% (73/90) for the presence of resistant virus. Among the 18 with VL levels between 80 and 1000 copies/mL, thereby classified as "non-failures", 17 (94.4%) harbored resistant viruses. Lowering the VL threshold from 1000 copies/mL to 80 copies/mL at both determinations had no negative influence on the PPV (83.3%; 90/108).The current WHO-definition misclassifies patients who harbor resistant virus at VL below 1000 c/mL as "nonfailing." Lowering the threshold to VL ≥80 copies/mL identifies a significantly higher number of patients with treatment-resistant virus and should be considered.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Labhardt, Niklaus
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Lippincott Williams & Wilkins
ISSN:1536-5964
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:26 Sep 2018 12:55
Deposited On:29 Aug 2016 13:44

Repository Staff Only: item control page