Date Published: July 13, 2017
Publisher: Public Library of Science
Author(s): Joy Chang, Amina de Sousa, Jennifer Sabatier, Mariamo Assane, Guoqing Zhang, Dulce Bila, Paula Vaz, Charity Alfredo, Loide Cossa, Nilesh Bhatt, Emilia H. Koumans, Chunfu Yang, Emilia Rivadeneira, Ilesh Jani, James C. Houston, Francesca Ceccherini-Silberstein.
Quantitative plasma viral load (VL) at 1000 copies /mL was recommended as the threshold to confirm antiretroviral therapy (ART) failure by the World Health Organization (WHO). Because of ongoing challenges of using plasma for VL testing in resource-limited settings (RLS), especially for children, this study collected 717 DBS and paired plasma samples from children receiving ART ≥1 year in Mozambique and compared the performance of DBS using Abbott’s VL test with a paired plasma sample using Roche’s VL test. At a cut-off of 1000 copies/mL, sensitivity of DBS using Abbott DBS VL test was 79.9%, better than 71.0% and 63.9% at 3000 and 5000 copies/mL, respectively. Specificities were 97.6%, 98.8%, 99.3% at 1000, 3000, and 5000 copies/mL, respectively. The Kappa value at 1000 copies/mL, 0.80 (95% CI: 0.73, 0.87), was higher than 0.73 (95% CI: 0.66, 0.80) and 0.66 (95% CI: 0.59, 0.73) at 3000, 5000 copies/mL, respectively, also indicating better agreement. The mean difference between the DBS and plasma VL tests with 95% limits of agreement by Bland-Altman was 0.311 (-0.908, 1.530). Among 73 children with plasma VL between 1000 to 5000 copies/mL, the DBS results were undetectable in 53 at the 1000 copies/mL threshold. While one DBS sample in the Abbott DBS VL test may be an alternative method to confirm ART failure at 1000 copies/mL threshold when a plasma sample is not an option for treatment monitoring, because of sensitivity concerns between 1,000 and 5,000 copies/ml, two DBS samples may be preferred accompanied by careful patient monitoring and repeat testing.
In 2013, WHO recommended monitoring quantitative viral load (VL) as the preferred approach to diagnose antiretroviral treatment (ART) failure; plasma HIV viral load of 1000 copies/ml was recommended as the threshold [1, 2]. However, in resource-limited settings (RLS), using plasma for VL testing presents substantial challenges because of the stringent collection and processing requirements including whole blood collection by venipuncture, plasma separation, cold chain transportation within limited hours, and appropriate short and long-term plasma storage. Using plasma for VL testing is especially challenging for small children since venipuncture is more difficult and experienced phlebotomists are often not available.
Table 1 summarizes the demographic and clinical information of the 723 enrolled children; 717 (99.2%) provided paired plasma and FS-DBS samples and 713 had complete demographic information. The mean age at enrollment was 8 years and 6 months and 45.9% of these children were female (Table 1).
In order to reach the ambitious 90-90-90 global goals, with 90 percent of people with HIV diagnosed, 90 percent on ART, and 90 percent virally suppressed by 2020 (UNAIDS, 2013), more people with HIV in RLS will need to initiate and stay on ART, and more of them will need active ART management and access to detection of treatment failure. Because conventional VL testing using plasma is often unavailable or impractical in RLS, use of a DBS sample is a feasible and practical alternative. Therefore, it is important to understand the potential limitations of using DBS for VL testing, especially for the WHO recommended treatment failure threshold. In this study, the performance of one FS-DBS spot to determine HIV treatment failure was evaluated using paired DBS and plasma samples from children on ART in Mozambique.
This research has been supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention. This information is distributed solely for the purpose of predissemination peer review under applicable information quality guidelines. It has not been formally disseminated by the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry, Atlanta, Georgia, USA. Instituto Nacional de Saúde (INS), Maputo Central Hospital, Ministry of Health Fundação Ariel Glaser contra o SIDA Pediátrico (Ariel). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention. Use of trade names is for identification purposes only and does not constitute endorsement by the U.S. Centers for Disease Control.