scholarly journals Implementation of an interactive mobile application to pilot a rapid assay to detect HIV drug resistance mutations in Kenya

Author(s):  
Justin D Vrana ◽  
Nuttada Panpradist ◽  
Nikki Higa ◽  
Daisy Ko ◽  
Parker Ruth ◽  
...  

Introduction: Usability is an overlooked aspect of implementing lab-based assays, particularly novel assays in low-resource-settings. Esoteric instructions can lead to irreproducible test results and patient harm. To address these issues, we developed a software application based on ″Aquarium″, a laboratory-operating system run on a computer tablet that provides step-by-step digital interactive instructions, protocol management, and sample tracking. Aquarium was paired with a near point-of-care HIV drug resistance test, ″OLA-Simple″, that detects mutations associated with virologic failure. In this observational study we evaluated the performance of Aquarium in guiding untrained users through the multi-step laboratory protocol with little supervision. Methods: A feasibility study was conducted in a laboratory at Coptic Hope Center in Nairobi, Kenya. To evaluate the training by Aquarium software, twelve volunteers who were unfamiliar with the kit performed the test on blinded samples (2 blood specimens; 5 codons/sample). Steps guided by Aquarium included: CD4+ T-Cell separation, PCR, ligation, detection, and interpretation of test results. Participants filled out a short survey regarding their demographics and experience with the software and kit. Results and discussion: 12/12 laboratory technicians had no prior experience performing CD4+ separation and 7/12 had no experience performing laboratory-based molecular assays. 12/12 isolated CD4+ T cells from whole blood with yields comparable to isolations performed by trained personnel. The OLA-Simple workflow was completed by all, with correct visual and software interpretation of results for 90% (108/120) and 97% (116/120) of codons, respectively. In the surveys, participants favorably assessed the use of software guidance. Conclusions: Aquarium digital instructions enabled first-time users in Kenya to complete the OLA-simple kit workflow with minimal training. Aquarium could increase the accessibility of laboratory assays in low-resource-settings and potentially standardize implementation of clinical laboratory tests.

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149215 ◽  
Author(s):  
Xi Chen ◽  
Xiaobai Zou ◽  
Jianmei He ◽  
Jun Zheng ◽  
Jennifer Chiarella ◽  
...  

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 264
Author(s):  
Miaomiao Li ◽  
Shujia Liang ◽  
Chao Zhou ◽  
Min Chen ◽  
Shu Liang ◽  
...  

Patients with antiretroviral therapy interruption have a high risk of virological failure when re-initiating antiretroviral therapy (ART), especially those with HIV drug resistance. Next-generation sequencing may provide close scrutiny on their minority drug resistance variant. A cross-sectional study was conducted in patients with ART interruption in five regions in China in 2016. Through Sanger and next-generation sequencing in parallel, HIV drug resistance was genotyped on their plasma samples. Rates of HIV drug resistance were compared by the McNemar tests. In total, 174 patients were included in this study, with a median 12 (interquartile range (IQR), 6–24) months of ART interruption. Most (86.2%) of them had received efavirenz (EFV)/nevirapine (NVP)-based first-line therapy for a median 16 (IQR, 7–26) months before ART interruption. Sixty-one (35.1%) patients had CRF07_BC HIV-1 strains, 58 (33.3%) CRF08_BC and 35 (20.1%) CRF01_AE. Thirty-four (19.5%) of the 174 patients were detected to harbor HIV drug-resistant variants on Sanger sequencing. Thirty-six (20.7%), 37 (21.3%), 42 (24.1%), 79 (45.4%) and 139 (79.9) patients were identified to have HIV drug resistance by next-generation sequencing at 20% (v.s. Sanger, p = 0.317), 10% (v.s. Sanger, p = 0.180), 5% (v.s. Sanger, p = 0.011), 2% (v.s. Sanger, p < 0.001) and 1% (v.s. Sanger, p < 0.001) of detection thresholds, respectively. K65R was the most common minority mutation, of 95.1% (58/61) and 93.1% (54/58) in CRF07_BC and CRF08_BC, respectively, when compared with 5.7% (2/35) in CRF01_AE (p < 0.001). In 49 patients that followed-up a median 10 months later, HIV drug resistance mutations at >20% frequency such as K103N, M184VI and P225H still existed, but with decreased frequencies. The prevalence of HIV drug resistance in ART interruption was higher than 15% in the survey. Next-generation sequencing was able to detect more minority drug resistance variants than Sanger. There was a sharp increase in minority drug resistance variants when the detection threshold was below 5%.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Gweneth B. Lazenby ◽  
Okeoma Mmeje ◽  
Barbra M. Fisher ◽  
Adriana Weinberg ◽  
Erika K. Aaron ◽  
...  

Objective. To compare HIV drug resistance in pregnant women with perinatal HIV (PHIV) and those with nonperinatal HIV (NPHIV) infection.Methods. We conducted a multisite cohort study of PHIV and NPHIV women from 2000 to 2014. Sample size was calculated to identify a fourfold increase in antiretroviral (ARV) drug resistance in PHIV women. Continuous variables were compared using Student’st-test and Wilcoxon rank-sum tests. Categorical variables were compared usingχ2and Fisher’s exact tests. Univariate analysis was used to determine factors associated with antiretroviral drug resistance.Results. Forty-one PHIV and 41 NPHIV participants were included. Women with PHIV were more likely to have drug resistance than those with NPHIV ((55% versus 17%,p=0.03), OR 6.0 (95% CI 1.0–34.8),p=0.05), including multiclass resistance (15% versus 0,p=0.03), and they were more likely to receive nonstandard ARVs during pregnancy (27% versus 5%,p=0.01). PHIV and NPHIV women had similar rates of preterm birth (11% versus 28%,p=0.08) and cesarean delivery (47% versus 46%,p=0.9). Two infants born to a single NPHIV woman acquired HIV infection.Conclusions. PHIV women have a high frequency of HIV drug resistance mutations, leading to nonstandard ARVs use during pregnancy. Despite nonstandard ARV use during pregnancy, PHIV women did not experience increased rates of adverse pregnancy outcomes.


2019 ◽  
Vol 33 (3) ◽  
pp. 707-742 ◽  
Author(s):  
Suzanne M. McCluskey ◽  
Mark J. Siedner ◽  
Vincent C. Marconi

2019 ◽  
Vol 74 (10) ◽  
pp. 3016-3020 ◽  
Author(s):  
Godfrey Barabona ◽  
Macdonald Mahiti ◽  
Salim Masoud ◽  
Peter Mbelele ◽  
Amina Shaban Mgunya ◽  
...  

Abstract Objectives We investigated the prevalence and patterns of pre-treatment and acquired HIV drug resistance mutations (DRMs) in Tanzania as a ‘treat all’ strategy, virological monitoring and the progressive increase in usage of tenofovir are being implemented in HIV treatment programmes. Methods Viral RNA was isolated from plasma of 60 ART-naive and 166 treated-but-viraemic (>400 copies/mL) HIV-1-infected adults attending a care and treatment clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania, between June and October 2017. Viral genes encoding protease and reverse transcriptase were amplified by PCR and directly sequenced. Results Viral genotyping of successfully amplified samples revealed pre-treatment DRMs in 14/47 (29.8%) ART-naive subjects. Of these, 7/47 (14.9%) harboured mutations that confer high-level resistance to at least one drug of the default first-line regimen. In treated-but-viraemic subjects, DRMs were found in 100/111 (90%), where DRMs against NNRTI, NRTI and PI were observed in 95/100 (95%), 92/100 (92%) and 13/100 (13%), respectively. Tenofovir-resistance mutations K65R and K70G/E or ≥3 thymidine analogue resistance mutations including M41L and L210W were found in 18/36 (50%) subjects on a tenofovir-containing regimen at failure. Four patients harboured multiple DRMs, which can confer resistance to all available ART regimens in Tanzania. Conclusions Taken together, pre-treatment and acquired DRMs were highly prevalent, which represents a major risk for the efficacy of ART programmes in Tanzania. Availability of a newer generation of antiretroviral drugs with a higher genetic barrier to resistance and robust treatment monitoring is warranted for effective and sustainable HIV treatment.


Sign in / Sign up

Export Citation Format

Share Document