Management of Virologic Failure and HIV Drug Resistance

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.

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Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial

Clinical Infectious Diseases ◽

10.1093/cid/civ102 ◽

2015 ◽

Vol 60 (10) ◽

pp. 1541-1549 ◽

Cited By ~ 51

Author(s):

Rami Kantor ◽

Laura Smeaton ◽

Saran Vardhanabhuti ◽

Sarah E. Hudelson ◽

Carol L. Wallis ◽

...

Keyword(s):

Clinical Trial ◽

Drug Resistance ◽

Virologic Failure ◽

Subtype C ◽

Hiv Drug Resistance ◽

Hiv 1

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HIV Drug Resistance Mutations (DRMs) Detected by Deep Sequencing in Virologic Failure Subjects on Therapy from Hunan Province, China

PLoS ONE ◽

10.1371/journal.pone.0149215 ◽

2016 ◽

Vol 11 (2) ◽

pp. e0149215 ◽

Cited By ~ 8

Author(s):

Xi Chen ◽

Xiaobai Zou ◽

Jianmei He ◽

Jun Zheng ◽

Jennifer Chiarella ◽

...

Keyword(s):

Drug Resistance ◽

Deep Sequencing ◽

Virologic Failure ◽

Hunan Province ◽

Resistance Mutations ◽

Hiv Drug Resistance ◽

Drug Resistance Mutations

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HIV drug resistance detected during low-level viraemia is associated with subsequent virologic failure

AIDS ◽

10.1097/qad.0000000000000203 ◽

2014 ◽

Vol 28 (8) ◽

pp. 1125-1134 ◽

Cited By ~ 37

Author(s):

Luke C. Swenson ◽

Jeong Eun Min ◽

Conan K. Woods ◽

Eric Cai ◽

Jonathan Z. Li ◽

...

Keyword(s):

Drug Resistance ◽

Virologic Failure ◽

Hiv Drug Resistance ◽

Low Level

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Epidemiology of human immunodeficiency virus (HIV) drug resistance in HIV patients with virologic failure of first‐line therapy in the country of Georgia

Journal of Medical Virology ◽

10.1002/jmv.25245 ◽

2018 ◽

Vol 91 (2) ◽

pp. 235-240 ◽

Cited By ~ 3

Author(s):

Ekaterine Karkashadze ◽

Natia Dvali ◽

Natalia Bolokadze ◽

Lali Sharvadze ◽

Pati Gabunia ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Drug Resistance ◽

Virologic Failure ◽

First Line ◽

Hiv Patients ◽

Hiv Drug Resistance ◽

First Line Therapy ◽

Line Therapy ◽

Immunodeficiency Virus ◽

Country Of Georgia

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Genotypic Methods for HIV Drug Resistance Monitoring: The Opportunities and Challenges Faced by China

Current HIV Research ◽

10.2174/1570162x17666190927154110 ◽

2019 ◽

Vol 17 (4) ◽

pp. 225-239 ◽

Cited By ~ 2

Author(s):

Lulu Zuo ◽

Ke Peng ◽

Yihong Hu ◽

Qinggang Xu

Keyword(s):

Drug Resistance ◽

Virological Suppression ◽

Testing Methods ◽

Hiv Drug Resistance ◽

Advantages And Disadvantages ◽

Hiv Epidemic ◽

Routine Surveillance ◽

The World ◽

Global Project ◽

Hiv 1

AIDS is a globalized infectious disease. In 2014, UNAIDS launched a global project of “90-90-90” to end the HIV epidemic by 2030. The second and third 90 require 90% of HIV-1 infected individuals receiving antiretroviral therapy (ART) and durable virological suppression. However, wide use of ART will greatly increase the emergence and spreading of HIV drug resistance and current HIV drug resistance test (DRT) assays in China are seriously lagging behind, hindering to achieve virological suppression. Therefore, recommending an appropriate HIV DRT method is critical for HIV routine surveillance and prevention in China. In this review, we summarized the current existing HIV drug resistance genotypic testing methods around the world and discussed the advantages and disadvantages of these methods.

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HIV Drug Resistance Testing in a Resource Limited Setting with High Viral Diversity: The First Twenty Eight Months Experience

Current HIV Research ◽

10.2174/1570162x15666170725143835 ◽

2017 ◽

Vol 15 (4) ◽

Cited By ~ 1

Author(s):

Elodie Teclaire Ngo-Malabo ◽

Paul Alain Ngoupo ◽

Serge Alain Sadeuh-Mba ◽

Emmanuel Akongnwi ◽

Robert Banaï ◽

...

Keyword(s):

Drug Resistance ◽

Resource Limited Setting ◽

Resistance Testing ◽

Viral Diversity ◽

Hiv Drug Resistance ◽

Drug Resistance Testing ◽

Resource Limited ◽

Limited Setting

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HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China

Pathogens ◽

10.3390/pathogens10030264 ◽

2021 ◽

Vol 10 (3) ◽

pp. 264

Author(s):

Miaomiao Li ◽

Shujia Liang ◽

Chao Zhou ◽

Min Chen ◽

Shu Liang ◽

...

Keyword(s):

Drug Resistance ◽

Next Generation Sequencing ◽

Antiretroviral Therapy ◽

Detection Threshold ◽

Next Generation ◽

Resistance Mutations ◽

Hiv Drug Resistance ◽

Drug Resistance Mutations ◽

Therapy Interruption ◽

Generation Sequencing

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%.

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Factors Influencing HIV Drug Resistance among Pregnant Women in Luanda, Angola: Findings from a Cross-Sectional Study

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6010029 ◽

2021 ◽

Vol 6 (1) ◽

pp. 29

Author(s):

Cruz S. Sebastião ◽

Joana Morais ◽

Miguel Brito

Keyword(s):

Drug Resistance ◽

Pregnant Women ◽

Rural Areas ◽

Cross Sectional Study ◽

Drug Resistant ◽

Sectional Study ◽

Cross Sectional ◽

Hiv Drug Resistance ◽

Hiv 1 ◽

High Educational

The increase in HIV infection and drug-resistant strains is an important public health concern, especially in resource-limited settings. However, the identification of factors related to the propagation of infectious diseases represents a crucial target offering an opportunity to reduce health care costs as well as deepening the focus on preventing infection in high-risk groups. In this study, we investigate the factors related to drug resistance among HIV-infected pregnant women in Luanda, the capital city of Angola. This was a part of a cross-sectional study conducted with 42 HIV-positive pregnant women. A blood sample was collected, and HIV-1 genotyping was carried out using an in-house method. Multivariate analyses were performed to determine the interaction between sociodemographic characteristics and drug resistance. HIV drug resistance was detected in 44.1% of the studied population. High probabilities of drug resistance were observed for HIV-infected pregnant women living in rural areas (AOR: 2.73; 95% CI: 0.50–14.9) with high educational level (AOR: 6.27; 95% CI: 0.77–51.2) and comorbidities (AOR: 5.47; 95% CI: 0.28–106) and infected with a HIV-1 non-B subtype other than subtype C (AOR: 1.60; 95% CI: 0.25–10.3). The present study reports high HIV drug resistance. Furthermore, older-age, rural areas, high educational levels, unemployed status, having comorbidities, and HIV-1 subtypes were factors related to drug resistance. These factors impact on drug susceptibility and need to be urgently addressed in order to promote health education campaigns able to prevent the spread of drug-resistant HIV strains in Angola.

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