Dataset Information

HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing.

ABSTRACT: The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.

SUBMITTER: Rhee SY

PROVIDER: S-EPMC4696791 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing.

Rhee Soo-Yon SY Jordan Michael R MR Raizes Elliot E Chua Arlene A Parkin Neil N Kantor Rami R Van Zyl Gert U GU Mukui Irene I Hosseinipour Mina C MC Frenkel Lisa M LM Ndembi Nicaise N Hamers Raph L RL Rinke de Wit Tobias F TF Wallis Carole L CL Gupta Ravindra K RK Fokam Joseph J Zeh Clement C Schapiro Jonathan M JM Carmona Sergio S Katzenstein David D Tang Michele M Aghokeng Avelin F AF De Oliveira Tulio T Wensing Annemarie M J AM Gallant Joel E JE Wainberg Mark A MA Richman Douglas D DD Fitzgibbon Joseph E JE Schito Marco M Bertagnolio Silvia S Yang Chunfu C Shafer Robert W RW

PloS one 20151230 12

The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treat ...[more]

PMID: 26717411

Similar Datasets

Project description:BackgroundHIV/AIDS remains one of the major global human health challenges, especially in resource-limited environments. By 2017, over 77.3 million people were infected with the disease, and approximately 35.4 million individuals had already died from AIDS-related illnesses. Approximately 21.7 million people were accessing ART with significant clinical outcomes. However, numerous challenges are experienced in the delivery and accurate interpretation of data on patients with HIV data by various health care providers at different care levels. Mobile health (mHealth) technology is progressively making inroads into the health sector as well as medical research. Different mobile devices have become common in health care settings, leading to rapid growth in the development of downloadable software specifically designed to fulfill particular health-related purposes.ObjectiveWe developed a mobile-based app called ARVPredictor and demonstrated that it can accurately define HIV-1 drug-resistance mutations in the HIV pol gene for use at the point of care.MethodsARVPredictor was designed using Android Studio with Java as the programming language and is compatible with both Android and iOS. The app system is hosted on Nginx Server, and network calls are built on PHP's Laravel framework handled by the Retrofit Library. The DigitalOcean offers a high-performance and stable cloud computing platform for ARVPredictor. This mobile app is enlisted in the Google Play Store as an "ARVPredictor" and the source code is available under MIT permissive license at a GitHub repository. To test for agreement between the ARVPredictor and Stanford HIV Database in detecting HIV subtype and NNRT and NRTI mutations, a total of 100 known HIV sequences were evaluated.ResultsThe mobile-based app (ARVPredictor) takes in a set of sequences or known mutations (protease, reverse transcriptase and integrase). It then returns inferred levels of resistance to selected nucleoside, nonnucleoside protease, and integrase inhibitors for accurate HIV/AIDS management at the point of care. The ARVPredictor identified similar HIV subtypes in 98/100 sequences compared with the Stanford HIV Database (κ=0.98, indicating near perfect agreement). There were 89/100 major NNRTI and NRTI mutations identified by ARVPredictor, similar to the Stanford HIV Database (κ=0.89, indicating near perfect agreement). Eight mutations classified as major by the Stanford HIV Database were classified as others by ARVPredictor.ConclusionsThe ARVPredictor largely agrees with the Stanford HIV Database in identifying both major and minor proteases, reverse transcriptase, and integrase mutations. The app can be conveniently used robustly at the point of care by HIV/AIDS care providers to improve the management of HIV infection.

Project description:BackgroundFeasible, scalable, and cost-effective approaches to ensure virological suppression among children living with HIV are urgently needed. The aim of the Opt4Kids study was to determine the effect of point of care viral load and targeted drug resistance mutation testing in improving virological suppression among children on antiretroviral therapy (ART) in Kenya.MethodsIn this open-label, individually randomised controlled trial, we enrolled children living with HIV aged 1-14 years and who were either newly initiating or already receiving ART at five study facilities in Kenya. Participants were randomly allocated 1:1 to receive the intervention of point-of-care viral load testing every 3 months, targeted drug resistance mutation testing, and clinical decision support (point-of-care testing) or to receive the standard care (control group), stratified by facility site and age groups (1-9 years vs 10-14 years). Investigators were masked to the randomised group. The primary efficacy outcome was virological suppression (defined as a viral load of <1000 copies per mL) by point-of-care viral load testing at 12 months after enrolment in all participants with an assessment. This study is registered with ClinicalTrials.gov, NCT03820323.FindingsBetween March 7, 2019, and December 31, 2020, we enrolled 704 participants. Median age at enrolment was 9 years (IQR 7-12), 344 (49%) participants were female and 360 (51%) were male, and median time on ART was 5·8 years (IQR 3·1-8·6). 536 (76%) of 704 had documented virological suppression at enrolment. At 12 months after enrolment, the proportion of participants achieving virological suppression in the intervention group (283 [90%] of 313 participants with a 12 month point-of-care viral load test) did not differ from that in the control group (289 [92%] of 315; risk ratio [RR] 0·99, 95% CI 0·94-1·03; p=0·55). We identified 138 episodes of viraemia in intervention participants, of which 107 (89%) samples successfully underwent drug resistance mutation testing and 91 (85%) had major drug resistance mutations. The median turnaround time for viral load results was 1 day (IQR 0-1) in the intervention group and 15 days (10-21) in the control group.InterpretationPoint-of-care viral load testing decreased turnaround time and targeted drug resistance mutation testing identified a high prevalence of HIV drug resistance mutations in children living with HIV, but the combined approach did not increase rates of virological suppression. Further research in combination interventions, including point-of-care viral load and drug resistance mutation testing coupled with psychosocial support, is needed to optimise virological suppression for children living with HIV.FundingNational Institutes of Mental Health of the US National Institutes of Health, Thrasher Research Fund.

Project description:Significant numbers of human immunodeficiency virus (HIV) infections are transmitted unknowingly, making efforts to increase HIV testing accessibility crucial. As trusted healthcare providers, pharmacists can increase accessibility of HIV screening and referral services. However, challenges with lack of private counseling and testing space, need for training and education, lack of adequate staffing, heavy workload, and uncertainty supporting patients with reactive results have been previously reported by community pharmacists as barriers to offering HIV screening. The objective of this study was to investigate pharmacists' opinions of strategies for addressing these barriers. A survey was developed to gather information regarding steps that could be taken to increase pharmacist comfort and interest offering HIV point-of-care testing (POCT) services. Thirty pharmacies were contacted and representatives from twenty-six responded. Pharmacists reported that they were likely or very likely to offer HIV POCT if they were given the following: a 2 h training session on administering and interpreting HIV POCT (73%); a 4 h education session on a variety of HIV education topics (73%); training about couples testing, post-test counseling, and de-escalation techniques (58%); or a semi-annual CE training (58%). Pharmacist respondents were likely or very likely (81%) to implement HIV POCT if there was a protocol in place so that patients with a reactive screening would out be referred for diagnostic testing and if there was a script provided as a template for post-test counseling (81%). The majority of pharmacists (69%) also preferred the appointment-based model rather than a walk-in or combination option and preferred (77%) having 20-30 min of dedicated time with the patient to provide adequate testing, education, and counseling. By using these strategies to improve comfort and likelihood implementing HIV POCT, pharmacists can increase access to HIV testing and decrease the spread of HIV.

Dataset Information

HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing.

Publications

HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets