Current Status of Point-of-Care Testing for Human Immunodeficiency Virus Drug Resistance

Duarte, Horacio A.; Panpradist, Nuttada; Beck, Ingrid; Lutz, Barry; Lai, James J.; Kanthula, Ruth; Kantor, Rami; Tripathi, Anubhav; Saravanan, S.; MacLeod, Iain J.; Chung, Michael H.; Zhang, Guoqing; Yang, Chunfu; Frenkel, Lisa M.

doi:10.1093/infdis/jix413

Cited by 23 publications

(19 citation statements)

References 36 publications

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“…The shift towards more rapid initiation of ART (including same-day initiation) would make it particularly challenging to deliver pretreatment HIVDR testing. We still lack simple, rapid, and inexpensive HIVDR assays, although there are promising technologies in development [69]. Given the increasing complexity of HIV care and the uncertainty about the long-term effectiveness of DTG-based regimens, there is still a need to develop and evaluate HIVDR assays and pretreatment HIVDR testing strategies.…”

Section: Discussionmentioning

confidence: 99%

Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000–2016: A Pooled Sequence Analysis

et al. 2019

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Background South Africa has the largest public antiretroviral therapy (ART) programme in the world. We assessed temporal trends in pretreatment HIV-1 drug resistance (PDR) in ART-naïve adults from South Africa. Methods We included datasets from studies conducted between 2000 and 2016, with HIV-1 pol sequences from more than ten ART-naïve adults. We analysed sequences for the presence of 101 drug resistance mutations. We pooled sequences by sampling year and performed a sequence-level analysis using a generalized linear mixed model, including the dataset as a random effect. Findings We identified 38 datasets, and retrieved 6880 HIV-1 pol sequences for analysis. The pooled annual prevalence of PDR remained below 5% until 2009, then increased to a peak of 11·9% (95% confidence interval (CI) 9·2-15·0) in 2015. The pooled annual prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR remained below 5% until 2011, then increased to 10.0% (95% CI 8.4–11.8) by 2014. Between 2000 and 2016, there was a 1.18-fold (95% CI 1.13–1.23) annual increase in NNRTI PDR (p < 0.001), and a 1.10-fold (95% CI 1.05–1.16) annual increase in nucleoside reverse-transcriptase inhibitor PDR (p = 0.001). Interpretation Increasing PDR in South Africa presents a threat to the efforts to end the HIV/AIDS epidemic. These findings support the recent decision to modify the standard first-line ART regimen, but also highlights the need for broader public health action to prevent the further emergence and transmission of drug-resistant HIV. Source of Funding This research project was funded by the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support Package. Disclaimer The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CDC.

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Section: Discussionmentioning

confidence: 99%

Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000–2016: A Pooled Sequence Analysis

et al. 2019

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“…In LMICs, the management of PLHIV who are identified as having unsuppressed HIV viral loads is complicated by the lack of objective measures of drug adherence and HIV drug resistance, which continues to emerge in LMICs (221,224). The technological advances that have made POC NAAT available are also applicable to the development of POC HIV drug resistance assays that may allow for decentralized HIV resistance testing (225). Several assays are in development, while target mutations need to be fully characterized for specific drugs and drug regimens.…”

Section: Additional Diagnostics Needed For Hiv Monitoringmentioning

confidence: 99%

Point-of-Care HIV Viral Load Testing: an Essential Tool for a Sustainable Global HIV/AIDS Response

et al. 2019

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SUMMARY The global public health community has set ambitious treatment targets to end the HIV/AIDS pandemic. With the notable absence of a cure, the goal of HIV treatment is to achieve sustained suppression of an HIV viral load, which allows for immunological recovery and reduces the risk of onward HIV transmission. Monitoring HIV viral load in people living with HIV is therefore central to maintaining effective individual antiretroviral therapy as well as monitoring progress toward achieving population targets for viral suppression. The capacity for laboratory-based HIV viral load testing has increased rapidly in low- and middle-income countries, but implementation of universal viral load monitoring is still hindered by several barriers and delays. New devices for point-of-care HIV viral load testing may be used near patients to improve HIV management by reducing the turnaround time for clinical test results. The implementation of near-patient testing using these new and emerging technologies may be an essential tool for ensuring a sustainable response that will ultimately enable an end to the HIV/AIDS pandemic. In this report, we review the current and emerging technology, the evidence for decentralized viral load monitoring by non-laboratory health care workers, and the additional considerations for expanding point-of-care HIV viral load testing.

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“…Inexpensive and high-throughput focused resistance genotyping could provide cost savings for national ART programs as treatment access continues to expand and the number of patients switching to alternative regimens continues to grow. The best candidate assay for focused genotyping are point mutation assays (PMAs) (e.g., allele-specific PCR, oligonucleotide ligation assay, and probe-based quantitative real-time PCR [qPCR]) (16). PMAs have high detection sensitivities for single nucleotide polymorphisms (SNPs), however, are exquisitely sensitive to genetic variability near the SNP and return a false negative result in the presence of a secondary polymorphism (a proximal nucleotide change unrelated to drug resistance) (17).…”

Section: Introductionmentioning

confidence: 99%

PANDAA-monium: Intentional violations of conventional qPCR design enables rapid, HIV-1 subtype-independent drug resistance SNP detection

MacLeod

Rowley

Essex

2019

Preprint

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Global efforts to ensure that 90% of all HIV-infected people receiving antiretroviral therapy (ART) will be virally suppressed by 2020 could be crippled by increases in acquired and transmitted HIV drug resistance (HIVDR), which challenge ART efficacy. The long-term sustainability of ART treatment programs is contingent on effective HIVDR monitoring yet current Sanger sequencing genotypic resistance tests are inadequate for large-scale implementation in low-and middle-income countries (LMICs). A simple, rapid, affordable HIVDR diagnostic would radically improve the treatment paradigm in LMICs by facilitating informed clinical decision-making upon ART failure. Although point mutation assays can be broadly deployed in this context, the primary challenge arises from extensive sequence variation surrounding targeted drug resistance mutations (DRMs). Here, we systematically and intentionally violate the canonical principles of qPCR design to develop a novel assay, Pan-Degenerate Amplification and Adaptation (PANDAA), that mitigates the impact of DRM-proximal secondary polymorphisms on probe-based qPCR performance to enable subtype-independent, focused resistance genotyping. Using extremely degenerate primers with 3' termini overlapping the probe-binding site, the HIV-1 genome is adapted through site-directed mutagenesis to replace secondary polymorphisms flanking the target DRM during the initial qPCR cycles. We show that PANDAA can quantify key HIV DRMs present at ≥5% and has diagnostic sensitivity and specificity of 96.9% and 97.5%, respectively, to detect DRMs associated with ART failure. PANDAA is an innovative solution for HIVDR genotyping and is an advancement in qPCR technology that could be applicable to any scenario where target-proximal genetic variability has been a roadblock in diagnostic development.

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Current Status of Point-of-Care Testing for Human Immunodeficiency Virus Drug Resistance

Cited by 23 publications

References 36 publications

Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000–2016: A Pooled Sequence Analysis

Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000–2016: A Pooled Sequence Analysis

Point-of-Care HIV Viral Load Testing: an Essential Tool for a Sustainable Global HIV/AIDS Response

PANDAA-monium: Intentional violations of conventional qPCR design enables rapid, HIV-1 subtype-independent drug resistance SNP detection

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