A combined screening platform for HIV treatment failure and resistance.

PloS One
Myres W TilghmanDavey M Smith

Abstract

To develop a low cost method to screen for virologic failure of antiretroviral therapy (ART) and HIV-1 drug resistance, we performed a retrospective evaluation of a screening assay using serial dilutions of HIV-1 RNA-spiked blood plasma and samples from patients receiving >6 months of first-line ART. Serial dilution testing was used to assess sensitivity of a simple PCR-based assay (targeted at ≥1,000 HIV RNA copies/mL). We created blood plasma minipools of five samples, extracted HIV RNA from the pools, PCR amplified the reverse transcriptase (RT) coding region of the HIV-1 pol gene from extracted RNA, sequenced PCR product of positive pools, and used sequences to determine drug resistance. Sensitivity, specificity, and predictive values were determined for different levels of virologic failure based on maximum viral loads of individual samples within a pool. Of 295 samples analyzed, 43 (15%) had virologic failure at ≥50 copies/mL (range 50-10,500 copies/mL, four at ≥1,000 copies/mL). The assay demonstrated 100% sensitivity to detect virus from these four samples, requiring only one round of PCR, and 56% and 89% sensitivity to detect samples with ≥50 and ≥500 copies/mL using two rounds. Amplified PCR products of all positive p...Continue Reading

References

Feb 17, 2005·JAMA : the Journal of the American Medical Association·Richard E NettlesRobert F Siliciano
Aug 22, 2006·The Journal of Infectious Diseases·Robert W Shafer
Sep 23, 2009·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Susanne MayDavey M Smith
Jul 20, 2010·JAMA : the Journal of the American Medical Association·Melanie A ThompsonUNKNOWN International AIDS Society-USA
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Feb 4, 2011·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·G U van ZylD Smith

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Citations

Jun 16, 2014·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Howard NewmanWolfgang Preiser
Jan 23, 2013·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Rafia S RasuKathy Goggin
Jul 3, 2015·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Myres TilghmanDavey M Smith
Sep 16, 2014·Bioscience Reports·Jun-Jie Poh, Samuel Ken-En Gan
Jan 10, 2018·Journal of Viral Hepatitis·T R DineshaS Saravanan
Sep 17, 2020·African Journal of Laboratory Medicine·Wolfgang Preiser, Gert U van Zyl
Sep 27, 2020·Reviews in Medical Virology·Howard Newman, Diana Hardie

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Methods Mentioned

BETA
genotyping
PCR
electrophoresis

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