a combined screening platform for hiv treatment failure and resistance联合筛查艾滋病毒治疗失败和阻力的平台.pdfVIP

A Combined Screening Platform for HIV Treatment Failure and Resistance 1 3 ´ ´ 5 1 1 Myres W. Tilghman *, Susanne May , Josue Perez-Santiago , Caroline C. Ignacio , Susan J. Little , Douglas D. Richman1,2,4, Davey M. Smith1,2* 1 Department of Medicine, University of California San Diego, La Jolla, California, United States of America, 2 Veterans Affairs San Diego Healthcare System, San Diego, California, United States of America, 3 Department of Biostatistics, University of Washington, Seattle, Washington, United States of America, 4 Department of Pathology, University of California San Diego, La Jolla, California, United States of America, 5 Department of Bioinformatics and Systems Biology, University of California San Diego, La Jolla, California, United States of America Abstract Background: 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. Methods: 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. Results: Of 295 samples analyzed, 43 (15%) had v