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ucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitor resistance-associated mutations were defined according to International Antiviral Society USA Guidelines from March 2013. HIV RT and protease for the pre-therapy time-point was also analyzed by UDS as performed by 454 Life Sciences/Roche using proprietary primers. The HIV sequences analyzed by UDS included protease AA 1099 and RT AA 1-251. Median UDS sample read depth over all amino acid positions was 3273 reads and frequency results were censored at $1% with a read depth $100. Quest Diagnostics performed all other laboratory tests. HIV RNA concentrations were measured by the Roche Cobas Amplicor HIV-1 Monitor or Ultrasensitive Monitor Test. Clade analysis was performed using RIP 3.0. RIP was configured to perform query alignments against the HIV database standard HIV-1 subtype consensus alignments. Each pol sequence was analyzed with a sliding window of decreasing sizes 200,150, and 100 nucleotides until a subtype could be determined or was marked as unknown. Materials and Methods Ethics Statement All study subjects provided written informed consent. This study was approved by the ethics review boards used by for the 72 participating centers, which included Ethica Clinical Research Inc., MUHC Biomedical D, Sunnybrook Health Sciences Centre Research Ethics Board, University Hth Network Res Ethics B, Copernicus Group IRB, Henry Ford Hth System Res Administration, U of South Florida IRB, U and Medical CTR IRB of East Carolina U, U of Toledo Department for Human Res Protections Biomedical IRB, Whitman-Walker Clinic IRB, Summa Hth S Hospitals IRB, Western IRB, U of Kentucky Office of Res Integrity, HU Subjects Res Committee, Florida Dept of Hth IRB, Kaiser Permanente CTR for PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19631915 Hth Res/Southeast, U of Southern California Hth Sciences Campus IRB, Georgetown University IRB, St. Joseph’s Hp IRB, Chesapeake Research Review, Inc., U of Texas Med Branch O of Res SU P IRB, Loyola U Med CTR IRB for the P of HU SU, Washington U in St. Louis HU Res P O, U of Chicago IRB, U of Southern California School of Medicine IRB, Partners HU Res O, New York Med College Committee for P of HU SU, Thomas Jefferson IRB, Miriam Hp Clinical Res RB, U of Pennsylvania IRB, and the AIDS Res Consortium of Atlanta, Inc. IRB. This study was conducted in accordance with Good Clinical Practice. Study Design Blood plasma-derived HIV samples used in the genotypic analysis were obtained from HIV-infected, ART-naive subjects during their screening visit to determine eligibility for study enrollment in ARIES. HIV genotyping was performed prospectively on all subjects at screening as an appropriate HIV ART-Naive HIV-1 Phylogenetic Clustering Patterns Phylogenetic Reconstruction and VTC Prediction HIV-1 RT and protease nucleotide sequences obtained by population genotype sequencing from ART-naive subjects at the screening visit were concatenated and subsequently aligned using the software MUSCLE. The resulting alignment was used to BQ 123 web reconstruct a neighbor joining PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19632179 tree using the programs DNADIST and NEIGHBOR from the PHYLIP 3.67 package. In estimating genetic distances, the F84 model incorporates different rates of transition and transversion and also allows for different frequencies of the four nucleotides. HIV-1 Subtype K sequence AJ24935 was used as an outgroup for the tree and 1000 bootstrap replicates were used to estimate node support. A VTC was defined as any operatin

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Author: M2 ion channel