Search | About MonogramHIV.com | Monogram Biosciences, Inc. Trofile PhenoSense GT PhenoSense HIV GeneSeq HIV Assay Overview Technology HIV-1 Subtyping Report Form PhenoSense Entry PhenoSense Integrase Replication Capacity (RC) New Technologies Interpretation Support HIV Treatment Continuum Educational Tools Reimbursement Support Ordering a Test Report Form Footnotes The following footnotes are found on the report forms for PhenoSense GT™, PhenoSense™ HIV and GeneSeq™ HIV. Please click on the respective links below to view the supporting data or information for each footnote. PhenoSense GT Footnotes § For more information about FTC cutoff and HIV-1 subtype. * Nucleotide RT inhibitor. Clinical trial data from Gilead show intermediate responses in some patients up to a 4-fold change in susceptibility. (TFV cutoff) ‡ Clinical cutoff and genotypic interpretation algorithm derived from studies using IDV 800mg + RTV 200mg Q12h. PhenoSense HIV Footnotes § For more information about FTC cutoff. * Nucleotide RT inhibitor. Clinical trial data from Gilead show intermediate responses in some patients up to a 4-fold change in susceptibility. (TFV cutoff) ‡ Clinical cutoff derived from studies using IDV 800mg + RTV 200mg Q12h. GeneSeq HIV Footnotes § For more information about HIV-1 subtype. * Assessment of drug susceptibility is based upon detected mutations and interpreted using an advanced proprietary algorithm (version 3). ‡ Interpretation algorithm derived from studies using IDV 800mg + RTV 200mg Q12h. FTC Cutoff The following clinical study provides supporting data to establish the cutoff. Borroto-Esoda K, Miller M, Petropoulos C, and Parkin N. A Comparison of the Phenotypic Susceptibility Profiles of Emtricitabine (FTC) and Lamivudine (3TC). 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC. October 2004. Back to top IDV/r Cutoff The following clinical study provides supporting data to establish the cutoff. Szumiloski J, Wilson H, Campo R, Miller N, Rice H, Zolopa A, Klein D, Horberg M, Hellmann N, Bates M, and Condra J. Determination of an Indinavir Susceptibility Cutoff for Indinavir-Ritonavir-Containing Regimens. 10th Conference on Retroviruses and Opportunistic Infections, Boston, MA. February 2003. Back to top TFV Cutoff The following clinical study provides supporting data to establish the cutoff. Miller M, Margot N, Lu B, Zhong L, Chen S, Cheng A, and Wulfsohn M. Genotypic and Phenotypic Predictors of the Magnitude of Response to Tenofovir Disoproxil Fumarate Treatment in Antiretroviral-Experience Patients. J Infect Dis 2004; 189:837-46. Back to top Proprietary Algorithm Monogram is an established leader in the HIV drug resistance research field and regularly updates the genotypic interpretation algorithms used for its assays. Version 3 was implemented in May 2003. Back to top Genotypic Interpretation Algorithm for IDV/r The following clinical study provides supporting data to establish the algorithm. Chappey C, Petropoulos C, and Parkin N. Genotype Interpretation Algorithm for Predicting Monogramal Response in HIV-1 Infected Patients Receiving Ritonavir-Boosted Indinavir. 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, CA. February 2004. Back to top HIV-1 Subtype Monogram (Colombe Chappey, PhD) designed a computer algorithm that assigns subtype to a patient sample based on protease and reverse transcriptase sequence information. The patient sequence is compared to 3 distinct sets of partial-length reference sequences, each set containing a particular region from the reference sequences: Set 1- the region encompassing PR (300 nucleotides) Set 2- the region encompassing the first 453 nucleotides of RT Set 3- the region encompassing the next 462 nucleotides of RT Two methods of genetic sequence comparison are employed: BLAST and an in-house program (Align) that completes the local alignment generated by BLAST to generate a full-length alignment. These methods compare each patient sequence to the same 3 regions of a collection of reference sequences, containing 3 representatives of each subtype and recognized CRF. A similarity score (based on the number of nucleotide matches and the length of the alignment) is returned measuring how similar a given reference sequence (in a given region) is to the patient sequence. The reference sequences are then sorted based on the similarity score, and the subtype of the 2 closest reference sequences for each of the 3 regions is tabulated. Because each sequence will be compared successively to the 3 regions of the reference sequences, using BLAST and Align methods, and because the 2 closest reference sequences are returned for each of the 3 comparisons, the total number of closest reference sequences is 12. A subtype is assigned to the sample as follows: One of the major subtypes, when the sample PR/RT genome aligns most closely to a reference of that subtype in 9 of the 12 results; designated by one letter: A, B, C, D, F, G, H, J, or K A CRF represented by two letters (AE, AG, BF, etc), when the sample is locally closest to a CRF reference Two subtypes (A/C, A/D, etc) designated by 2 letters separated by a slash, when the sample is locally closest to 2 distinct subtypes "Complex" when the sample is equally close to 3 or more distinct subtypes Back to top Get the latest information on individualized medicine Notice of HIPAA Practices | Privacy Policy | Code of Ethics | Health Disclaimer | Site Map | Home | Contact Us | MonogramBio.com © 2006 Monogram Biosciences, Inc.