Next Generation Deep Sequencing to Evaluate Viral Tropism in HIV-1 Patients Exposed to Maraviroc Add-On Therapy for 8 Days *Rachel A. McGovern, Art F.Y.

Slides:

Advertisements

Similar presentations

Durability of Response and Rate of Re-emergence of Wild Type at Boceprevir (BOC) Resistance-Associated Variant (RAV) Loci in Genotype 1a and 1b Patients:

Advertisements

Presentation for HL7 RCRIM and Clinical Genomics SIG HL7 Working Group Meeting San Diego, CA 21Jan2004.

16 th Conference on Retroviruses and Opportunistic Infections February 8-11, 2009 Palais des Congrès de Montréal Montréal, Canada Javier Martinez-Picado.

POSTER 82 CXCR4 using HIV-1 strains more abundant in PBMC than in plasma Chris Verhofstede 1 *, Linos Vandekerckhove 2, Veerle van Eygen 3, Kenny Dauwe.

Emerging patterns of drug resistance and viral tropism in cART-naïve and failing patients infected with HIV-1 subtype C Thumbi Ndung’u, BVM, PhD Associate.

Evoluzione genetica di HIV ed evoluzione clinica della malattia AIDS: due aspetti correlati? Carlo Federico Perno.

Antiviral Immunity and Transmission June 19, 2011 Abst. #: TUAA0105 Maraviroc-resistant subtype B primary HIV-1 induced in vitro selection became highly.

High rates of survival, virologic suppression and immune reconstitution among patients receiving second-line ART in the Indian national programme B.B.

HIV-1 escape from the CCR5 antagonist maraviroc associated with an altered and less efficient mechanism of gp-120 CCR5 engagement that attenuates macrophage.

Objective of the DAP A) Specify an analysis plan that can be applied to a wide variety of clinical HIV resistance studies. B) Include both Intervention.

1 Using Biostatistics to Evaluate Vaccines and Medical Tests Holly Janes Fred Hutchinson Cancer Research Center.

Salvage Antiretroviral Therapy Guiding Principles, Strategies and the Role of Resistance Testing.

An Introduction to the HIV Problem Space Oakwood University: Faculty Quantitative Institute Aug. 10–12, 2009.

The Namibia Treatment Literacy Approach: Empowering Patients with Knowledge on Antiretroviral Therapy Through Audiovisual Materials Authors Francis Kalemeera.

Abstract Results Objectives Results Conclusions Background Methods V-1637 Background-At the CORE center in Chicago, despite an on-site hepatitis clinic.

Autologous T-cell therapy based on a lentiviral vector expressing long antisense RNA targeted against HIV-1 env gene influences HIV replication and evolution.

1 Treatment Failure HAIVN Harvard Medical School AIDS Initiative in Vietnam.

CCR5 Monoclonal Antibody PRO 140 Inhibited HIV-1 Resistant to Maraviroc, a Small Molecule CCR5 Antagonist Andre J Marozsan Progenics Pharmaceuticals, Inc.

HIV-1 Resistance - Implications For Clinicians Joseph J. Eron Jr., MD Professor of Medicine University of North Carolina.

Poster # 388 CROI Feb Montreal, Canada Association of HIV-1 Co-receptor Tropism with Immunologic and Virologic Parameters in HIV-1 infected,

1 Resistance and Tropism - Maraviroc Lisa K. Naeger, Ph.D. Division of Antiviral Products Food and Drug Administration April 24, 2007 FDA Antiviral Advisory.

Phylodynamically Estimated HIV Diversification Rates Reveal Prevention of HIV-1 by Antiretroviral Therapy Jeffrey B. Joy, Richard H. Liang, Rosemary M.

Clinical case 19 Lin, I-Yao (Sally). Case 19 Having been confined in the hospital for almost a month due recurrent pneumonia, Mr. XXX, 42 y/o, married,

Efficacy and Safety of Maraviroc in Treatment- Experienced (TE) Patients Infected with R5 HIV-1: 96-week Combined Analysis of the MOTIVATE 1 & 2 Studies.

Monitoring HIV tropism and Maraviroc regimens in clinical routine - 24 weeks of follow-up data - Heribert Knechten, MD PZB Aachen, Germany T = 5.

Assay To Measure The Latent Reservoir Of Replication-Competent HIV-1 In Suppressed Patients Based On Ultra Deep Sequencing Sook-Kyung Lee.

HIV-1 Evolution and Drug Resistance Among Patients Receiving ART in San Mateo County, California, S. Dalai MSc, S. Sethi MSc, V. Levy MD, D.

Enfuvirtide for Drug-Resistant HIV Infection in North and South America Simon R. Bababeygy.

Mounir Ait-Khaled, The Predictive Quality of Genotype and Phenotype Data on Virological Response to Salvage Therapy in HIV-1 Infected Patients.

Potential Utility of Tipranavir in Current Clinical Practice Daniel R. Kuritzkes, MD Director of AIDS Research Brigham and Woman’s Hospital Division of.

Viral tropism by geno2pheno as a tool for predicting CD4 decrease in HIV-1 infected naïve patients with high CD4 counts Viral tropism by geno2pheno as.

Drug Resistance Reports

HIV-1 Resistance - Implications For Clinicians Joseph J. Eron Jr., MD Professor of Medicine University of North Carolina.

1 Adherence to ARV Therapy and Resistance HAIVN Havard Medical School AIDS Initiative in Vietnam.

Comparison of EFV vs MVC  MERIT Study.  Design N = 361 N = 360  Objective –Non inferiority of MVC vs EFV: % HIV RNA < 400 c/mL and < 50 c/mL (co-primary.

 Design Open-label years Chronic HCV infection Genotype 1 HCV RNA > 10,000 IU/mL HIV co-infection Stable ART* with HIV RNA < 50 c/mL ≥ 24 weeks.

Cumulative plasma HIV-1 level as a novel tool to evaluate antiretroviral therapy efficacy at the individual and public health levels Presented by Viviane.

VIKING Efficacy and safety of dolutegravir in treatment-experienced subjects SE/HIV/0023/14b January 2014.

Herpes Simplex Virus Type 2 infection among U.S. military service members: Public Health Implications and Opportunities for HIV Prevention Christian T.

HIV co-receptor tropism in treatment-naïve patients: impact on CD4 decline and subsequent response to HAART Laura Waters, Sundhiya Mandalia, Adrian Wildfire,

HIV Drug Resistance Surveillance Satellite Session: HIV Drug Resistance Surveillance and Control: a Global Concern Silvia Bertagnolio, MD WHO,

High prevalence of antiretroviral drug resistance among HIV-infected pregnant women in Buenos Aires, Argentina Zapiola 1, D.M. Cecchini 2, S. Fernandez.

Emory University School of Medicine Department of Medicine

Laboratory and clinical data for therapy outcome prediction an overview of presently available tools Francesca Incardona Russian Congress of Laboratory.

RAL + MVC + DRV/r + TDF-FTC

PHOTON-2 Study: SOF + RBV in HCV-HIV co-infection

Geno2pheno[454]: A Web Server for the Prediction of HIV-1 Coreceptor Usage from Next-Generation Sequencing Data Intervirology 2012;55:113–117 - DOI: /

Virological and immunological efficacy of regimen including MVC

Etravirine in Treatment Experienced DUET-2 (TMC125-C216)

Switch from TDF-based to Elvitegravir-Cobicistat-TAF-FTC Study 109

NYSDOH AIDS Institute Quality of Care Program eHIVQUAL

Within-host evolution of X4 HIV-1 in a rare transmission pair revealed by phylogenetic reconstruction of deep-sequence data Anh Q. Le, Jeremy Taylor, Winnie.

Downtown Community Health Centre

Effect of maraviroc on non-R5 tropic HIV-1: refined analysis of subjects from the phase IIb study A M. Surdo, C. Alteri, M.C. Puertas, P. Saccomandi,

SDC 3: Time until virologic suppression and failure

Is Your Patient Engaged in Care

Changes in HIV-1 Co-receptor Tropism for Patients Participating in the Maraviroc MOTIVATE 1 and 2 Clinical Trials E van der Ryst and M Westby Pfizer Global.

Dr. Velephi Okello, Principal Investigator, MaxART Trial

Monique Nijhuis University Medical Center Utrecht, the Netherlands

Jong-Geun Seo, Gun-Hee Lee, Sung-Pa Park

HIV Treatment: What Can You Do to Get and Keep Patients in Care?

Effect of maraviroc on non-R5 tropic HIV-1: refined analysis of subjects from the phase IIb study A M. Surdo, C. Alteri, M.C. Puertas, P. Saccomandi,

Analysis of co‐receptor usage of circulating viral and proviral HIV genome quasispecies by ultra‐deep pyrosequencing in patients who are candidates for.

Jong-Geun Seo, Gun-Hee Lee, Sung-Pa Park

Changes in HIV-1 Co-receptor Tropism for Patients Participating in the Maraviroc MOTIVATE 1 and 2 Clinical Trials E van der Ryst and M Westby Pfizer Global.

Predicted residual activity of rilpivirine in HIV-1 infected patients failing therapy including NNRTIs efavirenz or nevirapine K. Theys, R.J. Camacho,

Next-generation sequencing technology in clinical virology

Chapter 8 Making Sense of Statistical Significance: Effect Size, Decision Errors, and Statistical Power.

PubMed Research Article

Regulatory-Industry Statistics Workshop , 2019

Presentation transcript:

Next Generation Deep Sequencing to Evaluate Viral Tropism in HIV-1 Patients Exposed to Maraviroc Add-On Therapy for 8 Days *Rachel A. McGovern, Art F.Y. Poon, Manuel Leal, Miguel Genebat, Ezequiel Ruiz-Mateos, P. Richard Harrigan Poster #TUPDA0102

Background The Maraviroc Clinical Test (MCT) evaluates virological response following 8 days of exposure to MVC add-on therapy 27 MCT patients were followed longitudinally by 454 sequence analysis Sequences were interpreted by Geno2Pheno coreceptor algorithm (3.5 FPR cutoff); >2% X4 virus was considered non-R5 Analyses were conducted to identify any association between the degree of viral suppression and g2p score R5 X4 Maraviroc X

In those screened non-R5 by genotype MVC inhibited R5 virus, however the overall pVL remained fairly constant as non-R5 virus took over the population within 8 days. B) Screened non-R5 by deep sequencing A) Screened R5 by deep sequencing

Maraviroc exposure in patients with non-R5 virus led to strong selection for virus with an extremely low FPR In Summary patients with non-R5 virus, when exposed to short-term maraviroc add-on therapy, demonstrated a strong selection for X4 variants having extremely low g2P scores (0 ≤ FPR < 2) in as few as 8 days. False Positive Rate Relative Fitness in the Presence of Maraviroc B) Screened non-R5 (3.4% X4) A)