Goal and Objectives:

The Virology Committee provides scientific expertise in identifying important virologic issues and solving problems through the design of laboratory protocols, as well as (when necessary) clinical protocols. The Virology Committee is essential to the RACs in helping to answer questions relating to HIV pathogenesis in HIV-infected pregnant women, children, and adolescents. It also oversees the Virology core laboratories and assures, through a quality-control program and prioritization of activities, that they function to serve the needs of the PACTG.

The following are the specific aims of the Virology Scientific Committee:                                                                                                                     

Specific Aim 1. To provide and administrate a network of laboratories capable of supplying virologic support to clinical trials protocols, and data that will contribute to a better understanding of the pathogenesis of HIV infection among pregnant women, children, and adolescents.

Specific Aim 2. To provide the capacity for developing and applying new virologic methods and altering existing methods to further the aims of the pediatric scientific agenda.

Specific Aim 3. To provide virologic support and leadership to the RACs and expert virologic advice for the design and execution of clinical trials.

Roster:

Virologic Sub-study of PACTG345 

 Protocol Title: A Phase I/II Study of Ritonavir Therapy in HIV-1 Infected Infants and Children Abst. 467.

PACTG1012 

A Phase I Pharmacokinetic Study of Once Versus Twice Daily Dosing With Zidovudine

Sponsored by: The National Institute of Allergy and Infectious Diseases ; Pharmaceutical Support Provided by: Glaxo Wellcome, Inc.

Roster

Objectives:

Primary

1. Compare the steady state predose amounts of ZDV-triphosphate (TP) and 3TC-TP in is administered once versus twice daily.

2. Describe the kinetics of phosphorylation of ZDV and 3TC mono-, di-, and triphosphates in

Secondary

1. Determine adherence using the PACTG Adherence Modules.

2. Monitor plasma HIV-1 RNA viral load changes on once versus twice daily dosing regimens with Combivir.

3. Provide an estimate of the variability in the expression of MRP4 protein and examine

PACTG1038

ABILITY OF High DOSE  LOPINAVIR/RITONAVIR (KALETRA^TM)  TO ACHIEVE INHIBITORY QUOTIENT ≥15 IN PEDIATRIC SUBJECTS PREVIOUSLY TREATED WITH PROTEASE INHIBITORS

A Multicenter Center Trial of the Pediatric AIDS Clinical Trials Group

Sponsored by: The National Institute of Allergy and Infectious Diseases

Pharmaceutical Support Provided by: Abbott Laboratories

Primary Objectives:  

1.      To measure the proportion of PI-experienced subjects achieving the target IQ on Kaletra alone.

2.     To determine the safety and tolerability of KaletraTM given in higher doses than currently recommended by its manufacturer's information package.

Secondary Objectives:  

1.      To correlate viral genotypes (drug resistance profiles of RT and protease genes) with potential failure in achieving IQ>15, before and after Kaletra^TM treatment.

2.      To compare HIV-1 genotyping with phenotyping assays in their ability to predict susceptibility of the subjects viral isolate to drug treatment.

3.      To estimate pharmacokinetic parameters for Kaletra^TM in protease inhibitor pre-treated HIV-infected children and adolescents receiving doses high enough to achieve concentrations sufficient to provide activity relative to an estimated EC50.

4.      To assess relationship between subject characteristics including age, body size, and gender and Kaletra^TM pharmacokinetic parameters.

5.      To determine variability in systemic exposure over the duration of therapy by measuring pre-dose Kaletra^TM concentrations at regular intervals.

6.      To evaluate genotypes for CYP3A and pGP as contributing sources of variability to Kaletra^TM metabolism.

7.      To determine the free concentrations of lopinavir with concurrent measurements of AAGP and serum albumin.

Team Roster  

AACTG Genotypic Resistance/Sequencing Swat Team Members (1995-1998)

Lisa DeMeter, MD, (Rochester University), Chair
Max Arens, MD (Washington University)
Richard D'Aquila, MD (Harvard University)
Alejo Erice, MD (University of Minnesota)
Joe Fitzgibbon
Tony Japour, MD (Harvard University)
Victoria Johnson, MD (University of Alabama)
Dan Kuritzkes, MD (MIT)
Doug Mayers, MD (Walter Reed Army Institute)
Suraiya Rasheed, MD (USC)
Pat Reichelderfer, PhD (NIH) Originator
Doug Richman, MD (UCSD)
Bob Shafer, MD, (Stanford University)
Owen Weislow, PhD (SRA Technologies Inc.)
Mark WintersYuqi Zhao, PhD, (Northwestern University)

Publications
Demeter, LM, E Fisher, R D'Aquila, O Weislow, A Erice, J Eitzgibbon, R Shafer, D Richman, T Howard, Y Zhao, D Huang, D Mayers, S Sylvester, M Arens, K Sannerud, S Rasheed, V Johnson, D Kuritzkes, P Reichelderfer and A Japour. 1998. Interlaboratory Concordance of DNA Sequence Analysis to Detect Drug Resistance Mutations in HIV-1 Reverse Transcriptase. Journal of Virologic Methods. 75:93-104.

DeMeter, L, D Huang, R Shafer, T Howard, R Schuurman, C White, D Gallahan, O Weislow, R Colgrove, E Fisher, M Arens, Y Zhao, S Rasheed, P Reichelderfer and L Johnston-Dow. 1997. Development of a consensus sequencing protocol to detect drug resistance mutations in HIV-1 protease and reverse transcriptase. 1997 Conference of Infectious Diseases Society of America (IDSA), San Francisco, CA

.DeMeter, L, K. Sannerud, D. Mayers, J. Fitzgibbon, S. Sylvester, M. Arens, E. Fisher, R. Shafer, Y. Zhao, D. Huang, P. Reichelderfer, V. Johnson, D. Richman, S. Rasheed, D. Kuritzkes , A. Japour, and the ACTG Genotypic Resistance Working Group 1995. Interlaboratory concordance of DNA sequence analysis of the HIV?1 reverse transcriptase (RT). Abst. in 35th ICAAC, San Francisco, CA I284, p256.

DeMeter, L, K Sannerud, D Mayers, J Fitzgibbon, S Sylvester, M Arens, E Fisher, R Shafer, Y Zhao, D Huang, P Reichelderfer, V Johnson, D Richman, S Rasheed, D Kuritzkes, A Japour, and the ACTG Genotypic Resistance Working Group 1995. Interlaboratory concordance of DNA sequence analysis of the HIV?1 reverse transcriptase (RT). 20th ACTG Meeting, Washington D.C., #12

In situ Drug Resistance Screening Swat Team Members (1996)

Vinayaka Prasad, MD (Albert Einstein College of Medicine), Chair
Charles Boucher, MD (University of Amsterdam)
Vera Byrnes (Merck Co.)
Pam Chatis (DuPont Col)
Lisa DeMeter, MD (Rochester University)
Lisa Frenkel, MD (University of Washington, Seattle)
Diana Huang, PhD (Rush Medical College, Chicago)
Tony Japour, MD (Beth Israel Hospital)
Israel Lowy, MD (Columbia University)
Doug Mayers, MD (Walter Reed Army Institute)
Yaffa Mizrachi, MD (Albert Einstein College of Medicine)
Suraiya Rasheed, MD (USC)
Robert Shafer, MD (Stanford University)
Ranga Srinivas, MD (St. Jude Children's Hospital)
Kathleen Stellrecht, MD (Albany Medical College)
Yuqi Zhao, PhD (Northwestern University)

ACTG Junior Investigator, Ad Hoc Steering Committee (1995-1998)

Judith Currier, MD (USC)
Carl Fichtenbaum, MD (Washington University, St. Louis)
Trip Gulick, MD (NYU)Stephen Hausrath, MD (Harvard University)
Tony Japour, MD (Harvard University)
Patricia Meehen, PhD (SDAC/FS&T Research Foundation, Inc.)
Stacy Bradley (NIH ACTG Operation Office)
Pat Reichelderfer PhD (NIH DAIDS)
Camlin Tierney, PhD (SDAC/Harvard University)
Yuqi Zhao, PhD (Northwestern University)

HIV-1 Proviral DNA Quantification Working Group (1999 - present)