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Lisa M. Frenkel, MD

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Lisa M. Frenkel, MD

Infectious Disease

On staff since March 1995

Academic Title: Professor, Pediatrics and Laboratory Medicine

Research Center: Center for Childhood Infections and Prematurity Research

Overview

Board Certification(s)
Pediatric Infectious Diseases
Pediatrics
Medical/Professional School
University of Kansas, Lawrence
Residency
Pediatrics, UCLA School of Medicine, Los Angeles
Clinical Interests

Prevention and treatment of pediatric HIV disease, neonatal herpes simplex virus (HSV) and congenital cytomegalovirus (CMV) infections

Research Description

Our research focuses on practical questions related to the prevention and treatment of HIV-1 infection in infants, children and adults. We are keenly interested in the implementation of interventions to prevent acquisition of HIV by pregnant and breastfeeding women, mother-to-child-transmission in resource-limited communities. Our studies address the mechanisms that cause some adults but not others to shed HIV-1 in their breast milk or from their genital tract that place the infant at risk during birth and breastfeeding. Our projects evaluate the selection and dynamics of drug-resistant HIV-1 mutants during antiretroviral therapy (ART) and as a result of peripartum chemoprophylaxis given to women and infants. We have developed and transferred practical and economical assays for HIV-1 detection in infants, and for monitoring treatment and drug-resistant mutants in research protocols, and aim to implement these more broadly to improve HIV care across communities.

Current projects include collaborative studies with colleagues in India, Kenya, Mozambique, Peru, Thailand, the USA and Zimbabwe.

Lab URL

http://www.seattlechildrens.org/research/childhood-infections-and-prematurity/frenkel-lab

Research Focus Area

Infectious Disease, Virology

Awards and Honors

Award NameAward DescriptionAwarded ByAward Date
Member, (extended x2yr) NIH-NIAID AIDS Research Review Committee (AIDSRRC) 2011 - 2013
Outstanding Mentor Award of 2011, University of WA, Dept Pediatrics 2011
Extraordinary Professor in the Department of Immunology, Faculty of Health Sciences, 2010 - 2012
Russel Haden Medal for medical student research 1978

Publications

Selection of HIV Resistance Associated With Antiretroviral Therapy Initiated Due to Pregnancy and Suspended Postpartum.
Journal of acquired immune deficiency syndromes (1999) , 2011 Nov 1: 241-247
Oral acyclovir suppression and neurodevelopment after neonatal herpes.
The New England journal of medicine , 2011 Oct 6: 1284-92
Postpartum viral load rebound in HIV-1-infected women treated with highly active antiretroviral therapy: AIDS Clinical Trials Group Protocol A5150.
HIV clinical trials , 2011 Jan-Feb: 9-23
Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons.
The Journal of infectious diseases , 2011 Jan 1: 117-21
Antiretroviral treatment for HIV-infected infants exposed to nevirapine.
JAMA : the journal of the American Medical Association , 2010 Dec 15: 2589; author reply 2589-90
Two clusters of HIV-1 infection, rural Idaho, USA, 2008.
Emerging infectious diseases , 2010 Nov: 1807-9
Safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine in HIV-infected children 7 to 12 years old.
Journal of acquired immune deficiency syndromes (1999) , 2010 Oct: 197-204
Genetic analyses of HIV-1 env sequences demonstrate limited compartmentalization in breast milk and suggest viral replication within the breast that increases with mastitis.
Journal of virology , 2010 Oct: 10812-9
Comment on "The origins of sexually transmitted HIV among men who have sex with men".
Science translational medicine , 2010 Sep 22: 50le1; author reply 50lr1
Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America , 2010 May 15: 1397-404
Nevirapine resistance by timing of HIV type 1 infection in infants treated with single-dose nevirapine.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America , 2010 May 15: 1405-14
Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America , 2010 Mar 15: 898-908
Cross-contamination during processing of dried blood spots used for rapid diagnosis of HIV-1 infection of infants is rare and avoidable.
Journal of virological methods , 2010 Feb: 489-91
Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention.
AIDS research and human retroviruses , 2009 Nov: 1099-106
Compartmentalization of HIV-1 within the female genital tract is due to monotypic and low-diversity variants not distinct viral populations.
PloS one , 2009 Sep 22: e7122
Virologic and immunologic correlates with the magnitude of antibody responses to the hepatitis A vaccine in HIV-infected children on highly active antiretroviral treatment.
Journal of acquired immune deficiency syndromes (1999) , 2009 Sep 1: 17-24
Mental health treatment patterns in perinatally HIV-infected youth and controls.
Pediatrics , 2009 Aug: 627-36
Increased detection of HIV-1 drug resistance at time of diagnosis by testing viral DNA with a sensitive assay.
Journal of acquired immune deficiency syndromes (1999) , 2009 Jul 1: 283-9
Monotypic human immunodeficiency virus type 1 genotypes across the uterine cervix and in blood suggest proliferation of cells with provirus.
Journal of virology , 2009 Jun: 6020-8
Increased mutations in Env and Pol suggest greater HIV-1 replication in sputum-derived viruses compared with blood-derived viruses.
AIDS (London, England) , 2009 May 15: 923-8
Early postpartum pharmacokinetics of lopinavir initiated intrapartum in Thai women.
Antimicrobial agents and chemotherapy , 2009 May: 2189-91
Assessment of mitochondrial toxicity by analysis of mitochondrial protein expression in mononuclear cells.
Cytometry. Part B, Clinical cytometry , 2009 May: 181-90
Potential limitation of CCR5 antagonists: drug resistance more often linked to CXCR4-utilizing than to CCR5-utilizing HIV-1.
AIDS (London, England) , 2008 Nov 12: 2393-5
Transmission cluster of multiclass highly drug-resistant HIV-1 among 9 men who have sex with men in Seattle/King County, WA, 2005-2007.
Journal of acquired immune deficiency syndromes (1999) , 2008 Oct 1: 205-11
Diminished human immunodeficiency virus type 1 DNA yield from dried blood spots after storage in a humid incubator at 37 degrees C compared to -20 degrees C.
Journal of clinical microbiology , 2008 Sep: 2945-9
Detection of nonnucleoside reverse-transcriptase inhibitor-resistant HIV-1 after discontinuation of virologically suppressive antiretroviral therapy.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America , 2008 Aug 1: 421-4
Optimization of the oligonucleotide ligation assay, a rapid and inexpensive test for detection of HIV-1 drug resistance mutations, for non-North American variants.
Journal of acquired immune deficiency syndromes (1999) , 2008 Aug 1: 418-27
Cytomegalovirus and Epstein-Barr virus in breast milk are associated with HIV-1 shedding but not with mastitis.
AIDS (London, England) , 2008 Jul 31: 1453-60
Structured treatment interruptions (STIs) in HIV-1 infected pediatric populations increases interferon gamma production and reduces viremia.
Vaccine , 2008 Jun 6: 3086-9
Planned multiple exposures to autologous virus in HIV type 1-infected pediatric populations increases HIV-specific immunity and reduces HIV viremia.
AIDS research and human retroviruses , 2008 Mar: 401-11
Laboratory indicators of mastitis are not associated with elevated HIV-1 DNA loads or predictive of HIV-1 RNA loads in breast milk.
The Journal of infectious diseases , 2007 Aug 15: 570-6
Methods used to examine compartmentalization of viral populations between the genital tract and peripheral blood.
The Journal of infectious diseases , 2007 Aug 1: 493-4; author reply 494-5
Effectiveness of antenatal group HIV voluntary counseling and testing services in rural India.
AIDS education and prevention : official publication of the International Society for AIDS Education , 2007 Jun: 187-97
Polymerase chain reaction diagnosis of primary human herpesvirus-6 infection in the acute care setting.
The Journal of pediatrics , 2006 Oct: 480-5
HIV type 1 zidovudine (ZDV) resistance in blood and uterine cervical secretions of pregnant women.
AIDS research and human retroviruses , 2006 Sep: 870-3
Blinded, multicenter comparison of methods to detect a drug-resistant mutant of human immunodeficiency virus type 1 at low frequency.
Journal of clinical microbiology , 2006 Jul: 2612-4
Density-dependent decay in HIV-1 dynamics.
Journal of acquired immune deficiency syndromes (1999) , 2006 Mar: 266-76
Model for assessment of proficiency of human immunodeficiency virus type 1 sequencing-based genotypic antiretroviral assays.
Journal of clinical microbiology , 2005 Aug: 3963-70
Evidence that low-level viremias during effective highly active antiretroviral therapy result from two processes: expression of archival virus and replication of virus.
Journal of virology , 2005 Aug: 9625-34
Detection and quantification of human immunodeficiency virus type 1 p24 antigen in dried whole blood and plasma on filter paper stored under various conditions.
Journal of clinical microbiology , 2005 Aug: 3901-5
Immune reconstitution after receipt of highly active antiretroviral therapy in children with advanced or progressive HIV disease and complete or partial viral load response.
The Journal of infectious diseases , 2005 Jul 15: 296-302
Challenges in the diagnosis and management of neonatal herpes simplex virus encephalitis.
Pediatrics , 2005 Mar: 795-7
A population-based study of primary human herpesvirus 6 infection.
The New England journal of medicine , 2005 Feb 24: 768-76
Pharmacokinetics and safety of stavudine in HIV-infected pregnant women and their infants: Pediatric AIDS Clinical Trials Group protocol 332.
The Journal of infectious diseases , 2004 Dec 15: 2167-74
Rapid HIV type 1 testing of women presenting in late pregnancy with unknown HIV status in Lima, Peru.
AIDS research and human retroviruses , 2004 Oct: 1046-52
Comparison of oligonucleotide ligation assay and consensus sequencing for detection of drug-resistant mutants of human immunodeficiency virus type 1 in peripheral blood mononuclear cells and plasma.
Journal of clinical microbiology , 2004 Aug: 3670-4
Persistence of human immunodeficiency virus type 1 subtype B DNA in dried-blood samples on FTA filter paper.
Journal of clinical microbiology , 2004 Aug: 3847-9
Maternal toxicity with continuous nevirapine in pregnancy: results from PACTG 1022.
Journal of acquired immune deficiency syndromes (1999) , 2004 Jul 1: 772-6
A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection.
The Journal of infectious diseases , 2004 Jun 1: 1974-82
Understanding HIV-1 drug resistance.
Therapeutic drug monitoring , 2004 Apr: 116-21
Importance and detection of virus reservoirs and compartments of HIV infection.
Current opinion in microbiology , 2003 Aug: 410-6
Effects of CCR5-delta32 and CCR2-64I alleles on disease progression of perinatally HIV-1-infected children: an international meta-analysis.
AIDS (London, England) , 2003 Jul 25: 1631-8
Evolutionary indicators of human immunodeficiency virus type 1 reservoirs and compartments.
Journal of virology , 2003 May: 5540-6
Multiple viral genetic analyses detect low-level human immunodeficiency virus type 1 replication during effective highly active antiretroviral therapy.
Journal of virology , 2003 May: 5721-30
Effect of cessation of zidovudine prophylaxis to reduce vertical transmission on maternal HIV disease progression and survival.
Journal of acquired immune deficiency syndromes (1999) , 2003 Feb 1: 170-81
Human immunodeficiency virus drug susceptibility and resistance testing.
The Pediatric infectious disease journal , 2002 Jul: 681-3
Human immunodeficiency virus drug susceptibility and resistance testing.
The Pediatric infectious disease journal , 2002 Jul: 681-3
Efficacy and toxicity of antiretroviral therapy using 4 or more agents: application of a strategy for antiretroviral management in human immunodeficiency virus-infected children.
Archives of pediatrics & adolescent medicine , 2002 Jun: 568-73
Efficacy and toxicity of antiretroviral therapy using 4 or more agents: application of a strategy for antiretroviral management in human immunodeficiency virus-infected children.
Archives of pediatrics & adolescent medicine , 2002 Jun: 568-73
Rapid and sensitive oligonucleotide ligation assay for detection of mutations in human immunodeficiency virus type 1 associated with high-level resistance to protease inhibitors.
Journal of clinical microbiology , 2002 Apr: 1413-9
Case report: primary human herpesvirus-6 associated with an afebrile seizure in a 3-week-old infant.
Journal of medical virology , 2002 Mar: 384-7
T69D/N pol mutation, human immunodeficiency virus type 1 RNA levels, and syncytium-inducing phenotype are associated with CD4 cell depletion during didanosine therapy.
The Journal of infectious diseases , 2002 Feb 15: 448-55

Presentations

Presentations TitleEventLocationDate
Invited Speaker, XII Congreso de Enfermedades Infecciosas y Tropicales, Lima, Peru 2011
Invited Speaker, HIV Pathogenesis, Prevention and Treatment 2010. Lima, Peru 2010
Invited Speaker, 2nd Canada-Colombia Collaborative Research Wkshp HIV, Cali, Colombia 2010
Invited Speaker, 5th Annual Research Symposium, Seattle Children’s Research Institute 2010
Invited Speaker, NIH US-Japan, HIV Resistance Meeting, Singapore 2010

Research Funding

Grant TitleGrantorAmountAward Date
“HIV-1 evolution in the female genital tract and trafficking in the blood”NIH/NIAID - 1R01AI091550-01A1Jan. 21, 2011 - Jan. 20, 2016
"Immunologic and Virologic Events in Early HIV Infection" (SEAPIP)NIH - 2 P01 AI057005-06A2 (Mullins)July 15, 2010 - June 30, 2015
"Academic Pediatric Infectious Disease"NIH - 5 T32 HD07233-26May 1, 2010 - April 30, 2012
"Quantification and Dynamics of HIV-1 Drug-Resistant Mutants by Pyrosequencing"NIH - 1 R21 AI084688July 1, 2009 - June 30, 2012
“Low-frequency HIV-1 Drug Resistance Mutations in Primary HIV-1 Infection”NIH - 1 R01 AI078802 (Steckler)April 1, 2009 - March 31, 2014
“International and Domestic Pediatric and Maternal HIV Studies Coordinating Center”NIH - NO1-DK-8-0001Dec. 16, 2007 - Nov. 30, 2013
“International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group” NIH - 1 U01 AI068632 July 1, 2006 - May 31, 2013
“Occurrence and Outcome of Dual HIV-1 Infection”NIH - 2 R37 AI047734 (Mullins)July 5, 2005 - March 31, 2015
“Reservoirs of Drug-Resistant HIV-1”NIH - 5 R01 AI058723 March 1, 2005 - Feb. 28, 1912

Primary Office

Seattle Children's Research Institute
C9S - 8 - Infectious Disease
1900 - 9th Ave
Seattle, WA 98101
206-987-2073

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