Profile

Lisa M. Frenkel, MD

Lisa M. Frenkel, MD

Infectious Disease

On staff since March 1995

Children's Title: Co-Director, Center for Global Infectious Disease Research

Academic Title: Professor, Pediatrics and Laboratory Medicine

Research Center: Center for Global Infectious Disease Research

Professor of Pediatric Infectious Diseases and Laboratory Medicine; Co-Director of Pediatric Infectious Diseases Virology Clinic. Our research focuses on practical questions related to the prevention of HIV-1 infection in infants, mechanisms leading to shedding of virus in breast milk and genital tract of adults, treatment of drug-resistant virus in children and adults, and understanding mechanisms leading to the persistence of HIV infection.

Over the past 20 years, our group has conducted projects in Peru, Thailand, Mozambique, Kenya and South Africa. These studies aimed to better understand the transmission, selection and persistence of drug-resistant viruses and have included collaborations with other UW, national and international investigators. We have developed economical assays with the goal of making testing accessible to resource-poor communities, to improve the management of HIV infection. Currently, our laboratory located within Seattle Childrens Research Institute (SCRI) focuses primarily on three topics and collaborates broadly with other UW, national and international investigators.

1. Persistence of HIV infection: A major research focus of our work has been to understand the mechanisms that allow HIV to persist despite effective ART. Our group documented that among ART-treated individuals with plasma HIV RNA consistently below the limits of detection included a subset that demonstrated viral evolution, implying low-level viral replication, although the vast majority demonstrated no evolution (Frenkel, JVI, 2003). We were the first to note that transient low-level viremias, or "blips," during ART were usually comprised of populations of identical env and pol sequences (Tobin, JVI, 2005), suggesting production of clonal virus. Our subsequent studies revealed that populations of identical viral sequences in PBMC and sputum (rich in pulmonary macrophages) increase over a decade of ART (Wagner, JVI, 2013), suggesting that clonal proliferation of cells with provirus sustains HIV infection during suppressive ART. Recently, we have documented that identical env sequences have identical integration sites, providing strong supportive evidence that HIV persistence is at least in part due to cellular proliferation, and with ongoing suppressive ART, that these proviruses are increasingly integrated into genes controlling immune functions, the cell cycle or cancers suggesting that interference with these genes expression allows the infected cells to proliferate and/or survive (Wagner, Science, 2014; http://www.sciencemag.org/cgi/content/abstract/science.1256304)

Ongoing projects (R01 AI091550 and R01 AI114348) are focused on understanding whether specific HIV integration events lead to the persistence of HIV DNA that is infectious or defective; use in vitro mutagenesis to determine the effects of specific integration events on cellular function; and on whether during acute HIV infection the antigen specificity of HIV-infected cells that would be targeted for cure in individuals who start ART during this time.

2. Systemic inflammation in HIV-infected individuals: Individuals whose viral replication is suppressed by ART continue to have biomarkers indicative of ongoing diffuse inflammation that accelerates atherosclerosis and cardio- and cerebral-vascular events. Given the timing of HIV acquisition by infected children, substantial morbidity could occur from inflammation despite suppressive ART. We hypothesize that ongoing production of viral RNA or proteins drives inflammation, rather than the alternative hypothesis that immune depletion of gut lymphocytes during acute infection allow bacterial translocation.

An ongoing project (funded by SCRI) aims to determine if low-level production of HIV virions or 16sDNA correlate with immune activation and help develop a short interventional trial to diminish inflammation.

3. HIV Resistance to antiretrovirals: Our group has conducted many studies aimed at better understanding the transmission, selection and persistence of drug-resistant viruses. We have developed economical assays with the goal of making testing accessible to resource-poor communities, to improve the management of HIV infection. Currently, we are conducting a randomized-controlled trial of our oligonucleotide ligation assay (OLA) detection of HIV-drug-resistance pre-ART in Kenya. The primary outcome is the rates of ART-associated suppression of viral replication among subjects randomized to testing or standard-of-care. In addition, we will analyze issues related to transfer of technology and will model the cost-effectiveness of the OLA in ART management. Secondly, with UW bioengineers, we are simplifying this OLA to make a simpler and faster assay.

Ongoing projects (R01 AI100037 and R01 AI110375) aim to better understand the role of specific transmitted mutant codons and define the threshold concentration of mutants that result in virologic failure of ART; to convert our PCR-based assay to an isothermal format; optimize Illumina-based sequencing for use as a clinical assay.

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

Over the past 20 years, our group has conducted projects in Peru, Thailand, Mozambique, Kenya and South Africa. These studies aimed to better understand the transmission, selection and persistence of drug-resistant viruses and have included collaborations with other UW, national and international investigators. We have developed economical assays with the goal of making testing accessible to resource-poor communities, to improve the management of HIV infection. Currently, our laboratory located within Seattle Children's Research Institute (SCRI) focuses primarily on three topics and collaborates broadly with other UW, national and international investigators.
1. Persistence of HIV infection: A major research focus of our work has been to understand the mechanisms that allow HIV to persist despite effective ART. Our group documented that among ART-treated individuals with plasma HIV RNA consistently below the limits of detection included a subset that demonstrated viral evolution, implying low-level viral replication, although the vast majority demonstrated no evolution (Frenkel, JVI, 2003). We were the first to note that transient low-level viremias, or "blips," during ART were usually comprised of populations of identical env and pol sequences (Tobin, JVI, 2005), suggesting production of clonal virus. Our subsequent studies revealed that populations of identical viral sequences in PBMC and sputum (rich in pulmonary macrophages) increase over a decade of ART (Wagner, JVI, 2013), suggesting that clonal proliferation of cells with provirus sustains HIV infection during suppressive ART. Recently, we have documented that identical env sequences have identical integration sites, providing strong supportive evidence that HIV persistence is at least in part due to cellular proliferation, and with ongoing suppressive ART, that these proviruses are increasingly integrated into genes controlling immune functions, the cell cycle or cancers suggesting that interference with these genes expression allows the infected cells to proliferate and/or survive (Wagner, Science, 2014; http://www.sciencemag.org/cgi/content/abstract/science.1256304)
Ongoing projects (R01 AI091550 and R01 AI114348) are focused on understanding whether specific HIV integration events lead to the persistence of HIV DNA that is infectious or defective; use in vitro mutagenesis to determine the effects of specific integration events on cellular function; and on whether during acute HIV infection the antigen specificity of HIV-infected cells that would be targeted for cure in individuals who start ART during this time.
2. Systemic inflammation in HIV-infected individuals: Individuals whose viral replication is suppressed by ART continue to have biomarkers indicative of ongoing diffuse inflammation that accelerates atherosclerosis and cardio- and cerebral-vascular events. Given the timing of HIV acquisition by infected children, substantial morbidity could occur from inflammation despite suppressive ART. We hypothesize that ongoing production of viral RNA or proteins drives inflammation, rather than the alternative hypothesis that immune depletion of gut lymphocytes during acute infection allow bacterial translocation.
An ongoing project (funded by SCRI) aims to determine if low-level production of HIV virions or 16sDNA correlate with immune activation and help develop a short interventional trial to diminish inflammation.
3. HIV Resistance to antiretrovirals: Our group has conducted many studies aimed at better understanding the transmission, selection and persistence of drug-resistant viruses. We have developed economical assays with the goal of making testing accessible to resource-poor communities, to improve the management of HIV infection. Currently, we are conducting a randomized-controlled trial of our oligonucleotide ligation assay (OLA) detection of HIV-drug-resistance pre-ART in Kenya. The primary outcome is the rates of ART-associated suppression of viral replication among subjects randomized to testing or standard-of-care. In addition, we will analyze issues related to transfer of technology and will model the cost-effectiveness of the OLA in ART management. Secondly, with UW bioengineers, we are simplifying this OLA to make a simpler and faster assay.
Ongoing projects (R01 AI100037 and R01 AI110375) aim to better understand the role of specific transmitted mutant codons and define the threshold concentration of mutants that result in virologic failure of ART; to convert our PCR-based assay to an isothermal format; optimize Illumina-based sequencing for use as a clinical assay.

Lab URL

http://www.seattlechildrens.org/research/global-infectious-disease-research/frenkel-lab/

Research Focus Area

Infectious Disease, Virology

Awards and Honors

Award Name Award Description Awarded By Award Date
Best Poster of Meeting, International Workshop on HIV & Hepatitis Virus Drug Resistance 2013
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

  • Beck IA, Deng W, Payant R, Hall R, Bumgarner RE, Mullins JI, Frenkel LM
    Validation of an oligonucleotide ligation assay for quantification of human immunodeficiency virus type 1 drug-resistant mutants by use of massively parallel sequencing.
    Journal of clinical microbiology , 2014 July : 52(7)2320-7
  • Mitchell C, Roemer E, Nkwopara E, Robbins B, Cory T, Rue T, Fletcher CV, Frenkel L
    Correlation between Plasma, Intracellular, and Cervical Tissue Levels of Raltegravir at Steady-State Dosing in Healthy Women.
    Antimicrobial agents and chemotherapy , 2014 June : 58(6)3360-3365
  • Stekler JD, McKernan J, Milne R, Tapia KA, Mykhalchenko K, Holte S, Maenza J, Stevens CE, Buskin SE, Mullins JI, Frenkel LM, Collier AC
    Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013.
    Antiviral therapy , 2014 May
  • Mitchell C, Dross S, Beck IA, Micek MA, Frenkel LM
    Low Concentrations of HIV-1 DNA at Birth Delays Diagnosis, Complicating Identification of Infants for Antiretroviral Therapy to Potentially Prevent the Establishment of Viral Reservoirs.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America , 2014 Apr, : 58(8)1190-3
  • Micek MA, Dross S, Blanco AJ, Beck IA, Matunha L, Seidel K, Montoya P, Matediana E, Gantt S, Gloyd S, Frenkel L
    Transmission of Nevirapine-Resistant HIV Type 1 via Breast Milk to Infants After Single-Dose Nevirapine in Beira, Mozambique.
    The Journal of infectious diseases , 2014 Mar.
  • Nachman S, Zheng N, Acosta EP, Teppler H, Homony B, Graham B, Fenton T, Xu X, Wenning L, Spector SA, Frenkel LM, Alvero C, Worrell C, Handelsman E, Wiznia A, International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1066 Study Team
    Pharmacokinetics, safety, and 48-week efficacy of oral raltegravir in HIV-1-infected children aged 2 through 18 years.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America , 2014 Feb. : 58(3)413-22
  • Kantor R, Bettendorf D, Bosch RJ, Mann M, Katzenstein D, Cu-Uvin S, D'Aquila R, Frenkel L, Fiscus S, Coombs R, ACTG A5077 Study Team
    HIV-1 RNA levels and antiretroviral drug resistance in blood and non-blood compartments from HIV-1-infected men and women enrolled in AIDS clinical trials group study A5077.
    PloS one , 2014 : 9(4)e93537
  • Larsen BB, Chen L, Maust BS, Kim M, Zhao H, Deng W, Westfall D, Beck I, Frenkel LM, Mullins JI
    Improved Detection of Rare HIV-1 Variants using 454 Pyrosequencing.
    PloS one , 2013 Oct. : 8(10)e76502
  • Ellis GM, Vlaskin TA, Koth A, Vaz LE, Dross SE, Beck IA, Frenkel LM
    Simultaneous and sensitive detection of human immunodeficiency virus type 1 (HIV) drug resistant genotypes by multiplex oligonucleotide ligation assay.
    Journal of virological methods , 2013 Sept. : 192(1-2)39-43
  • McLaughlin S, Swenson LC, Hu S, Hughes P, Harrigan PR, Coombs RW, Frenkel LM
    Development of a novel codon-specific polymerase chain reaction for the detection of CXCR4-utilizing HIV type 1 subtype B.
    AIDS research and human retroviruses , 2013 May : 29(5)814-25
  • Bull ME, Heath LM, McKernan-Mullin JL, Kraft KM, Acevedo L, Hitti JE, Cohn SE, Tapia KA, Holte SE, Dragavon JA, Coombs RW, Mullins JI, Frenkel LM
    Human immunodeficiency viruses appear compartmentalized to the female genital tract in cross-sectional analyses but genital lineages do not persist over time.
    The Journal of infectious diseases , 2013 Apr, : 207(8)1206-15
  • Ton Q, Frenkel L
    HIV drug resistance in mothers and infants following use of antiretrovirals to prevent mother-to-child transmission.
    Current HIV research , 2013 Mar. : 11(2)126-36
  • Wagner TA, McKernan JL, Tobin NH, Tapia KA, Mullins JI, Frenkel LM
    An increasing proportion of monotypic HIV-1 DNA sequences during antiretroviral treatment suggests proliferation of HIV-infected cells.
    Journal of virology , 2013 Feb. : 87(3)1770-8
  • Mitchell C, Balkus JE, McKernan-Mullin J, Cohn SE, Luque AE, Mwachari C, Cohen CR, Coombs R, Frenkel LM, Hitti J
    Associations between genital tract infections, genital tract inflammation, and cervical cytobrush HIV-1 DNA in US versus Kenyan women.
    Journal of acquired immune deficiency syndromes (1999) , 2013 Feb. : 62(2)143-8
  • Jacobson A, Bell F, Lejarcegui N, Mitchell C, Frenkel L, Horton H
    Healthy Neonates Possess a CD56-Negative NK Cell Population with Reduced Anti-Viral Activity.
    PloS one , 2013 : 8(6)e67700
  • Wagner TA, Lin CH, Tobin NH, Côté HC, Sloan DD, Jerome KR, Frenkel LM
    Quantification of mitochondrial toxicity in HIV-infected individuals by quantitative PCR compared to flow cytometry.
    Cytometry. Part B, Clinical cytometry , 2013 Jan. : 84(1)55-8
  • Mitchell C, Balkus JE, Fredricks D, Liu C, McKernan-Mullin J, Frenkel LM, Mwachari C, Luque A, Cohn SE, Cohen CR, Coombs R, Hitti J
    Interaction between lactobacilli, bacterial vaginosis-associated bacteria, and HIV Type 1 RNA and DNA Genital shedding in U.S. and Kenyan women.
    AIDS research and human retroviruses , 2013 Jan. : 29(1)13-9
  • Jacobson A, Bell F, Lejarcegui N, Mitchell C, Frenkel L, Horton H
    Healthy Neonates Possess a CD56-Negative NK Cell Population with Reduced Anti-Viral Activity.
    PloS one , 2013 : 8(6)e67700
  • Gantt S, Payant R, Carlsson J, Micek MA, Blanco AJ, Beck IA, Matunha L, Montoya P, Matediana E, Gloyd S, Frenkel LM
    Nevirapine-Resistant HIV-1 DNA in Breast Milk After Single-Dose Nevirapine With or Without Zidovudine for Prevention of Mother-to-Child Transmission.
    Journal of the Pediatric Infectious Diseases Society , 2012 Sept. : 1(3)244-249
  • Beck IA, Jang M, McKernan-Mullin J, Bull M, Wagner T, Huang S, Song LY, Nachman S, Krogstad P, Eshleman SH, Wiznia A, Frenkel LM
    Monitoring of HIV type 1 DNA load and drug resistance in peripheral blood mononuclear cells during suppressive antiretroviral therapy does not predict virologic failure.
    AIDS research and human retroviruses , 2012 Aug. : 28(8)780-8
  • Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, Tappero JW, Bukusi EA, Cohen CR, Katabira E, Ronald A, Tumwesigye E, Were E, Fife KH, Kiarie J, Farquhar C, John-Stewart G, Kakia A, Odoyo J, Mucunguzi A, Nakku-Joloba E, Twesigye R, Ngure K, Apaka C, Tamooh H, Gabona F, Mujugira A, Panteleeff D, Thomas KK, Kidoguchi L, Krows M, Revall J, Morrison S, Haugen H, Emmanuel-Ogier M, Ondrejcek L, Coombs RW, Frenkel L, Hendrix C, Bumpus NN, Bangsberg D, Haberer JE, Stevens WS, Lingappa JR, Celum C, Partners PrEP Study Team
    Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.
    The New England journal of medicine , 2012 Aug. : 367(5)399-410
  • Micek MA, Blanco AJ, Carlsson J, Beck IA, Dross S, Matunha L, Seidel K, Montoya P, Gantt S, Matediana E, Jamisse L, Gloyd S, Frenkel LM
    Effects of short-course zidovudine on the selection of nevirapine-resistant HIV-1 in women taking single-dose nevirapine.
    The Journal of infectious diseases , 2012 June : 205(12)1811-5
  • Wagner TA, Frenkel LM
    Yet another reason to treat HIV infection.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America , 2012 Apr, : 54(7)1010-2
  • Soria J, Bull M, Mitchell C, La Rosa A, Dross S, Kraft K, Coombs R, Ticona E, Frenkel L
    Transmitted HIV resistance to first-line antiretroviral therapy in Lima, Peru.
    AIDS research and human retroviruses , 2012 Apr, : 28(4)333-8
  • Cressey TR, Stek A, Capparelli E, Bowonwatanuwong C, Prommas S, Sirivatanapa P, Yuthavisuthi P, Neungton C, Huo Y, Smith E, Best BM, Mirochnick M, IMPAACT P1026s Team
    Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum.
    Journal of acquired immune deficiency syndromes (1999) , 2012 Mar. : 59(3)245-52
  • Siberry GK, Warshaw MG, Williams PL, Spector SA, Decker MD, Jean-Philippe P, Yogev R, Heckman BE, Manzella A, Roa J, Nachman S, Lujan-Zilbermann J, IMPAACT P1065 Protocol Team
    Safety and immunogenicity of quadrivalent meningococcal conjugate vaccine in 2- to 10-year-old human immunodeficiency virus-infected children.
    The Pediatric infectious disease journal , 2012 Jan. : 31(1)47-52
  • Van Dyke RB, Ngo-Giang-Huong N, Shapiro DE, Frenkel L, Britto P, Roongpisuthipong A, Beck IA, Yuthavisuthi P, Prommas S, Puthanakit T, Achalapong J, Chotivanich N, Rasri W, Cressey TR, Maupin R, Mirochnick M, Jourdain G, IMPAACT P1032 Protocol Team
    A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America , 2012 Jan. : 54(2)285-93
  • Ellis GM, Huang S, Hitti J, Frenkel LM, for the P1022 Study Team
    Selection of HIV Resistance Associated With Antiretroviral Therapy Initiated Due to Pregnancy and Suspended Postpartum.
    Journal of acquired immune deficiency syndromes (1999) , 2011 Nov. : 241-247
  • Kimberlin DW, Whitley RJ, Wan W, Powell DA, Storch G, Ahmed A, Palmer A, Sánchez PJ, Jacobs RF, Bradley JS, Robinson JL, Shelton M, Dennehy PH, Leach C, Rathore M, Abughali N, Wright P, Frenkel LM, Brady RC, Van Dyke R, Weiner LB, Guzman-Cottrill J, McCarthy CA, Griffin J, Jester P, Parker M, Lakeman FD, Kuo H, Lee CH, Cloud GA, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group
    Oral acyclovir suppression and neurodevelopment after neonatal herpes.
    The New England journal of medicine , 2011 Oct. : 1284-92
  • Stekler JD, Ellis GM, Carlsson J, Eilers B, Holte S, Maenza J, Stevens CE, Collier AC, Frenkel LM
    Prevalence and impact of minority variant drug resistance mutations in primary HIV-1 infection.
    PloS one , 2011 : 6(12)e28952
  • Sha BE, Tierney C, Cohn SE, Sun X, Coombs RW, Frenkel LM, Kalams SA, Aweeka FT, Bastow B, Bardeguez A, Kmack A, Stek A, Aids Clinical Trials Group ACTG A5150 Team
    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. : 9-23
  • Baeten JM, Lingappa J, Beck I, Frenkel LM, Pepper G, Celum C, Wald A, Fife KH, Were E, Mugo N, Sanchez J, Essex M, Makhema J, Kiarie J, Farquhar C, Corey L
    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. : 117-21
  • Wagner TA, Frenkel LM
    Antiretroviral treatment for HIV-infected infants exposed to nevirapine.
    JAMA : the journal of the American Medical Association , 2010 Dec. : 2589; author reply 2589-90
  • Nett RJ, Bartschi JL, Ellis GM, Hachey DM, Frenkel LM, Roscoe JC, Carter KK, Hahn CG
    Two clusters of HIV-1 infection, rural Idaho, USA, 2008.
    Emerging infectious diseases , 2010 Nov. : 1807-9
  • Levin MJ, Moscicki AB, Song LY, Fenton T, Meyer WA 3rd, Read JS, Handelsman EL, Nowak B, Sattler CA, Saah A, Radley DR, Esser MT, Weinberg A, IMPAACT P1047 Protocol Team
    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
  • Gantt S, Carlsson J, Heath L, Bull ME, Shetty AK, Mutsvangwa J, Musingwini G, Woelk G, Zijenah LS, Katzenstein DA, Mullins JI, Frenkel LM
    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
  • Heath L, Frenkel LM, Foley BT, Mullins JI
    Comment on "The origins of sexually transmitted HIV among men who have sex with men".
    Science translational medicine , 2010 Sept. : 50le1; author reply 50lr1
  • Jourdain G, Wagner TA, Ngo-Giang-Huong N, Sirirungsi W, Klinbuayaem V, Fregonese F, Nantasen I, Techapornroong M, Halue G, Nilmanat A, Wittayapraparat P, Chalermpolprapa V, Pathipvanich P, Yuthavisuthi P, Frenkel LM, Lallemant M
    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 : 1397-404
  • Micek MA, Blanco AJ, Beck IA, Dross S, Matunha L, Montoya P, Seidel K, Gantt S, Matediane E, Jamisse L, Gloyd S, Frenkel LM
    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 : 1405-14
  • Lallemant M, Ngo-Giang-Huong N, Jourdain G, Traisaithit P, Cressey TR, Collins IJ, Jarupanich T, Sukhumanant T, Achalapong J, Sabsanong P, Chotivanich N, Winiyakul N, Ariyadej S, Kanjanasing A, Ratanakosol J, Hemvuttiphan J, Kengsakul K, Wannapira W, Sittipiyasakul V, Pornkitprasarn W, Liampongsabuddhi P, McIntosh K, Van Dyke RB, Frenkel LM, Koetsawang S, Le Coeur S, Kanchana S
    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. : 898-908
  • Mitchell C, Kraft K, Peterson D, Frenkel L
    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
  • Chi BH, Ellis GM, Chintu N, Cantrell RA, Sinkala M, Aldrovandi GM, Warrier R, Mbewe F, Nakamura K, Stringer EM, Frenkel LM, Stringer JS
    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
  • Bull M, Learn G, Genowati I, McKernan J, Hitti J, Lockhart D, Tapia K, Holte S, Dragavon J, Coombs R, Mullins J, Frenkel L
    Compartmentalization of HIV-1 within the female genital tract is due to monotypic and low-diversity variants not distinct viral populations.
    PloS one , 2009 Sept. : e7122
  • Weinberg A, Huang S, Fenton T, Patterson-Bartlett J, Gona P, Read JS, Dankner WM, Nachman S
    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 Sept. : 17-24
  • Chernoff M, Nachman S, Williams P, Brouwers P, Heston J, Hodge J, Di Poalo V, Deygoo NS, Gadow KD, IMPAACT P1055 Study Team
    Mental health treatment patterns in perinatally HIV-infected youth and controls.
    Pediatrics , 2009 Aug. : 627-36
  • Ellis GM, Page LC, Burman BE, Buskin S, Frenkel LM
    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 July : 283-9
  • Bull ME, Learn GH, McElhone S, Hitti J, Lockhart D, Holte S, Dragavon J, Coombs RW, Mullins JI, Frenkel LM
    Monotypic human immunodeficiency virus type 1 genotypes across the uterine cervix and in blood suggest proliferation of cells with provirus.
    Journal of virology , 2009 June : 6020-8
  • Cressey TR, Van Dyke R, Jourdain G, Puthanakit T, Roongpisuthipong A, Achalapong J, Yuthavisuthi P, Prommas S, Chotivanich N, Maupin R, Smith E, Shapiro DE, Mirochnick M, IMPAACT P1032 Team
    Early postpartum pharmacokinetics of lopinavir initiated intrapartum in Thai women.
    Antimicrobial agents and chemotherapy , 2009 May : 2189-91
  • Lin CH, Sloan DD, Dang CH, Wagner T, Cabrera AJ, Tobin NH, Frenkel LM, Jerome KR
    Assessment of mitochondrial toxicity by analysis of mitochondrial protein expression in mononuclear cells.
    Cytometry. Part B, Clinical cytometry , 2009 May : 181-90
  • Wagner TA, Tobin NH, McKernan JL, Xu M, Melvin AJ, Mohan KM, Learn GH, Mullins JI, Frenkel LM
    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 : 923-8
  • Wagner TA, Frenkel LM
    Potential limitation of CCR5 antagonists: drug resistance more often linked to CXCR4-utilizing than to CCR5-utilizing HIV-1.
    AIDS (London, England) , 2008 Nov. : 2393-5
  • Buskin SE, Ellis GM, Pepper GG, Frenkel LM, Pergam SA, Gottlieb GS, Horwitch C, Olliffe JF, Johnson K, Shalit P, Heinen C, Schwartz M, Wood RW
    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. : 205-11
  • Mitchell C, Jennings C, Brambilla D, Aldrovandi G, Amedee AM, Beck I, Bremer JW, Coombs R, Decker D, Fiscus S, Fitzgibbon J, Luzuriaga K, Moye J, Palumbo P, Reichelderfer P, Somasundaran M, Stevens W, Frenkel L, Dried Blood Spot Working Group of the Infant Maternal Pediatric Adolescent AIDS Clinical Trials Network
    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 Sept. : 2945-9
  • Hare CB, Mellors J, Krambrink A, Su Z, Skiest D, Margolis DM, Patel SS, Barnas D, Frenkel L, Coombs RW, Aweeka F, Morse GD, Haas DW, Boltz V, Palmer S, Coffin J, Havlir DV
    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. : 421-4
  • Beck IA, Crowell C, Kittoe R, Bredell H, Machaba M, Willamson C, Janssens W, Jallow S, van der Groen G, Shao Y, Jacob M, Samuel NM, de Rivera IL, Ngo-Giang-Huong N, Cassol S, Alemnji G, Frenkel LM
    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. : 418-27
  • Gantt S, Carlsson J, Shetty AK, Seidel KD, Qin X, Mutsvangwa J, Musingwini G, Woelk G, Zijenah LS, Katzenstein DA, Frenkel LM
    Cytomegalovirus and Epstein-Barr virus in breast milk are associated with HIV-1 shedding but not with mastitis.
    AIDS (London, England) , 2008 July : 1453-60
  • Borkowsky W, Yogev R, Muresan P, McFarland E, Frenkel L, Fenton T, Capparelli E, Moye J, Harding P, Ellis N, Heckman B, Kraimer J
    Structured treatment interruptions (STIs) in HIV-1 infected pediatric populations increases interferon gamma production and reduces viremia.
    Vaccine , 2008 June : 3086-9
  • Borkowsky W, Yogev R, Muresan P, McFarland E, Frenkel L, Fenton T, Capparelli E, Moye J, Harding P, Ellis N, Heckman B, Kraimer J
    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
  • Bull ME, Learn GH, Mullins JI, Frenkel LM
    Methods used to examine compartmentalization of viral populations between the genital tract and peripheral blood.
    The Journal of infectious diseases , 2007 Aug. : 493-4; author reply 494-5
  • Gantt S, Shetty AK, Seidel KD, Matasa K, Musingwini G, Woelk G, Zijenah LS, Katzenstein DA, Frenkel LM
    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. : 570-6
  • Gupta D, Lhewa D, Viswanath R, Jacob SM, Parameshwari S, Radhakrishnan R, Seidel K, Frenkel LM, Samuel NM, Melvin AJ
    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 June : 187-97
  • Zerr DM, Frenkel LM, Huang ML, Rhoads M, Nguy L, Del Beccaro MA, Corey L
    Polymerase chain reaction diagnosis of primary human herpesvirus-6 infection in the acute care setting.
    The Journal of pediatrics , 2006 Oct. : 480-5
  • Frenkel LM, McKernan J, Dinh PV, Goldman D, Hitti J, Watts DH, Cooper ER, Dragavon J, Coombs RW
    HIV type 1 zidovudine (ZDV) resistance in blood and uterine cervical secretions of pregnant women.
    AIDS research and human retroviruses , 2006 Sept. : 870-3
  • Halvas EK, Aldrovandi GM, Balfe P, Beck IA, Boltz VF, Coffin JM, Frenkel LM, Hazelwood JD, Johnson VA, Kearney M, Kovacs A, Kuritzkes DR, Metzner KJ, Nissley DV, Nowicki M, Palmer S, Ziermann R, Zhao RY, Jennings CL, Bremer J, Brambilla D, Mellors JW
    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 July : 2612-4
  • Holte SE, Melvin AJ, Mullins JI, Tobin NH, Frenkel LM
    Density-dependent decay in HIV-1 dynamics.
    Journal of acquired immune deficiency syndromes (1999) , 2006 Mar. : 266-76
  • Huang DD, Bremer JW, Brambilla DJ, Palumbo PE, Aldrovandi G, Eshleman S, Brown C, Fiscus S, Frenkel L, Hamdan H, Hart S, Kovacs A, Krogstad P, LaRussa P, Sullivan J, Weinberg A, Zhao YQ, Pediatric ACTG Sequencing Working Group
    Model for assessment of proficiency of human immunodeficiency virus type 1 sequencing-based genotypic antiretroviral assays.
    Journal of clinical microbiology , 2005 Aug. : 3963-70
  • Tobin NH, Learn GH, Holte SE, Wang Y, Melvin AJ, McKernan JL, Pawluk DM, Mohan KM, Lewis PF, Mullins JI, Frenkel LM
    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
  • Li CC, Seidel KD, Coombs RW, Frenkel LM
    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
  • Kovacs A, Montepiedra G, Carey V, Pahwa S, Weinberg A, Frenkel L, Capparelli E, Mofenson L, Smith E, McIntosh K, Burchett SK, Pediatric AIDS Clinical Trials Group 366 Study Team
    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 July : 296-302
  • Frenkel LM
    Challenges in the diagnosis and management of neonatal herpes simplex virus encephalitis.
    Pediatrics , 2005 Mar. : 795-7
  • Zerr DM, Meier AS, Selke SS, Frenkel LM, Huang ML, Wald A, Rhoads MP, Nguy L, Bornemann R, Morrow RA, Corey L
    A population-based study of primary human herpesvirus 6 infection.
    The New England journal of medicine , 2005 Feb. : 768-76
  • Wade NA, Unadkat JD, Huang S, Shapiro DE, Mathias A, Yasin S, Ciupak G, Watts DH, Delke I, Rathore M, Hitti J, Frenkel L, Samelson R, Smith ME, Mofenson L, Burchett SK
    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. : 2167-74
  • Melvin AJ, Alarcon J, Velasquez C, Rodriguez C, Piscoya J, Giraldo A, Dinh P, Frenkel LM
    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
  • Ellis GM, Mahalanabis M, Beck IA, Pepper G, Wright A, Hamilton S, Holte S, Naugler WE, Pawluk DM, Li CC, Frenkel LM
    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
  • Li CC, Beck IA, Seidel KD, Frenkel LM
    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
  • Hitti J, Frenkel LM, Stek AM, Nachman SA, Baker D, Gonzalez-Garcia A, Provisor A, Thorpe EM, Paul ME, Foca M, Gandia J, Huang S, Wei LJ, Stevens LM, Watts DH, McNamara J
    Maternal toxicity with continuous nevirapine in pregnancy: results from PACTG 1022.
    Journal of acquired immune deficiency syndromes (1999) , 2004 July : 772-6
  • Dybul M, Nies-Kraske E, Dewar R, Maldarelli F, Hallahan CW, Daucher M, Piscitelli SC, Ehler L, Weigand A, Palmer S, Metcalf JA, Davey RT, Rock Kress DM, Powers A, Beck I, Frenkel L, Baseler M, Coffin J, Fauci AS
    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 June : 1974-82
  • Frenkel LM, Tobin NH
    Understanding HIV-1 drug resistance.
    Therapeutic drug monitoring , 2004 Apr, : 116-21
  • Nickle DC, Shriner D, Mittler JE, Frenkel LM, Mullins JI
    Importance and detection of virus reservoirs and compartments of HIV infection.
    Current opinion in microbiology , 2003 Aug. : 410-6
  • Ioannidis JP, Contopoulos-Ioannidis DG, Rosenberg PS, Goedert JJ, De Rossi A, Espanol T, Frenkel L, Mayaux MJ, Newell ML, Pahwa SG, Rousseau C, Scarlatti G, Sei S, Sen L, O'Brien TR, HIV Host Genetics International Meta-Analysis Group
    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 July : 1631-8
  • Nickle DC, Jensen MA, Shriner D, Brodie SJ, Frenkel LM, Mittler JE, Mullins JI
    Evolutionary indicators of human immunodeficiency virus type 1 reservoirs and compartments.
    Journal of virology , 2003 May : 5540-6
  • Frenkel LM, Wang Y, Learn GH, McKernan JL, Ellis GM, Mohan KM, Holte SE, De Vange SM, Pawluk DM, Melvin AJ, Lewis PF, Heath LM, Beck IA, Mahalanabis M, Naugler WE, Tobin NH, Mullins JI
    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
  • Bardeguez AD, Shapiro DE, Mofenson LM, Coombs R, Frenkel LM, Fowler MG, Huang S, Sperling RS, Cunningham B, Gandia J, Maupin R, Zorrilla CD, Jones T, O'Sullivan MJ
    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. : 170-81
  • Tobin NH, Frenkel LM
    Human immunodeficiency virus drug susceptibility and resistance testing.
    The Pediatric infectious disease journal , 2002 July : 681-3
  • Tobin NH, Frenkel LM
    Human immunodeficiency virus drug susceptibility and resistance testing.
    The Pediatric infectious disease journal , 2002 July : 681-3
  • Melvin AJ, Lewis PF, Mohan KM, Naugler WS, Frenkel LM
    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 June : 568-73
  • Melvin AJ, Lewis PF, Mohan KM, Naugler WS, Frenkel LM
    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 June : 568-73
  • Beck IA, Mahalanabis M, Pepper G, Wright A, Hamilton S, Langston E, Frenkel LM
    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
  • Zerr DM, Yeung LC, Obrigewitch RM, Huang ML, Frenkel LM, Corey L
    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
  • Naugler WE, Yong FH, Carey VJ, Dragavon JA, Coombs RW, Frenkel LM
    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. : 448-55

Presentations

Presentations Title Event Location Date
Rapid inexpensive point-of-care assays Global WACh Seminar Series: 2014
Strategies Towards HIV CURE for Infected Children Washington, DC 2013
HIV Reservoirs and Viral Eradication Transformative Science Group 2013
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 Title Grantor Amount Award Date
"Evaluation of mHealth strategies to optimize adherence and efficacy of PMTCT/ART" - R01 HD080460 (PI: John-Stewart) NIH $11,393 subcontract annual direct costs May 1, 2014 - April 30, 2019
"A rapid point-of-treatment diagnostic assay for HIV-resistance to 1st-line ART" - R01 AI110375 NIH $250,000 annual direct costs May 1, 2014 - April 30, 2019
Mechanisms of Formation and Persistence of Active HIV Reservoirs - R01 AI111806 (PI: Mullins) NIH $114,390 subcontract annual direct costs April 1, 2014 - March 31, 2019
"International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group" Virology Lab - UM1 AI106716 (PI: Aldrovandi) NIH $95,547 annual direct costs Jan. 1, 2014 - Nov. 30, 2020
"University of Washington Center for AIDS Research" (CFAR) - P30 AI027757 (PI: Holmes) NIH $95,547 annual direct costs June 1, 2013 - May 31, 2015
"Drug-resistance testing in Kenya to improve ART suppression of HIV replication" (PEPFAR) - R01 AI100037 NIH $695,729 annual direct costs June 3, 2012 - May 31, 2015
"Academic Pediatric Infectious Disease" - T32 HD007233 NIH $277,930 annual direct costs May 1, 2012 - April 30, 2017
"HIV-1 evolution in the female genital tract and trafficking in the blood" - R01AI091550. NIH/NIAID $254,817 annual direct costs Jan. 21, 2011 - Dec. 31, 2015
"Immunologic and Virologic Events in Early HIV Infection" (SEAPIP) - P01 AI057005 (Mullins). NIH $101,000 annual direct costs July 15, 2010 - June 30, 2015
"Low-frequency HIV-1 Drug Resistance Mutations in Primary HIV-1 Infection" - R01 AI078802 (Steckler) NIH $61,594 annual direct costs April 1, 2009 - June 30, 2015
"International and Domestic Pediatric and Maternal HIV Studies Coordinating Center" - NO1-DK-8-0001 (Melvin). NIH $11,360 annual direct costs Dec. 16, 2007 - Nov. 30, 2014
"Occurrence and Outcome of Dual HIV-1 Infection" - R37 AI047734 (Mullins) NIH $4,987 annual direct costs July 5, 2005 - March 31, 2015