Frank Maldarelli, M.D., Ph.D.

HIV Dynamics and Replication Program
HIV virion image
HIV Dynamics and Replication Program
HIV DRP staff photo September 2019
HIV Dynamics and Replication Program
Melissa Fernandez work-in-progress seminar August 2018
HIV Dynamics and Replication Program
DRP Conference, October 13, 2021
HIV Dynamics and Replication Program
HIV DRP Think Tank Meeting 2017
HIV Dynamics and Replication Program
Sean Patro's poster presentation at CROI 2019
HIV Dynamics and Replication Program
John Coffin and Stephen Hughes participating in This Week in Virology podcast at 2018 Cold Spring Harbor Retroviruses Meeting
HIV Dynamics and Replication Program
Students and postbac fellows in the HIV Dynamics and Replication Program July 2019

Frank Maldarelli, M.D., Ph.D.

Frank  Maldarelli, M.D., Ph.D.
Senior Investigator
Head, Clinical Retrovirology Section

Dr. Maldarelli heads the Clinical Retrovirology Section, which develops and implements clinical protocols to elucidate mechanisms underlying the emergence of HIV drug resistance in vivo, the dynamics of infection under treatment, and the role of resistance mutations in the efficacy and failure of subsequent treatments.  Representing the clinical research arm of the HIV Dynamics and Replication Program (HIV DRP), Dr. Maldarelli is an Attending Physician in the NIH NIAID/CCMD HIV Clinic and has established extensive collaborations between the HIV DRP in Frederick and both the NCI HIV and AIDS Malignancy Branch and the NIAID HIV clinical research program in Bethesda.

Areas of Expertise

1) clinical research, 2) HIV drug resistance, 3) antiretroviral therapy, 4) computational biology, 5) infectious diseases, 6) virology

Clinical Studies of HIV Drug Resistance

The Clinical Retrovirology Section develops and implements clinical protocols to elucidate mechanisms underlying the emergence of HIV drug resistance in vivo, the dynamics of infection under treatment, and the role of resistance mutations in the efficacy and failure of subsequent treatments.

In the first of three projects conducted by the Clinical Retrovirology Section, our goal is to determine the dynamics of viral replication in HIV-infected patients on suppressive antiretroviral therapy (ART). These studies are being extended in clinical trials performed at NIH and elsewhere to determine the levels of viremia when treatment regimens are either simplified or intensified. We are also exploring new strategies to decrease reservoirs of HIV-1 in infected individuals.

In a second research project, we are investigating the genetic structure of HIV populations in infected individuals. We are using the single-genome sequencing technology developed by the Translational Research Section to analyze and understand the accumulation of genetic variation in the gag/pol and env genes of HIV-1 in a number of different patient groups, including chronically infected patients, both naive and on therapy, as well as in primary and early HIV-1 infection. We are complementing existing single-genome sequencing and allele-specific PCR assays with next-generation sequencing and new single-cell assays for cell-associated HIV RNA and DNA. We are determining precise estimates of the roles of population size, genetic drift, selection, and recombination in shaping HIV populations. The goal of this study is to understand the nature of the forces (mutation, selection, drift, recombination) that mold the genetic diversity of virus populations before and after ART is introduced.

The third project is focused on elucidating the mechanisms of persistent viremia in vivo. We are conducting clinical trials of targeted interventions to characterize HIV reservoirs in individuals suppressed on ART. We are determining the role of generalized immune activation and gut-associated lymphoid tissue (GALT) on persistence using nonabsorbable antibiotics to specifically reduce gut bacteria, and studying the effects of specific antigenic activation on HIV using immunization and sampling protocols. We are also investigating the role of target cell number on HIV reservoirs by studying the effects of cytotoxic chemotherapeutics on HIV viremia, and we are investigating the role of innate immunity in HIV persistence by studying the effects of the innate immune modulator interferon alpha 2b.

NIH Scientific Focus Areas:
Clinical Research, Computational Biology, Microbiology and Infectious Diseases, Virology
View Dr. Maldarelli's PubMed Summary.

Selected Key Publications

  1. Patro SC, Brandt LD, Bale MJ, Halvas EK, Joseph KW, Shao W, Wu X, Guo S, Murrell B, Wiegand A, Spindler J, Raley C, Hautman C, Sobolewski M, Fennessey CM, Hu WS, Luke B, Hasson JM, Niyongabo A, Capoferri AA, Keele BF, Milush J, Hoh R, Deeks SG, Maldarelli F, Hughes SH, Coffin JM, Rausch JW, Mellors JW, Kearney MF.
    Proc Natl Acad Sci U S A. 116(51): 25891-99, 2019. [ Journal Article ]
  2. Bozzi G, Simonetti FR, Watters SA, Anderson EM, Gouzoulis M, Kearney MF, Rote P, Lange C, Shao W, Gorelick R, Fullmer B, Kumar S, Wank S, Hewitt S, Kleiner DE, Hattori J, Bale MJ, Hill S, Bell J, Rehm C, Grossman Z, Yarchoan R, Uldrick T, Maldarelli F.
    Sci Adv. 5(9): eaav2045, 2019. [ Journal Article ]
  3. Polizzotto MN, Uldrick TS, Wyvill KM, Aleman K, Peer CJ, Bevans M, Sereti I, Maldarelli F, Whitby D, Marshall V, Goncalves PH, Khetani V, Figg WD, Steinberg SM, Zeldis JB, Yarchoan R.
    J Clin Oncol. 34(34): 4125-31, 2016. [ Journal Article ]
  4. Simonetti FR, Sobolewski MD, Fyne E, Shao W, Spindler J, Hattori J, Anderson EM, Watters SA, Hill S, Wu X, Wells D, Su L, Luke BT, Halvas EK, Besson G, Penrose KJ, Yang Z, Kwan RW, Van Waes C, Uldrick T, Citrin DE, Kovacs J, Polis MA, Rehm CA, Gorelick R, Piatak M, Keele BF, Kearney MF, Coffin JM, Hughes SH, Mellors JW, Maldarelli F
    Proc. Natl. Acad. Sci. USA. 113: 1883-8, 2016. [ Journal Article ]
  5. Maldarelli F, Wu X, Su L, Simonetti FR, Shao W, Hill S, Spindler J, Ferris AL, Mellors JW, Kearney MF, Coffin JM, Hughes SH.
    Science. 345: 179-83, 2014. [ Journal Article ]

Dr. Frank Maldarelli received his Ph.D. from the City University of New York and his M.D. from Mount Sinai School of Medicine. After completing his residency in internal medicine at The Columbia-Presbyterian Hospital, New York, he joined the Laboratory of Molecular Microbiology at the National Institute of Allergy and Infectious Diseases (NIAID) as a Medical Staff Fellow. In 1998, Dr. Maldarelli joined the HIV Drug Resistance Program (HIV DRP, renamed the HIV Dynamics and Replication Program in 2015) in the National Cancer Institute (NCI) as a Staff Clinician and Head of the In Vivo Biology Group, which was later renamed the Clinical Retrovirology Section. In 2012 he was appointed as a Tenure-Track Investigator, and he was promoted to a tenured Senior Investigator position in 2018. Representing the clinical research arm of the HIV DRP, Dr. Maldarelli has established extensive collaborations between the HIV DRP in Frederick and both the NCI HIV and AIDS Malignancy Branch and the NIAID AIDS clinical research program in Bethesda. He is an Attending Physician in the NIAID/CCMD HIV service, the NCI Liaison to the Leidos HIV Molecular Monitoring Core, and a Scientific Committee Member of the International Workshop on HIV Drug Resistance. He recently served on the NIAID Institutional Review Board (as Chair and Vice-Chair), NIH Infectious Disease Advisory Board, Scientific Advisory Committee of the American Federation for AIDS Research, and Review Panel for the Henry M. Jackson Foundation for the Advancement of Military Medicine. He was a faculty member of the International Society of Infectious Diseases HIV Training Program, NIH Infectious Disease Consult Service, and Center for Bio-Medical Communications Infectious Disease Board Review Course and a lecturer in the Washington D.C. community outreach PACT Program. His awards include the NIH Director’s Group Award in 2015, Center for Cancer Research (CCR) Group Award in 2016, and multiple NIH Bench-to-Bedside and Intramural AIDS Targeted Antiviral Program (IATAP) awards. Dr. Maldarelli currently serves on the Editorial Boards of Journal of Virology, AIDS Research and Therapy, and Frontiers in Microbiology.

Name Position
Lindsey Adams Postbaccalaureate Fellow (CRTA)
Matthew Adan Special Volunteer
Zehava Grossman Ph.D. Scientist (Contr)
Shawn Hill M.S., M.B.A. Research Biologist
Kristi Huik Ph.D. Special Volunteer
Chuen-Yen Corey Lau M.D. Associate Research Physician
Erin Madeen Ph.D. Postdoctoral Fellow (Cancer Prevention Fellowship Program)
Thuy Nguyen Ph.D. Postdoctoral Fellow (Visiting)
James Virga Postbaccalaureate Fellow (CRTA)
Mary-Elizabeth Zipparo Postbaccalaureate Fellow (CRTA)
Shiva Ambardar Special Volunteer 2012-2013

Current or Last Known Position:
Undergraduate Student, College of William and Mary, Williamsburg, VA

Elizabeth Anderson, Ph.D. Postdoctoral Fellow, Postbaccalaureate Fellow 2011-2019

Current or Last Known Position:
Postdoctoral Fellow, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

Himanshu Batra, Ph.D. Special Volunteer 2019-2020

Current or Last Known Position:
Postdoctoral Fellow, Catholic University of America, Washington, DC

Jennifer Bell, R.N., B.S., C.C.R.C, Protocol Coordinator 2014-2020

Current or Last Known Position:
Country Coordinator, Marken Clinical Supply Chain, Overland Park, KS

Giorgio Bozzi, M.D. Infectious Disease Fellow 2015-2016

Current or Last Known Position:
Physician, Department of Biomedical and Clinical Sciences, L. Sacco Hospital, University of Milan, Italy

Margaret Caplan, M.D. Special Volunteer 2009

Current or Last Known Position:
Faculty, Division of Infectious Disease, Department of Medicine, Harbor-UCLA Medical Center, University of California, Los Angeles, CA

Karoll Cortez, M.D. Staff Clinician 2009-2010

Current or Last Known Position:
Medical Officer, U.S. Food and Drug Administration, White Oak, MD

Francesca Cossarini, M.D. Infectious Disease Fellow 2008-2010

Current or Last Known Position:
Fellow, Infectious Diseases, Mt. Sinai Hospital, New York, NY

Kristen Danley, M.D. Summer Student 2006

Current or Last Known Position:
Pediatrician, Karabots Pediatric Care Center, West Philadelphia, PA

Sophie Dean Summer Student 2014 and 2015

Current or Last Known Position:
Undergraduate Student, University of Maryland, College Park, MD

Gabriella Diaz, R.N., B.S.N. Study Coordinator 2012-2014

Current or Last Known Position:
Research Nurse Coordinator, WellStar Health System, Cumming, GA

Monica Gouzoulis, B.S. Postbaccalaureate Fellow 2018-2019

Current or Last Known Position:
Molecular Biology Technician, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD

Junko Hattori, Ph.D. Research Fellow 2013-2016

Current or Last Known Position:
Medical Advisor, Merck Sharp & Dohme, Tokyo, Japan

Kristen Kent, B.S. Summer Student 2019

Current or Last Known Position:
Medical Student, Georgetown University School of Medicine, Washington, DC

Daniel Kordella, M.S. Postbaccalaureate Fellow 2012-2013

Current or Last Known Position:
Associate Scientst III, Upstream Process Development, REGENXBIO, Inc., Rockville, MD

Laure Kouyoudjian, P.A.C. Physician Assistant 2015-2016

Current or Last Known Position:
Physician Assistant, Capital Digestive Care, Bethesda, MD

Nicholas Kovacs, Ph.D. Summer Student 2012 and 2013

Current or Last Known Position:
Talent Consultant, Mix Talent, Columbus, OH

Natalie Lindo, B.S. Postbaccalaureate Fellow 2018-2020

Current or Last Known Position:
Scientist I, Cell Biology, Thermo Fisher Scientific, Frederick, MD

Camille Lange, Ph.D. Postdoctoral Fellow 2015-2020

Current or Last Known Position:
Scientific Program Manager, National Institute of Allergy and Infectious Diseases, Bethesda, MD

Charmaine Peters, M.D. Special Volunteer 2014-2015

Current or Last Known Position:
Chief Medical Resident Physician, Department of Medicine, Eisenhower Health Center, Rancho Mirage, CA

Carrie Poethke, D.O. Postbaccalaureate Fellow 2008-2010

Current or Last Known Position:
Osteopathic Physician, Allina Health, Abbott Northwestern Hospital, Minneapolis, MN

Paula Rote, M.D. M.D. Student 2017-2018

Current or Last Known Position:
Resident Physician, University of Minnesota Medical Center, Minneapolis, MN

Francesco Simonetti, M.D. Infectious Disease Fellow 2013-2015

Current or Last Known Position:
Graduate Student, Johns Hopkins Medical Institutions, Baltimore, MD

Rhoda Smith, R.N. Summer Student 2012

Current or Last Known Position:
Registered Professional Nurse, Veterans Health Administration, Richmond, VA

Tiffany Tanzosh, B.S. Postbaccalaureate Fellow 2010-2012

Current or Last Known Position:
COVID-19 Lead Outbreak Surveillance Coordinator, City of Philadelphia – Department of Public Health, Philadelphia, PA

Sarah Watters, Ph.D. Predoctoral Fellow 2014-2016

Current or Last Known Position:
Strategy and Operations Manager, University College London Hospitals, NHS Foundation Trust, London, UK

Eleanor Wilson, M.H.S., M.D. Infectious Disease Fellow 2010-2011

Current or Last Known Position:
Associate Professor, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD

New Investigator Scholarships, Conference on Retroviruses and Opportunistic Infections

Kristi Huik was awarded a New Investigator Scholarship to present her research findings in the 2020 Conference on Retroviruses and Opportunistic Infections (CROI). CROI scholarship awardees in previous years include Elizabeth Anderson and Camille Lange in 2018 and 2017, Sarah Watters in 2015, and Francesco Simonetti in 2014.

2019 Presentation Award in Microbiology, Annual Biomedical Research Conference for Minority Students

Natalie Lindo received a 2019 Presentation Award in Microbiology for presenting her research findings at the Annual Biomedical Research Conference for Minority Students.

Scholarship Award, International Workshop on HIV Drug Resistance and Treatment Strategies

Kristi Huik was awarded a scholarship to attend the 2018 International Workshop on HIV Drug Resistance and Treatment Strategies in Johannesburg, South Africa. She will give an oral presentation on the latest findings of her research project ("Mechanism of Emergence of Resistance of T97A during Dolutegravir Therapy").

Young Scientist Sponsorship, 68th Lindau Nobel Laureate Meeting

Kristi Huik was awarded a full sponsorship by the Estonian Academy of Sciences to participate in the 68th Lindau Nobel Laureate Meeting in June 2018. She received this award based on her outstanding research on the role of host genetic factors in HIV acquisition, HIV drug resistance, and molecular epidemiology of other infections while she was a Ph.D. student at the University of Tartu before joining the Maldarelli lab. The annual Lindau Nobel Laureate Meeting is a prestigious gathering of around 30 Nobel Laureates and 500-600 young scientists — including postdoctoral fellows, Ph.D. students, and undergraduates — who convene to communicate leading issues in physiology and medicine in a forum that includes lectures, panel discussions, poster sessions, master classes, Agora talks, and science walks.

    Travel Awards, HIV DRP Think Tank Meeting

    Elizabeth Anderson received a $1000 travel award from the HIV DRP for one of the two best presentations by NCI fellows at the 2018 HIV DRP Think Tank Meeting. Francesco Simonetti received this Travel Award for his presentation at the 2014 HIV DRP Think Tank Meeting.

      Travel Award, Fall HIV/AIDS & Cancer Virology Think Tank Meeting

      Paula Rote won a $1000 travel award for her outstanding talk at the 2017 Fall HIV/AIDS & Cancer Virology Think Tank Meeting. This annual Think Tank meeting on the NIH-Bethesda campus provides a venue for students, postdoctoral fellows, and staff scientists to present emerging work and hypotheses in the field of cancer virology. The Think Tank travel awards are provided by the Center of Excellence in HIV/AIDS & Cancer Virology, Center for Cancer Research, NCI.

        Diversity Career Development Program, NIH

        Camille Lange graduated from the Diversity Career Development Program (DCDP) at NIH in 2016. DCDP graduates were nominated and selected among a group of talented NIH staff for participation in this program.

          Scholarship Award, 2016 Towards an HIV Cure Symposium and 21st International AIDS Conference (AIDS 2016)

          Elizabeth Anderson was awarded a scholarship to attend the 2016 Towards an HIV Cure Symposium and the 21st International AIDS Conference (AIDS 2016) in Durban, South Africa. She presented the latest findings of her research project ("Intra-patient, full length analysis of HIV gag genetic variation identifies regions of variability") at both meetings.

            2015 NCI Director's Award

            Members of the NCI HIV Integration Sites Analysis (ISA) team received a group award at the NCI Director's Award ceremony in November 2015 "for discoveries on HIV survival during antiretroviral therapy, revealing the importance of integration site and clonal expansion." The ISA group award recipients included Stephen Hughes, Andrea Ferris, Shawn Hill, Mary Kearney, Frank Maldarelli, Wei Shao, and Jonathan Spindler (HIV DRP); Francesco Simonetti (University of Milan); John Coffin (Tufts University); John Mellors (University of Pittsburgh); and David Wells, Ling Su, and Xiaolin Wu (Leidos Biomedical Research, Inc.).

                                                Photo of NCI Integration Sites Analysis Group in Sept 2015

              NIH Postbac Poster Day Award

              Tiffany Tanzosh was honored for presenting one of the best posters on NIH Postbac Poster Day in 2012. Established in 2001, NIH Postbac Poster Day added a judging component in 2011 to highlight the contributions of postbaccalaureate fellows to the NIH Intramural Research Program. Awardees are recognized for having authored posters that score in the top 20% of all posters presented.