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Daniel Robert Kuritzkes, MD
Physician, Brigham and Women's Hospital
Harriet Ryan Albee Professor of Medicine, Harvard Medical School
Chief, Division of Infectious Diseases

Brigham and Women's Hospital
Department of Medicine
Infectious Diseases
75 Francis Street
Boston, MA 02115

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Research Narrative:
  1. Resistance to antiretroviral drugs
    For many HIV-infected patients, the potential benefits of antiretroviral therapy are limited by emergence of drug-resistant virus.  Work in my laboratory is directed towards understanding mechanisms of resistance to novel entry inhibitors,. Using viruses and virus sequences obtained from patients participating in clinical trials, we are also exploring the mechanisms of resistance to novel agents including CCR5 antagonists and integrase inhibitors.  We are also using quantitative allele-specific PCR and other molecular diagnostic tools to quantify drug-resistant variants that are present as minority members of the viral quasispecies in order to characterize the population dynamics of drug-resistant virus in response to changing selective pressures. Better understanding of the virologic, genetic, and biochemical aspects of resistance to these agents will help direct therapy and may lead to better therapeutic strategies in the future. 
  2. Viral fitness
    Considerable attention has been focused recently on the relationship between drug resistance and viral fitness.  The reduced replicative capacity of highly drug-resistant variants of HIV-1 may contribute to the persistent immunological benefits in patients considered to be “failing” antiretroviral therapy.  We are using a novel recombinant marker virus assay developed in my laboratory to determine the fitness of drug-resistant HIV-1 and study the effect of viral fitness in the evolution of antiretroviral drug resistance.  Ongoing and planned future studies include exploring the fitness of different NRTI-resistant mutants, as well as the fitness of mutants resistant to novel entry inhibitors. 
  3. Viral tropism
    Early in the course of disease, most patients infected with HIV-1 harbor virus that uses CCR5 as the co-receptor for virus entry.  In half of patients, CXCR4-using (X4) virus emerges over time, and appears correlated with advancing immune suppression.  Patients with X4 virus are at greater risk of disease progression, but whether X4 viruses are the cause or consequence of disease progression remains unclear.  We are using a variety of techniques, including ultra-deep pyrosequencing and GWAS, to identify factors that drive the emergence of X4 virus. 
  4. AIDS Clinical Trials
    The Partners/Harvard AIDS Clinical Trials Unit is one of the leading contributors to the scientific agenda of the AIDS Clinical Trials Group, an NIH-funded cooperative group of 55 ACTUs in the United States and in resource-limited countries.   Investigators from the Harvard ACTU currently serve as chair or co-chair of several multi-center randomized clinical trials of HIV therapeutics.  As Principal Investigator of the Harvard AIDS Clinical Trials Unit, and Chair of the ACTG,  I am committed to increasing participation of junior investigators in our studies. 

Publications (Pulled from Harvard Catalyst Profiles):

1. Asundi A, Robles Y, Starr T, Landay A, Kinslow J, Ladner J, White L, Plank RM, Melbourne K, Weisholtz D, Bennett M, Pan H, Stern E, Lin A, Kuritzkes DR, Lin NH. Immunological and Neurometabolite Changes Associated With Switch From Efavirenz to an Integrase Inhibitor. J Acquir Immune Defic Syndr. 2019 Aug 15; 81(5):585-593.

2. Li JZ, Segal FP, Bosch RJ, Lalama CM, Roberts-Toler C, Delagreverie H, Getz R, Garcia-Broncano P, Kinslow J, Tressler R, Van Dam CN, Keefer M, Carrington M, Lichterfeld M, Kuritzkes D, Yu XG, Landay A, Sax PE. ART reduces T cell activation and immune exhaustion markers in HIV controllers. Clin Infect Dis. 2019 May 25.

3. Murray BR, Kratka A, Scherr KA, Eyal N, Blumenthal-Barby J, Freedberg KA, Kuritzkes DR, Hammitt JK, Edifor R, Katz MN, Pollak KI, Zikmund-Fisher BJ, Halpern SD, Barks MC, Ubel PA. What risk of death would people take to be cured of HIV and why? A survey of people living with HIV. J Virus Erad. 2019 Apr 01; 5(2):109-115.

4. Julg B, Dee L, Ananworanich J, Barouch DH, Bar K, Caskey M, Colby DJ, Dawson L, Dong KL, Dubé K, Eron J, Frater J, Gandhi RT, Geleziunas R, Goulder P, Hanna GJ, Jefferys R, Johnston R, Kuritzkes D, Li JZ, Likhitwonnawut U, van Lunzen J, Martinez-Picado J, Miller V, Montaner LJ, Nixon DF, Palm D, Pantaleo G, Peay H, Persaud D, Salzwedel J, Salzwedel K, Schacker T, Sheikh V, Søgaard OS, Spudich S, Stephenson K, Sugarman J, Taylor J, Tebas P, Tiemessen CT, Tressler R, Weiss CD, Zheng L, Robb ML, Michael NL, Mellors JW, Deeks SG, Walker BD. Recommendations for analytical antiretroviral treatment interruptions in HIV research trials-report of a consensus meeting. Lancet HIV. 2019 Apr; 6(4):e259-e268.

5. Phillips AN, Venter F, Havlir D, Pozniak A, Kuritzkes D, Wensing A, Lundgren JD, De Luca A, Pillay D, Mellors J, Cambiano V, Bansi-Matharu L, Nakagawa F, Kalua T, Jahn A, Apollo T, Mugurungi O, Clayden P, Gupta RK, Barnabas R, Revill P, Cohn J, Bertagnolio S, Calmy A. Risks and benefits of dolutegravir-based antiretroviral drug regimens in sub-Saharan Africa: a modelling study. Lancet HIV. 2019 Feb; 6(2):e116-e127.

6. Namazi G, Fajnzylber JM, Aga E, Bosch RJ, Acosta EP, Sharaf R, Hartogensis W, Jacobson JM, Connick E, Volberding P, Skiest D, Margolis D, Sneller MC, Little SJ, Gianella S, Smith DM, Kuritzkes DR, Gulick RM, Mellors JW, Mehraj V, Gandhi RT, Mitsuyasu R, Schooley RT, Henry K, Tebas P, Deeks SG, Chun TW, Collier AC, Routy JP, Hecht FM, Walker BD, Li JZ. The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study: Posttreatment Controllers Identified From 14 Clinical Studies. J Infect Dis. 2018 Nov 05; 218(12):1954-1963.

7. Draz MS, Kochehbyoki KM, Vasan A, Battalapalli D, Sreeram A, Kanakasabapathy MK, Kallakuri S, Tsibris A, Kuritzkes DR, Shafiee H. DNA engineered micromotors powered by metal nanoparticles for motion based cellphone diagnostics. Nat Commun. 2018 10 16; 9(1):4282.

8. Sharaf R, Lee GQ, Sun X, Etemad B, Aboukhater LM, Hu Z, Brumme ZL, Aga E, Bosch RJ, Wen Y, Namazi G, Gao C, Acosta EP, Gandhi RT, Jacobson JM, Skiest D, Margolis DM, Mitsuyasu R, Volberding P, Connick E, Kuritzkes DR, Lederman MM, Yu XG, Lichterfeld M, Li JZ. HIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers. J Clin Invest. 2018 Aug 31; 128(9):4074-4085.

9. Kuritzkes DR. Resistance to Dolutegravir-A Chink in the Armor? J Infect Dis. 2018 Jul 24; 218(5):673-675.

10. Hogan LE, Körner C, Hobbs K, Simoneau CR, Thanh C, Gibson EA, Palmer CD, Pandit A, Marty FM, Kuritzkes DR, Jost S, Ritz J, Henrich TJ. NK-cell activation is associated with increased HIV transcriptional activity following allogeneic hematopoietic cell transplantation. Blood Adv. 2018 06 26; 2(12):1412-1416.