John W. Mellors, Division Chief

Dr. Mellors

Biography
Selected Publications
Contact Information

Biography

Dr. Mellors is a tenured Professor of Medicine, Pathology, and Infectious Diseases and Microbiology, and Chief of Infectious Diseases at the University of Pittsburgh. He directs both the primary care and clinical research activities in HIV/AIDS at UPMC Health System. He is the Principal Investigator on the Pittsburgh site for the Adult AIDS Clinical Trials Unit. He is also the Co-Director of the Center for Viral Diseases at the University of Pittsburgh.

Under his guidance, the primary care center provides comprehensive HIV care to over 800 HIV-infected individuals. The clinical trials unit at UPMC has conducted pivotal trials of new antiretrovirals, including protease inhibitors, triple drug combinations, and combination protease inhibitors. Dr. Mellors' research as an investigator on the Multicenter AIDS Cohort Study has provided important insight into the relationship between viral load and disease outcome. These findings have had broad implications for research and patient management. Dr. Mellors' laboratory research effort has focused on the problem of HIV resistance to antiretroviral drugs. His work in this area has helped define the genetic and biochemical basis for HIV resistance to nucleoside reverse transcriptase inhibitors (lamivudine, dioxolane guanosine, zidovudine/lamivudine co-resistance), non-nucleoside reverse transcriptase inhibitors (nevirapine, TIBO derivatives, and 6-acyclic pyrimidines), and the pyrophosphate analog, foscarnet. His laboratory has also developed new recombinant retroviral systems to detect and quantify drug resistant HIV.

Dr. Mellors' administrative activities include membership on the Adult AIDS Clinical Trials Group Research Agenda Committee, the Scientific Agenda Steering Committee, the Executive Committee, the Virology Laboratory Committee, the Organizing Committees of the Annual Conference on Human Retroviruses and Related Infections, the International Workshop on HIV Drug Resistance and Combination Therapies, and the International Workshop on Treatment Experienced Patients. He is also a member of the NIH AIDS and Related Research Study Section, the US Public Health Service Panel on Clinical Practices for the Treatment of HIV Infection, and the International AIDS Society-USA Panel on HIV drug resistance.

To see a description of Dr. Mellors' laboratory, please click here.

Selected Publications

  1. Abbas UL, Anderson RM, Mellors JW. Potential Impact of Antiretroviral Chemoprophylaxis on HIV-1 Transmission in Resource-Limited Settings. PLoS ONE 2007 2(9): e875 (online)
  2. Brehm JH, Koontz D, Meteer JD, Pithak V, Sluis-Cremer N, Mellors JW. Selection of Mutations in the Connection and RNase H Domains of Human Immunodeficiency Virus Type 1 Reverse Transcriptase that Increase Resistance to 3'-Azido-3'-Dideoxythymidine. J Virol 2007;81(15):7852-9. Epub 2007
  3. Margolis DM, Mukherjee L, Fletcher CV, Hogg E, Ogata-Arakaki D, Petersen T, Rusin D, Martinez A, Mellors JW for the ACTG 5165 team. The use of beta-D-2,6-diaminopurine dioxolane with or without mycophenylate mofetil in drug-resistant HIV infection. AIDS 2007; 21:2025-2032
  4. Mellors JW, Margolick JB, Phair JP, Rinaldo CR, Detels R, Jacobson LP, Muñoz A. Prognostic value of HIV-1 RNA, CD4 cell count, and CD4 cell slope for progression to AIDS and death in untreated HIV-1 infection. JAMA 2007;297(21):2349-50
  5. Parikh UM, Zelina S, Sluis-Cremer N, Mellors JW. Molecular Mechanisms of Bi-Directional Antagonism between K65R and Thymidine Analog Mutations in HIV-1 Reverse Transcriptase. AIDS 2007;21:1405–1414
  6. Maldarelli F, Palmer S, King MS, Wiegand A, Polis MA, Mican J, Kovacs JA, Davey RT, Rock-Kress D, Dewar R, Liu S, Metcalf JA, Rehm C, brun SC, Hanna GJ, Kempf DJ, Coffin JM, Mellors JW. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathogens 2007; 4: e46 (online)
  7. Sluis-Cremer N, Sheen CW, Zeline S, Torres PSA, Parikh UM, Mellors JW. Molecular mechanism by which K70E in HIV-1 reverse transcriptase confers resistance to nucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother 2007; 51:48-53
  8. McKinnon JE, Arribas JR, Pulido F, Delgado R, Mellors JW. The level of persistent HIV viremia does not increase after successful simplification of maintenance therapy to lopinavir/ritonavir alone. AIDS 2006; 20:2331-5

  9. Benson CA, Vaida F, Havlir DV, Downey GF, Lederman MM, Gulick RM, Glesby MJ, Wantman M, Bixby CJ, Rhinehart AR, Synder S, Wang R, Patel S, Mellors JW. Randomized trial of treatment interruption prior to optimized antiretroviral therapy for persons with drug-resistant HIV: 48 week virologic results of ACTG A5086. J Inf Dis 2006; 194:1309-18
  10. Parikh UM, Barnas DC, Faruki H, Mellors JW. Antagonism between the HIV-1 Reverse-Transcriptase Mutation K65R and Thymidine-Analogue Mutations at the Genomic Level. J Infect Dis 2006 194:651-60
  11. Swindells S, DiRienzo AG, Wilkin T, Fletcher CV, Margolis DM, Thal GD, Godfrey C, Bastow B, Ray MG, Wang H, Coombs RW, McKinnon, J; Mellors, JW for the A5201 Study Team. Regimen simplification to atazanavir/ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression. JAMA 2006;296: 806-814
  12. 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 low frequency drug-resistant HIV variants. J Clin Micro 2006; 44:2612-2614
  13. Parikh UM, Bacheler L, Koontz D, Mellors JW. The K65R mutation in HIV-1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. J Virol 2006; 80: 4971-4977
  14. Abbas UL, Anderson RM, Mellors JW. Potential impact of antiretroviral therapy on HIV-1 transmission and AIDS mortality in resource limited settings. J Acquir Immune Defic Syndr 2006; 41: 632-641

  15. Hammond JL, Parikh UM, Koontz D, Schleuter-Wirtz S, Chu CK, Bazmi HZ, Schinazi RF, Mellors JW. In vitro selection and analysis of human immunodeficiency virus type 1 resistant to derivatives of ß-2’,3’-didehydro-2’.3’-dideoxy-5-fluorocytidine. Antimicrob Agents Chemother 2005; 49:3930-3932
  16. Parikh UM, Koontz DL, Chu CK, Schinazi RF, Mellors JW. In vitro activity of structurally diverse nucleosides analogs against human immunodeficiency virus type 1 encoding the K65R mutation in reverser transcriptase. Antimicrob Agents Chemother 2005; 49:1139-1144
  17. Hammer SM, Vaida FL, Bennett KS, Holohan MK, Sheiner L, Eron JJ, Wheat LJ, Mitsuyasu RT, Sepkowitz K, Valentine FT, Jacobson MA, Rogers M, Karol C, Saah A, Lewis RH, Manion DJ, Brosgart C, DeGruttola V, Mellors JW. Dual versus single protease inhibitor therapy following antiviral treatment failure: A randomized trial. JAMA 2002; 288:169-180
  18. Lyles RH, Munoz A, Yamashita T, Bazmi H, Detels R, Rinaldo CR, Margolick JB, Phair JP, Mellors JW. Natural history of HIV-1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men. J Infect Dis 2000; 181:872-880
  19. Hostetler KY, Hammond JL, Kini GD, Hostetler SE, Beadle JR, Aldern KA, Chou T-C, Richman DD, Mellors JW. In vitro anti-HIV-1 activity of sn-2-substituted 1-O-octadecyl-sn-glycero-3-phosphonoformate analogues and synergy with zidovudine. Antiviral Chemistry and Chemother 2000; 11:213-220

  20. Bazmi HZ, Hammond JL, Cavalcanti SCG, Chu CK, Schinazi RF, Mellors JW. In vitro selection of mutations in HIV-1 reverse transcriptase that decrease susceptibility to (-) b-D-dioxolane-guanosine and suppress resistance to 3’-azido-3’-deoxythymidine. Antimicrob Agents Chemother 2000; 44:1783-1788

  21. DeGruttola V, Dix L, D’Aquila R, Holder D, Phillips A, Ait-Kahled M, Baxter J, Clevenberg, P, Hammer S, Harrigan R, Katzenstein D, Lanier R, Miller M, Para M, Yerly S, Zolopa A, Murray J, Patick A, Miller V, Castillo S, Pedneault L, Mellors JW. The relation between baseline HIV drug resistance and response to antiretroviral therapy: Re-analysis of retrospective and prospective studies using a standardized data analysis plan. Antiviral Therapy 2000; 5:41-48

  22. Shi C, Mellors JW. A recombinant retroviral system for rapid in vivo analysis of HIV-1 susceptibility to reverse transcriptase inhibitors. Antimicrob Agents Chemother 1997; 41:2781-2785

  23. Gulick R, Mellors JW, Havlir D, Eron J, Gonzalez C, McMahon D, Richman D, Valentine F, Jonas L, Deutsch P, Meibohm A, Holder D, Schleif W, Condra J, Emini E, Chodakewitz J. Treatment with a combination of indinavir, zidovudine, and lamivudine in HIV-infected adults with prior antiretroviral use. N Engl J Med 1997; 337:734-739.

  24. Mellors JW, Munoz A, Giorgi JV, Margolick JB, Tassoni CJ, Gupta P, Kingsley LA, Todd JA, Schrager LK, Saah AJ, Detels RR, Phair JP, Rinaldo CR. Plasma viral load and CD4+T-lymphocytes as prognostic markers in HIV-1 infection. Ann Intern Med 1997; 126:946-954

  25. Mellors JW, Rinaldo CR, Gupta P, White RM, Todd JA, Kingsley LA. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science, 1996; 272:1167-1170

Contact Information

Scaife Hall, Suite 818
3550 Terrace Street
Pittsburgh, PA 15261
Telephone: 412-383-7963
Facsimile: 412-383-7982
Email: Mellors@dom.pitt.edu

 



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