John W. Mellors, MD
Professor, Department of Medicine, Division of Infectious Diseases - School of Medicine and Department of Infectious Diseases and Microbiology - Graduate School of Public Health (Secondary Appointment)
Chief, Division of Infectious Diseases
Director, HIV/AIDS Program, University of Pittsburgh Medical Center
818 Scaife Hall
3550 Terrace Street
Pittsburgh, PA 15261
BA; Dartmouth College; 1975
MD; Dartmouth College; 1978
HIV/AIDS, new antiretrovirals, HIV drug resistance, antiretroviral therapy, HIV reservoirs and their elimination
Dr. Mellors is a tenured Professor of Medicine (primary) and Infectious Diseases and Microbiology (secondary). He is Chief of Infectious Diseases at the University of Pittsburgh, Principal Investigator of the NIH-funded Pittsburgh AIDS Clinical Trials Unit, and Director of the Virology Core Laboratories for the AIDS Clinical Trials Group and the Microbicide Trials Network, two global HIV research networks.
Dr. Mellors’ research is dedicated to preventing, treating and seeking a cure for HIV infection. His work on the Multicenter AIDS Cohort Study provided critical insight into the relation between viremia and HIV disease progression. His research team also played a key role in developing the first long-term effective antiretroviral therapy. His laboratory has focused on HIV resistance to antiretroviral drugs, which is a major obstacle to effective therapy. His laboratory’s work in this area has helped define the genetic and biochemical basis for HIV resistance to nucleoside and non-nucleoside reverse transcriptase inhibitors of HIV-1 reverse transcriptase, and the clinical impact of such resistance. More recent research projects are focusing on preventiing HIV-1 infection through the use of antiretrovirals and quantifying HIV reservoirs in patients on antiretroviral therapy with the long-term goal of eliminating them.
His laboratory consists of 2-3 doctoral students (IDM and MVM), 4-5 research specialists, 1 medical student, and 2 postdoctoral fellows.
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. Science1996; 272:1167-1170
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.
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
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.
Kemp SD, Shi C*, Bloor S, Harrigan PR, Mellors JW, Larder BA. A novel polymorphism at codon 333 of HIV-1 reverse transcriptase can facilitate dual resistance to AZT and 3TC. J Virol 1998; 72:5093-5098.
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.
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 that suppress resistance to 3'-azido-3'-deoxythymidine. Antimicrob Agents Chemother 2000; 44:1783-1788
Hammond JL*, Koontz DL, Bazmi HZ, Beadle JR, Hostetler SE, Kini GD, Aldern KA, Richman DD, Hostetler KY, Mellors JW. Alkylglycerol prodrugs of phosphonoformate are potent in vitro inhibitors of nucleoside resistant HIV-1 and select for resistance mutations that suppress AZT resistance. Antimicrob Agents Chemother 2001; 45:1621-1628.
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
Gulick RM, Meibom A, Havlir D, Eron J, Mosley A, Chodakewitz JA, Issacs R, Gonzalez C, McMahon D, Richman DD, Robertson M, Mellors JW. Six-year follow-up of HIV-1 infected adults in a clinical trial of combination antiretroviral therapy with indinavir, zidovudine, and lamivudine. AIDS 2003: 17:2345-2349.
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
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
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
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; 81:7852-9
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
Clark SA*, Shulman NS, Bosch RJ, Mellors JW. Reverse transcriptase mutations at codons 118, 208, and 215 cause hypersusceptibility of HIV-1 to nonnucleoside reverse transcriptase inhibitors. AIDS 2006; 20: 981-984.
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
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
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
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.
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 Pathog 2007;3(4): e46.
Brehm JH*, Mellors JW, Sluis-Cremer N. Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance. Biochemistry 2008;47(52): 14020-7.
Sluis-Cremer N, Koontz D, Bassit L, Hernandez-Santiago BI, Detorio M, Rapp KL, Amblard F, Bondada L, Grier J, Coats SJ, Schinazi RF, Mellors JW. Anti-human immunodeficiency virus activity, cross-resistance, cytotoxicity, and intracellular pharmacology of the 3'-azido-2',3'-dideoxypurine nucleosides. Antimicrob Agents Chemother 53:3715-3519, 2009.
McMahon D, Jones J, Wiegand A, Gange SJ, Kearney M, Palmer S, McNulty S, Metcalf JA, Acosta E, Rehm C, Coffin JM, Mellors JW, Maldarelli F. Short course raltegravir intensification does not reduce persistent low level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy. Clin Inf Dis 2010;50(6):912-9
Halvas EK, Wiegand A, Boltz VF, Kearney M, Dissley D, Wantman M, Hammer SC, Palmer S, Vaida F, Coffin JM and Mellors JW. Low frequency NNRTI-resistant variants contribute to failure of efavirenz-containing regimens in treatment-experienced patients J Infect Dis; 2010;201(5):672-80