Dr. Halvas' researches the human immunodeficiency virus type 1 (HIV-1). Specifically, he focuses on the development, validation, and testing of new technologies to detect and quantify major- and low-frequency drug-resistant HIV-1 variants. He monitors HIV-1 drug-resistance and evolution by standard genotyping of patient samples, and he investigates the role of low-frequency HIV-1 drug-resistance variants on clinical outcomes. Dr. Halvas also dissects the mechanisms of HIV-1 pathogenesis, carcinogenesis, and persistence as related to HIV cure strategies.
Early in his career, Dr. Halvas' research dissected the structural determinants important for reverse transcriptase fidelity as well as the development and validation of novel genotypic assays used on clinical samples from HIV-1 infected patients) enrolled in either the AIDS Clinical Trial Group (ACTG) or Microbicides Trials Network (MTN). This work was related to the detection/and quantification of major and minor drug-resistance variants employing standard genotyping, single genome sequencing (SGS), and allele-specific PCR in the context of ART efficacy and mother-to-child transmission. This research was instrumental in determining the predictive value that these major and minor HIV-1 drug-resistant variants have on clinical outcomes.
Currently, Dr. Halvas' research involves investigating the role that clonal expansions of HIV-1 infected cells play in HIV-1 persistence and carcinogenesis. This research is being conducted through the application of SGS to detect cellÂassociated viral DNA and RNA, virus-associated RNA, and full length viral genomes, as well as the recovery of infectious virus, and the capture of integration sites in these HIV-1 infected cells.
Dr. Halvas works closely with the HIV Primary Care Center in the Division of Infectious Diseases at the University of Pittsburgh to determine why some HIV-1 infected patients have intermittently detectable viremia, which is likely related to clonal expansions of HIV-1 infected cells.
As a senior member of John Mellors' laboratory, Dr. Halvas’ educational interests are both instructional and supportive, which include training for medical doctors, fellows, graduate students, and technicians in relation to the numerous assays employed to detect and quantify HIV-1.
- BS, University of Pittsburgh, 1992
- PhD, West Virginia University, 2000
- Postdoctoral, University of Pittsburgh, 2005
Education & Training
Halvas EK, Wiegand A, Boltz VF, Kearney M, Dissley D, Wantman M, Hammer SC, Palmer S, Vaida F, Coffin JM, Mellors JW. Low frequency NNRTI-resistant variants contribute to failure of efavirenz-containing regimens in treatment-experienced patients. Journal of Infectious Diseases. 2010; 201(5): 672-80.
McMahon DK, Zheng L, Hitti J, Chan ES, Halvas EK, Hong F, Kabanda J, Taulo F, Kumarasaamy N, Bonh. Greater suppression of Nevirapine resistance with 21-vs 7-day antiretroviral regimens after intrapartum single-dose Nevirapine for prevention of mother-to-child transmission of HIV. Clinical Infectious Diseases. 2013; 56(7): 1044-51.
Simonetti F, Sobolewski M, Fyne E, Shao W, Spindler J, Hattori J, Anderson E, Watters S, Hill S, Wu X, Wells D, Su L, Luke B, Halvas E, Besson G, Penrose K, Yang Z, Kwan R, Van Waes C, Uldrick T. Clonally Expanded CD4+ T cells can produce infectious HIV-1 in vivo. Proceedings of the National Academy of Sciences of the United States of America. 2016; 113(7): 1883-8.
McManus WR, Bale MJ, Spindler J, Wiegand A, Musick A, Patro SC, Sobolewski MD, Victoria K, Musick VK, Anderson EM, Cyktor JC, Halvas EK, Shao W, Wells D, Wu X, Keele BF, Milush JM, Hoh R, Mellors JW, Hughes SH. HIV-1 in Lymph Nodes is Maintained by Cellular Proliferation During Antiretroviral Therapy. Journal of Clinical Investigation. 2019; 130: 4629-4642.
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 W-H, Luke B, Hasson JM, Niyongabo A, Keele BF. Combined HIV-1 Sequence and Integration Site Analysis Informs Viral Dynamics and Allows Reconstruction of Replicating Viral Ancestors. Proceedings of the National Academy of Sciences of the United States of America. 2019; 116(51): 25891-25899.
Halvas E K, Joseph K W, Brandt L D, Guo S, Sobolewski M D,, Jacobs J L, Tumiotto C, Bui J K, Cyktor JC, Keele BF, Morse GD, Bale MJ, Shao W, Kearney MF, Coffin JC, Rausch JW, Wu X, Hughes SH, Mellors JW. HIV-1 Viremia Not Suppressible by Antiretroviral Therapy Can Originate from Large T-Cell Clones Producing Infectious Virus. Journal of Clinical Investigation. 2020; 130(11): 5847-5857.
Halvas EK, Wiegand A, Boltz VF, Kearney M, Dissley D, Wantman M, Hammer SC, Palmer S, Vaida F, Coffin JM, Mellors JW. Low frequency NNRTI-resistant variants contribute to failure of efavirenz-containing regimens in treatment-experienced patients. JID. 2010; 201(5): 672-80.
Mellors J. W., Guo S., Naqvi A., Brandt L. D., Su L., Sun Z., Joseph K. W., Demirov D., Halvas E. K., Butcher D., Scott B., Hamilton A., Heil M., Karim B., Wu X., Hughes S. H. Insertional Activation of STAT3 and LCK by HIV-1 Proviruses in T Cell Lymphomas. Science Advances. 2020; 130(11): 5847-5857.
Joseph K. W., Halvas E. K., Brandt L. D., Patro S. C., Rausch J. W., Chopra A., Mallal S., Kearney M. F., Coffin J. M., Mellors J. W. Deep Sequencing Analysis of Individual HIV-1 Proviruses Reveals Frequent Asymmetric Long Terminal Repeats. Journal of Virology. 2022
Eshleman S. H., Fogel J. M., Halvas E. K., Piwowar-Manning E., Marzinke M. A., Kofron R., Wang Z., Mellors J., McCauley M., Rinehart A. R., Clair M. S., Adeyeye A., Hinojosa J. C., Cabello R., Middelkoop K., Hanscom B., Cohen M. S., Grinsztejn B., Landovitz R. J., HPTN 083 Study Team. HIV RNA screening reduces integrase strand transfer inhibitor resistance risk in persons receiving long-acting cabotegravir for HIV prevention. The Journal of Infectious Diseases. 2022
Title: Understanding Immune Evasion by HIV-1 Repliclones
Role: Principal Investigator
Funding Agency: National Institute of Allergy & Infectious Diseases
Grant Number: R01 AI165031
Start Year: 2021
End Year: 2026
