Almost all HIV infected persons are infected with herpes simplex viruses (HSV). From 40-95% of HIV positive persons are HSV-2 seropositive. Within the last funding period our studies have indicated that among men who have sex with men, prior HSV-2 infection, infection significantly increases the likelihood of acquiring HIV-1 (R.R. 1.7, P=.04). Conversely, among HIV and HSV-2 co-infected persons, high titers of HIV-1 RNA are found in almost all genital lesions for a prolonged duration, suggesting HSV-2 may play an important role in increasing the efficiency of transmission of HIV-1. In addition, frequent subclinical HSV-2 reactivation may be a significant co- factor in initiating bursts of HIV-1 replication in genitourinary compartments and the total HIV-1 viral load. Our proposed studies are centered upon answering these issues. They include: 1) Collaborating with NIAID supported HIVNET to evaluate whether prior HSV-2 infection increases the risk of HIV-1 acquisition in women; 2) Conducting a series of studies to evaluate in subclinical HSV shedding causes HIV-1 replication in semen, cervicovaginal and rectal mucosa; 3) evaluating if antiviral therapy for HSV can suppress HIV replication in genital lesions; 4) Determining if chronic daily acyclovir therapy reduces plasma virus load. HSV infection also affords a unique opportunity for evaluating whether highly active anti-retroviral therapy (HAART) effectively influences host immune control of an opportunistic pathogen. Proposed studies evaluate the frequency of HSV reactivation by quantitative PCR prior to, 4 months after, and 12 months after initiation of HAART in HIV+ persons with high and lower CD4 T cell counts. The above studies will define what management strategies can reduce the morbidity of HSV infection on HIV progression. They will also provide important information on the potential role HSV has in the spread of sexually transmitted and sexually acquired HIV and define potential intervention strategies for interrupting such transmission.

Project Start
2001-04-01
Project End
2002-03-31
Budget Start
Budget End
Support Year
11
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
Schiffer, Joshua T; Swan, Dave A; Roychoudhury, Pavitra et al. (2018) A Fixed Spatial Structure of CD8+ T Cells in Tissue during Chronic HSV-2 Infection. J Immunol 201:1522-1535
Traidl, Stephan; Kienlin, Petra; Begemann, Gabriele et al. (2018) Patients with atopic dermatitis and history of eczema herpeticum elicit herpes simplex virus-specific type 2 immune responses. J Allergy Clin Immunol 141:1144-1147.e5
Ramchandani, Meena; Selke, Stacy; Magaret, Amalia et al. (2018) Prospective cohort study showing persistent HSV-2 shedding in women with genital herpes 2 years after acquisition. Sex Transm Infect 94:568-570
Boucoiran, Isabelle; Mayer, Bryan T; Krantz, Elizabeth M et al. (2018) Nonprimary Maternal Cytomegalovirus Infection After Viral Shedding in Infants. Pediatr Infect Dis J 37:627-631
Kleinstein, Sarah E; Shea, Patrick R; Allen, Andrew S et al. (2018) Genome-wide association study (GWAS) of human host factors influencing viral severity of herpes simplex virus type 2 (HSV-2). Genes Immun :
Gilbert, Peter B; Excler, Jean-Louis; Tomaras, Georgia D et al. (2017) Antibody to HSV gD peptide induced by vaccination does not protect against HSV-2 infection in HSV-2 seronegative women. PLoS One 12:e0176428
Celum, Connie; Hong, Ting; Cent, Anne et al. (2017) Herpes Simplex Virus Type 2 Acquisition Among HIV-1-Infected Adults Treated With Tenofovir Disoproxyl Fumarate as Part of Combination Antiretroviral Therapy: Results From the ACTG A5175 PEARLS Study. J Infect Dis 215:907-910
Abana, Chike O; Pilkinton, Mark A; Gaudieri, Silvana et al. (2017) Cytomegalovirus (CMV) Epitope-Specific CD4+ T Cells Are Inflated in HIV+ CMV+ Subjects. J Immunol 199:3187-3201
Johnston, Christine; Magaret, Amalia; Roychoudhury, Pavitra et al. (2017) Highly conserved intragenic HSV-2 sequences: Results from next-generation sequencing of HSV-2 UL and US regions from genital swabs collected from 3 continents. Virology 510:90-98
Agyemang, Elfriede; Le, Quynh-An; Warren, Terri et al. (2017) Performance of Commercial Enzyme-Linked Immunoassays for Diagnosis of Herpes Simplex Virus-1 and Herpes Simplex Virus-2 Infection in a Clinical Setting. Sex Transm Dis 44:763-767

Showing the most recent 10 out of 345 publications