HIV infection follows an extremely variable course, with some individuals staying healthy for more than 15 years while others may become ill and die in fewer than five years. Overall, about one of every five HIV positive people is healthy with no symptoms of HIV after 10 years of infection. A small percentage of HIV positive people have identifiable genetic or virus-related factors identified that may explain the slow (or fast) progression of HIV disease; however, these disease-modifying factors are not common and thus do not explain most of the variability in HIV disease. GB Virus type C (GBV-C) is a human virus that was discovered in 1995. It rapidly became clear that the virus is very common in healthy people. Although GBVC persists in about one in every two to three people infected, extensive studies failed to demonstrate an association with any illness. GBV-C grows in CD4+ T lymphocytes, the same cell that HIV grows in. A number of studies found that HIV-positive people have a very high rate of active (39%) or prior (46%) infection with GBV-C, and furthermore, that HIV-positive people who are co-infected with GBV-C appear to live longer than HIV-positive patients without GBV-C infection. Recently, the Multicenter AIDS Cohort Study group (MACS) tested the best-characterized group of HIV-positive patients in the world, and confirmed that GBV-C infection was associated with prolonged survival, confirmed. In addition, the MACS study found that about 20% of the GBV-C and HIV co-infected individuals lost evidence of GBV-C infection during follow up. Individuals who """"""""lost"""""""" the GB virus were almost 6 times more likely to die than those who continued to have active GBV-C infection. We propose to study three large, multicenter cohorts to try to determine why some people lose GBV-C infection. In addition, we will study the association between GBV-C and improved survival in different gender, racial, and ethnic groups. Finally, we will perform exploratory studies designed to identify how GBV-C may improve survival in HIV-positive people. We suspect that it is due to an anti-HIV effect and/or an effect on the host immune system that offers some protection against HIV disease. Determining if this virus is related to delayed HIV disease progression in different groups of people, and understanding how the GB virus slows HIV disease may lead to new approaches to the management of HIV infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI058740-04
Application #
7162933
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Roe, Joanad'Arc C
Project Start
2004-01-01
Project End
2008-12-31
Budget Start
2007-01-01
Budget End
2007-12-31
Support Year
4
Fiscal Year
2007
Total Cost
$610,851
Indirect Cost
Name
University of Iowa
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Martin, Maureen P; Naranbhai, Vivek; Shea, Patrick R et al. (2018) Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1. J Clin Invest 128:1903-1912
Haas, David W; Bradford, Yuki; Verma, Anurag et al. (2018) Brain neurotransmitter transporter/receptor genomics and efavirenz central nervous system adverse events. Pharmacogenet Genomics 28:179-187
Venuto, Charles S; Lim, Jihoon; Messing, Susan et al. (2018) Inflammation investigated as a source of pharmacokinetic variability of atazanavir in AIDS Clinical Trials Group protocol A5224s. Antivir Ther 23:345-351
Li, Binglan; Verma, Shefali S; Veturi, Yogasudha C et al. (2018) Evaluation of PrediXcan for prioritizing GWAS associations and predicting gene expression. Pac Symp Biocomput 23:448-459
Siewe, Basile; Nipper, Allison J; Sohn, Haewon et al. (2017) FcRL4 Expression Identifies a Pro-inflammatory B Cell Subset in Viremic HIV-Infected Subjects. Front Immunol 8:1339
Verma, Anurag; Bradford, Yuki; Verma, Shefali S et al. (2017) Multiphenotype association study of patients randomized to initiate antiretroviral regimens in AIDS Clinical Trials Group protocol A5202. Pharmacogenet Genomics 27:101-111
Bednasz, Cindy J; Venuto, Charles S; Ma, Qing et al. (2017) Efavirenz Therapeutic Range in HIV-1 Treatment-Naive Participants. Ther Drug Monit 39:596-603
Verma, Shefali S; Frase, Alex T; Verma, Anurag et al. (2016) PHENOME-WIDE INTERACTION STUDY (PheWIS) IN AIDS CLINICAL TRIALS GROUP DATA (ACTG). Pac Symp Biocomput 21:57-68
Moore, Carrie B; Verma, Anurag; Pendergrass, Sarah et al. (2015) Phenome-wide Association Study Relating Pretreatment Laboratory Parameters With Human Genetic Variants in AIDS Clinical Trials Group Protocols. Open Forum Infect Dis 2:ofu113
Lehmann, David S; Ribaudo, Heather J; Daar, Eric S et al. (2015) Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols. Pharmacogenet Genomics 25:51-9

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