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Role of GBV-C and human herpes virus coinfections in AIDS development in HIV-1 seroconverters

Shen, Chengli (2014) Role of GBV-C and human herpes virus coinfections in AIDS development in HIV-1 seroconverters. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Background: GB virus type C (GBV-C) co-infection prolongs survival among Human Immunodeficiency Virus (HIV) infected individuals. Chronic immune activation is associated with HIV-1 disease progression.
Objective: To investigate the effect of GBV-C coinfection and herpes virus reactivation on AIDS development in HIV-1 seroconverters.
Methods: A total of 272 men HIV-1 seroconverters were included for the analysis. Cox proportional hazards (PH) regression models were employed to evaluate the effects of GBV-C and herpes viruses (CMV, EBV, HHV6, HHV8) on time from HIV-1 seroconversion to AIDS development. In addition, Gray’s piecewise constant time-varying coefficient (PC-TVC) model that accounts for varying covariate effects over time was employed to estimate the effects for the variables that did not follow PH assumption.
Results: In Cox PH model analysis, GBV-C coinfection delayed AIDS development statistically significant in HIV-1 seroconverters. The log10 GBV-C RNA increase was associated with a 15% decrease in AIDS development, while the high HHV8 and CMV reactivation increased AIDS development respectively. The effects of HHV6 and EBV on AIDS development were not statistically significant. Using Gray PC-TVC model, GBV-C coinfection was associated with delaying AIDS development, especially starting from year 3 of HIV-1 infection, then the hazard ratios decreased over time until 10 years, and kept in low level after 10 years of infection. HHV8 reactivation increased the chance of AIDS development, especially after 3 years of HIV-1 infection. The effect of CMV reactivation was constant with a hazard ratio of 1.38. In addition, two variables, age and baseline CD4+ T cell counts, which were not statistically significant in Cox PH regression model analysis, were statistically significant in Gray PC-TVC model. Similar to Cox PH analysis, the effects of HHV6 and EBV were not statistically significant either on AIDS development.
Conclusion: GBV-C co-infection delayed HIV-1 disease progression. HHV8 and CMV accelerated AIDS development. The effects of HHV6 and EBV were not statistically significant on AIDS development.
Public health importance: This study has important implications for investigating viral coinfections on AIDS development and providing alternative ideas to delay HIV disease progression.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Shen, Chenglichs97@pitt.eduCHS97
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee Chair Marsh, Garygmarsh@pitt.eduGMARSH
Committee MemberChang, Chung-Chou H.changj@pitt.eduCHANGJ
Committee MemberChen, Yuecheny@pitt.eduCHENY
Committee MemberRinaldo, Charles R.rinaldo@pitt.eduRINALDO
Date: 29 September 2014
Date Type: Publication
Defense Date: 21 August 2014
Approval Date: 29 September 2014
Submission Date: 29 August 2014
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 43
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Biostatistics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: GBV-C Herpes Viruses, HIV-1, AIDS
Date Deposited: 30 Sep 2014 00:19
Last Modified: 15 Nov 2016 14:23
URI: http://d-scholarship.pitt.edu/id/eprint/22862

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