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TTV viral load as a marker for immune reconstitution after initiation of HAART in HIV-infected patients

Madsen, Chris D LU ; Eugen-Olsen, Jesper ; Kirk, Ole ; Parner, Jan ; Kaae Christensen, Jens ; Brasholt, Marie S ; Ole Nielsen, Jens and Krogsgaard, Kim (2002) In Clinical Trials 3(4). p.95-287
Abstract

PURPOSE: To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART).

METHOD: Fifteen protease inhibitor-naïve HIV-infected patients were included in a longitudinal study. From each patient, three serum samples taken before HAART initiation and three samples taken during HAART were analyzed. TTV was detected by polymerase chain reaction (PCR) and was quantitated by competitive PCR. TTV viral heterogeneity was determined by restriction fragment length polymorphisms (RFLPs) and sequencing.

RESULTS: All 15 HIV-infected patients were TTV positive. No significant change in HIV RNA or TTV... (More)

PURPOSE: To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART).

METHOD: Fifteen protease inhibitor-naïve HIV-infected patients were included in a longitudinal study. From each patient, three serum samples taken before HAART initiation and three samples taken during HAART were analyzed. TTV was detected by polymerase chain reaction (PCR) and was quantitated by competitive PCR. TTV viral heterogeneity was determined by restriction fragment length polymorphisms (RFLPs) and sequencing.

RESULTS: All 15 HIV-infected patients were TTV positive. No significant change in HIV RNA or TTV viral load was observed at the three time points before HAART initiation. Even though HAART lead to an immediate and significant reduction in HIV RNA (p =.0001), a significant reduction in TTV viral load (p =.0002) was not observed until after 3-5 months of HAART. Four patients did not have an increase in CD4+ T cell count after 1 year of HAART; however, a decrease in TTV viral load was still observed, and three of these patients had a reduction in HIV RNA. RFLPs and sequencing revealed that TTV is represented as a heterogeneous population of virus in HIV-infected patients.

CONCLUSION: This pilot study suggests that HAART leads to improved immunological responses, even in patients who do not have an increase in CD4+ T cell counts. We propose that the change in TTV viral load may be useful in the evaluation of cellular immune response at a functional level in HIV-infected patients who receive HAART.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adult, Antiretroviral Therapy, Highly Active, Base Sequence, Biomarkers, CD4 Lymphocyte Count, DNA, Viral, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Phylogeny, Polymorphism, Restriction Fragment Length, RNA, Viral, Torque teno virus, Viral Load, Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't
in
Clinical Trials
volume
3
issue
4
pages
9 pages
publisher
SAGE Publications
external identifiers
  • pmid:12187502
  • scopus:0035986048
ISSN
1528-4336
DOI
10.1310/hct.2002.3.4.004
language
English
LU publication?
no
id
3e358510-d231-4d34-aadc-ffcc6a0cc501
date added to LUP
2016-12-06 10:20:24
date last changed
2024-04-05 12:01:11
@article{3e358510-d231-4d34-aadc-ffcc6a0cc501,
  abstract     = {{<p>PURPOSE: To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART).</p><p>METHOD: Fifteen protease inhibitor-naïve HIV-infected patients were included in a longitudinal study. From each patient, three serum samples taken before HAART initiation and three samples taken during HAART were analyzed. TTV was detected by polymerase chain reaction (PCR) and was quantitated by competitive PCR. TTV viral heterogeneity was determined by restriction fragment length polymorphisms (RFLPs) and sequencing.</p><p>RESULTS: All 15 HIV-infected patients were TTV positive. No significant change in HIV RNA or TTV viral load was observed at the three time points before HAART initiation. Even though HAART lead to an immediate and significant reduction in HIV RNA (p =.0001), a significant reduction in TTV viral load (p =.0002) was not observed until after 3-5 months of HAART. Four patients did not have an increase in CD4+ T cell count after 1 year of HAART; however, a decrease in TTV viral load was still observed, and three of these patients had a reduction in HIV RNA. RFLPs and sequencing revealed that TTV is represented as a heterogeneous population of virus in HIV-infected patients.</p><p>CONCLUSION: This pilot study suggests that HAART leads to improved immunological responses, even in patients who do not have an increase in CD4+ T cell counts. We propose that the change in TTV viral load may be useful in the evaluation of cellular immune response at a functional level in HIV-infected patients who receive HAART.</p>}},
  author       = {{Madsen, Chris D and Eugen-Olsen, Jesper and Kirk, Ole and Parner, Jan and Kaae Christensen, Jens and Brasholt, Marie S and Ole Nielsen, Jens and Krogsgaard, Kim}},
  issn         = {{1528-4336}},
  keywords     = {{Adult; Antiretroviral Therapy, Highly Active; Base Sequence; Biomarkers; CD4 Lymphocyte Count; DNA, Viral; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Phylogeny; Polymorphism, Restriction Fragment Length; RNA, Viral; Torque teno virus; Viral Load; Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{4}},
  pages        = {{95--287}},
  publisher    = {{SAGE Publications}},
  series       = {{Clinical Trials}},
  title        = {{TTV viral load as a marker for immune reconstitution after initiation of HAART in HIV-infected patients}},
  url          = {{http://dx.doi.org/10.1310/hct.2002.3.4.004}},
  doi          = {{10.1310/hct.2002.3.4.004}},
  volume       = {{3}},
  year         = {{2002}},
}