Abstract
Objective: The objective of this study was to assess the effects of HAART initiation on CD4 T-cell repopulation and T-cell immune activation in rectal and duodenal mucosa. Design: The effects of HAART on the gastrointestinal tract remain controversial, and studies have reached different conclusions regarding its effectiveness at restoring mucosal CD4 T cells depending upon time of initiation, duration of treatment and gastrointestinal tract region studied. Methods: We obtained blood, rectal biopsies and duodenal biopsies from 14 chronically infected individuals at baseline and at 4-9 months post-HAART initiation. We examined CD4 T-cell frequencies in blood, rectum and duodenum at both time points, and performed a detailed assessment of CD4 T-cell phenotype, immune activation marker expression and HIV-specific CD8 T-cell responses in blood and rectal mucosa. Results: CD4 T-cell percentages increased significantly in blood, rectal and duodenal mucosa after 4-9 months of HAART (P1/40.02, 0.0005, 0.0002), but remained lower than in uninfected controls. HIV-specific CD8 T-cell responses in blood and rectal mucosa declined following HAART initiation (P1/40.0015, 0.021). CD8 T-cell coexpression of CD38 and HLA-DR in blood and mucosa, as well as plasma sCD14, declined significantly. CD28 expression on blood and mucosal CD8 T cells increased, whereas programmed death receptor-1 expression on blood HIV-specific CD4 and CD8 T cells decreased. Conclusion: Within the first months of HAART, limited CD4 T-cell reconstitution occurs in small and large intestinal mucosa. Nevertheless, decreased immune activation and increased CD28 expression suggest rapid immunological benefits of HAART despite incomplete CD4 T-cell reconstitution.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 867-877 |
| Number of pages | 11 |
| Journal | AIDS |
| Volume | 27 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 27 2013 |
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Keywords
- Gut
- HAART
- HIV
- Immune activation
- Mucosa
- T cells
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases
Cite this
Impact of highly active antiretroviral therapy initiation on CD4R T-cell repopulation in duodenal and rectal mucosa. / Hayes, Timothy L.; Asmuth, David; Critchfield, J. William; Knight, Thomas H.; McLaughlin, Bridget E.; Yotter, Tammy; McConnell, Delandy H.; Garcia, Juan Carlos; Pollard, Richard B; Shacklett, Barbara.
In: AIDS, Vol. 27, No. 6, 27.03.2013, p. 867-877.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Impact of highly active antiretroviral therapy initiation on CD4R T-cell repopulation in duodenal and rectal mucosa
AU - Hayes, Timothy L.
AU - Asmuth, David
AU - Critchfield, J. William
AU - Knight, Thomas H.
AU - McLaughlin, Bridget E.
AU - Yotter, Tammy
AU - McConnell, Delandy H.
AU - Garcia, Juan Carlos
AU - Pollard, Richard B
AU - Shacklett, Barbara
PY - 2013/3/27
Y1 - 2013/3/27
N2 - Objective: The objective of this study was to assess the effects of HAART initiation on CD4 T-cell repopulation and T-cell immune activation in rectal and duodenal mucosa. Design: The effects of HAART on the gastrointestinal tract remain controversial, and studies have reached different conclusions regarding its effectiveness at restoring mucosal CD4 T cells depending upon time of initiation, duration of treatment and gastrointestinal tract region studied. Methods: We obtained blood, rectal biopsies and duodenal biopsies from 14 chronically infected individuals at baseline and at 4-9 months post-HAART initiation. We examined CD4 T-cell frequencies in blood, rectum and duodenum at both time points, and performed a detailed assessment of CD4 T-cell phenotype, immune activation marker expression and HIV-specific CD8 T-cell responses in blood and rectal mucosa. Results: CD4 T-cell percentages increased significantly in blood, rectal and duodenal mucosa after 4-9 months of HAART (P1/40.02, 0.0005, 0.0002), but remained lower than in uninfected controls. HIV-specific CD8 T-cell responses in blood and rectal mucosa declined following HAART initiation (P1/40.0015, 0.021). CD8 T-cell coexpression of CD38 and HLA-DR in blood and mucosa, as well as plasma sCD14, declined significantly. CD28 expression on blood and mucosal CD8 T cells increased, whereas programmed death receptor-1 expression on blood HIV-specific CD4 and CD8 T cells decreased. Conclusion: Within the first months of HAART, limited CD4 T-cell reconstitution occurs in small and large intestinal mucosa. Nevertheless, decreased immune activation and increased CD28 expression suggest rapid immunological benefits of HAART despite incomplete CD4 T-cell reconstitution.
AB - Objective: The objective of this study was to assess the effects of HAART initiation on CD4 T-cell repopulation and T-cell immune activation in rectal and duodenal mucosa. Design: The effects of HAART on the gastrointestinal tract remain controversial, and studies have reached different conclusions regarding its effectiveness at restoring mucosal CD4 T cells depending upon time of initiation, duration of treatment and gastrointestinal tract region studied. Methods: We obtained blood, rectal biopsies and duodenal biopsies from 14 chronically infected individuals at baseline and at 4-9 months post-HAART initiation. We examined CD4 T-cell frequencies in blood, rectum and duodenum at both time points, and performed a detailed assessment of CD4 T-cell phenotype, immune activation marker expression and HIV-specific CD8 T-cell responses in blood and rectal mucosa. Results: CD4 T-cell percentages increased significantly in blood, rectal and duodenal mucosa after 4-9 months of HAART (P1/40.02, 0.0005, 0.0002), but remained lower than in uninfected controls. HIV-specific CD8 T-cell responses in blood and rectal mucosa declined following HAART initiation (P1/40.0015, 0.021). CD8 T-cell coexpression of CD38 and HLA-DR in blood and mucosa, as well as plasma sCD14, declined significantly. CD28 expression on blood and mucosal CD8 T cells increased, whereas programmed death receptor-1 expression on blood HIV-specific CD4 and CD8 T cells decreased. Conclusion: Within the first months of HAART, limited CD4 T-cell reconstitution occurs in small and large intestinal mucosa. Nevertheless, decreased immune activation and increased CD28 expression suggest rapid immunological benefits of HAART despite incomplete CD4 T-cell reconstitution.
KW - Gut
KW - HAART
KW - HIV
KW - Immune activation
KW - Mucosa
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=84876407945&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876407945&partnerID=8YFLogxK
U2 - 10.1097/QAD.0b013e32835d85b4
DO - 10.1097/QAD.0b013e32835d85b4
M3 - Article
C2 - 23262500
AN - SCOPUS:84876407945
VL - 27
SP - 867
EP - 877
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 6
ER -