Abstract
Background: Gut microbial translocation (MT) is considered a major cause of immune activation (IA) and failure of immune reconstitution in HIV infection. This study investigated the relationship of virus replication, IA, CD4 counts and MT in HIV-infected children. Methods: Lipopolysaccharide, bacterial 16S ribosomal DNA (16SrDNA) and soluble CD14 (sCD14) levels were determined in prospectively collected, stored plasma samples from the Pediatric AIDS Clinical Trials Group Protocol P338, a 48-week study initiated in 1997 to compare efficacy of dual nucleosides with a ritonavir-containing regimen. Results of MT were correlated with study data for T cell IA, plasma viral load and CD4 counts in 85 HIV-infected children (ages 2-17 years) designated as virologic responders or virologic failures (VF) at week 44 based on a cutoff of 400 HIV RNA copies/mL. Results: Levels of plasma lipopolysaccharide, 16SrDNA and sCD14 were increased in comparison with HIV-uninfected controls and did not decrease at week 44 even in virologic responders. T cell IA was correlated with viral load and sCD14 at entry and with 16SrDNA and sCD14 at week 44 in total patients and in the VF group. Changes in 16SrDNA correlated with changes in IA and negatively with changes in CD4 counts. 16SrDNA was correlated with sCD14 but not with lipopolysaccharide. Conclusions: MT persists after 44 weeks of antiretroviral therapy in VS and VF patients. In VF, 16SrDNA exhibited relationships to monocyte and T cell IA and CD4 counts but not with viral load, suggesting a dominant role for MT in disease pathogenesis in HIV-infected children.
| Original language | English |
|---|---|
| Pages (from-to) | 583-591 |
| Number of pages | 9 |
| Journal | Pediatric Infectious Disease Journal |
| Volume | 31 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2012 |
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Keywords
- 16SrDNA
- HIV infection
- Immune activation
- Lipopolysaccharide
- Microbial translocation
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Infectious Diseases
- Microbiology (medical)
Cite this
Increased gut microbial translocation in HIV-infected children persists in virologic responders and virologic failures after antiretroviral therapy. / Pilakka-Kanthikeel, Sudheesh; Huang, Sharon; Fenton, Terry; Borkowsky, William; Cunningham, Coleen K.; Pahwa, Savita G.
In: Pediatric Infectious Disease Journal, Vol. 31, No. 6, 01.06.2012, p. 583-591.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Increased gut microbial translocation in HIV-infected children persists in virologic responders and virologic failures after antiretroviral therapy
AU - Pilakka-Kanthikeel, Sudheesh
AU - Huang, Sharon
AU - Fenton, Terry
AU - Borkowsky, William
AU - Cunningham, Coleen K.
AU - Pahwa, Savita G
PY - 2012/6/1
Y1 - 2012/6/1
N2 - Background: Gut microbial translocation (MT) is considered a major cause of immune activation (IA) and failure of immune reconstitution in HIV infection. This study investigated the relationship of virus replication, IA, CD4 counts and MT in HIV-infected children. Methods: Lipopolysaccharide, bacterial 16S ribosomal DNA (16SrDNA) and soluble CD14 (sCD14) levels were determined in prospectively collected, stored plasma samples from the Pediatric AIDS Clinical Trials Group Protocol P338, a 48-week study initiated in 1997 to compare efficacy of dual nucleosides with a ritonavir-containing regimen. Results of MT were correlated with study data for T cell IA, plasma viral load and CD4 counts in 85 HIV-infected children (ages 2-17 years) designated as virologic responders or virologic failures (VF) at week 44 based on a cutoff of 400 HIV RNA copies/mL. Results: Levels of plasma lipopolysaccharide, 16SrDNA and sCD14 were increased in comparison with HIV-uninfected controls and did not decrease at week 44 even in virologic responders. T cell IA was correlated with viral load and sCD14 at entry and with 16SrDNA and sCD14 at week 44 in total patients and in the VF group. Changes in 16SrDNA correlated with changes in IA and negatively with changes in CD4 counts. 16SrDNA was correlated with sCD14 but not with lipopolysaccharide. Conclusions: MT persists after 44 weeks of antiretroviral therapy in VS and VF patients. In VF, 16SrDNA exhibited relationships to monocyte and T cell IA and CD4 counts but not with viral load, suggesting a dominant role for MT in disease pathogenesis in HIV-infected children.
AB - Background: Gut microbial translocation (MT) is considered a major cause of immune activation (IA) and failure of immune reconstitution in HIV infection. This study investigated the relationship of virus replication, IA, CD4 counts and MT in HIV-infected children. Methods: Lipopolysaccharide, bacterial 16S ribosomal DNA (16SrDNA) and soluble CD14 (sCD14) levels were determined in prospectively collected, stored plasma samples from the Pediatric AIDS Clinical Trials Group Protocol P338, a 48-week study initiated in 1997 to compare efficacy of dual nucleosides with a ritonavir-containing regimen. Results of MT were correlated with study data for T cell IA, plasma viral load and CD4 counts in 85 HIV-infected children (ages 2-17 years) designated as virologic responders or virologic failures (VF) at week 44 based on a cutoff of 400 HIV RNA copies/mL. Results: Levels of plasma lipopolysaccharide, 16SrDNA and sCD14 were increased in comparison with HIV-uninfected controls and did not decrease at week 44 even in virologic responders. T cell IA was correlated with viral load and sCD14 at entry and with 16SrDNA and sCD14 at week 44 in total patients and in the VF group. Changes in 16SrDNA correlated with changes in IA and negatively with changes in CD4 counts. 16SrDNA was correlated with sCD14 but not with lipopolysaccharide. Conclusions: MT persists after 44 weeks of antiretroviral therapy in VS and VF patients. In VF, 16SrDNA exhibited relationships to monocyte and T cell IA and CD4 counts but not with viral load, suggesting a dominant role for MT in disease pathogenesis in HIV-infected children.
KW - 16SrDNA
KW - HIV infection
KW - Immune activation
KW - Lipopolysaccharide
KW - Microbial translocation
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U2 - 10.1097/INF.0b013e31824da0f5
DO - 10.1097/INF.0b013e31824da0f5
M3 - Article
VL - 31
SP - 583
EP - 591
JO - Pediatric Infectious Disease Journal
JF - Pediatric Infectious Disease Journal
SN - 0891-3668
IS - 6
ER -