Microbial translocation linked to immune activation in HIV-infected children

Pilakka-Kanthikeel S. Pediatr Infect Dis J. 2012;doi:10.1097/INF.0b013e31824da0f5.

Gut microbial translocation persisted after control of HIV replication and was associated directly or indirectly with generalized immune activation, according to recent study findings published online.

Based on prior studies identifying the gut as a major site of HIV replication with loss of CD4 T cells, researchers conducted a 48-week study of collected plasma samples from antiretroviral therapy-experienced, immunologically stable but viremic HIV-infected children who were given a protease inhibitor-based regimen or dual nucleosides. Researchers examined whether gut microbial translocation represented a major stimulus for immune activation that persisted after control of virus replication.

Eighty-five HIV-infected children (aged 2 to 17 years) were enrolled in the study, with results of microbial translocation correlated with study data for T-cell immune activation, plasma virus load and CD4 counts designated virologic responders or virologic failures.

According to study results, lipopolysaccharide, bacterial 16S ribosomal DNA and soluble CD14 levels were increased in comparison to HIV-uninfected controls and did not decrease at week 44, even in patients designated as virologic responders.

T-cell immune activation was associated with virus load and soluble CD14 at study admission and linked with bacterial 16S ribosomal DNA and soluble CD14 at week 44 in study patients and in the group designated virologic failures. Alterations in bacterial 16S ribosomal DNA was linked with changes in immune activation, yet exhibited negative correlation with changes in CD4 counts.

“[Microbial translocation] is a characteristic feature of HIV disease in the perinatally HIV-infected population,” the researchers said. “In the cohort reported herein, change of therapy from suboptimal ART to more potent treatment, which was still substandard for the current era, did not lead to decrease in [microbial translocation], even in patients deemed virologic successes. The [microbial translocation] products showed a strong relationship with monocyte activation. which, in turn, correlated with T-cell activation. Long-term studies in children given early potent ART, as is the current standard of practice, could be informative for understanding gut healing and [microbial translocation].”

Disclosure: The researchers report financial support from NIH, International Maternal, the Pediatric and Adolescent AIDS Clinical Trials Group, the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health.

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