CROI 2014: Early Antiretroviral Therapy May Limit Gut Damage and Immune Activation

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Starting antiretroviral therapy (ART) at the earliest stage of HIV infection can help prevent immune cell dysregulation that contributes to destruction of the gut lining and promotes systemic immune over-activation, according to a study presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2014) last week in Boston.

When HIV disrupts the gut lining, bacteria can leak out -- known as bacterial translocation -- and trigger a systemic or whole-body inflammatory response. Persistent inflammation and excessive immune activation are thought to contribute to non-AIDS conditions such as cardiovascular disease and cognitive impairment in people with HIV.

Alexandra Schuetzfrom the Armed Forces Research Institute of Medical Sciences and colleagues in Thailand looked at whether early ART during acute HIV infection might limit damage to the intestinal mucosal barrier.

In particular, they measured Th17 cells, a type of T-cell that is instrumental in maintenance of the gut epithelial barrier, the researchers explained as background. These cells produce cytokines including involved in inflammatory response, including interleukin 17 (IL-17). Disruption of the normal balance between Th17 cells and regulatory T-cells (T-regs) that dampen the response contributes to excessive immune activation.

This analysis included 34 participants with acute HIV infection (median duration 15 days) at Fiebig stages FI (n=13) or FIII (n=21), identified out of nearly 53,000 screened samples. In addition, 5 HIV-uninfected individuals and 9 treatment-naive people with chronic HIV infection (6-12 months post-infection; median 298 days) matched for age and sex served as controls. Most participants were men who have sex with men and the mean age was approximately 28 years.

Fiebig stages indicate when HIV RNA, p24 antigen, and antibodies become detectable. Stage FI indicates initial ramp-up of viral replication, with peak viral load occurring during stage FIV.

Participants underwent sigmoid biopsies to obtain gut tissue samples at baseline and at 6 and 24 months after starting ART (27 and 16 people had the second and third biopsies, respectively).

Results

"Initiation of ART at Fiebig I prevents loss of mucosal Th17 cells and function," the researchers summarized. "Initiation of ART in Fiebig III cannot restore the initial loss of multifunctional mucosal Th17 cells, despite partial recovery of Th17 cells."

These findings, they concluded, "emphasize the importance of strategies to prevent loss of mucosal Th17 cell function and argue for early and aggressive treatment intervention."

3/14/14

Reference

A Schuetz, Y Phuang-Ngern, R Rerknimitr, et al. Early ART Initiation Prevents Disruption of the Mucosal Barrier and Subsequent T-Cell Activation. 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014). Boston, March 3-6. Abstract 77.