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Leakage of Gut Bacteria May Continue in People with Low-level HIV Despite Antiretroviral Therapy

Microbial translocation, or leakage of bacteria from the gut, was detected in patients who continued to show low-level HIV replication despite being on highly active antiretroviral therapy (HAART), researchers found in a study reported in the December 2009 Journal of Clinical Virology. Released bacteria and the substances they produce can cause systematic immune activation and inflammation, contributing to problems throughout the body.

Increasing evidence indicates that even low-level ongoing HIV replication is associated with a wide variety of problems, including cardiovascular disease and possible acceleration of the aging process, well before serious immune system damage occurs. Many experts believe chronic inflammation triggered by the virus plays a key role.

In the present study, Silvia Baroncelli from the Istituto Superiore di Sanità in Rome, Italy, and colleagues aimed to assess the effect of residual viral replication (< 50copies/mL) on plasma levels of lipopolysaccharide (LPS) in HIV positive patients on HAART. They also evaluated changes in LPS levels during repeated ART interruptions not exceeding 2 months duration.

LPS (also known as endotoxin) is a component of bacterial cell walls that triggers immune activation. In people with HIV, plasma LPS levels have been shown to be a marker for bacteria -- which naturally live in gut -- escaping into the bloodstream through leaky intestinal linings, a process known as bacterial translocation. Ongoing inflammation and the toxic effects of LPS in the blood contribute to a variety of problems including blood vessel damage and neurocognitive impairment.

The investigators measured plasma LPS levels in 44 HIV positive participants during ART (designated T0) and at day 15 of the first and fourth cycles of ART interruption. They also studied a control group of 10 healthy HIV negative subjects.

Residual plasma HIV RNA was measured at T0 using an ultra-sensitive method with limit of detection of 2.5copies/mL. Participants with viral load less than 2.5copies/mL (fully suppressed) were compared to those with 2.5-50copies/mL (partially suppressed).

Results

• At T0, plasma LPS levels were comparable in fully suppressed and HIV negative participants.
• However, LPS levels were higher in those with partial HIV suppression (P=0.049).
• After 4 cycles of ART interruption, LPS levels did not change significantly, but were lower in fully suppressed compared with partially suppressed participants (P=0.020).
• There was an inverse correlation between LPS levels and CD4 cell count only in the partially suppressed group.

"A reduced degree of microbial translocation was seen in subjects with a more complete suppression of viral replication," the study authors concluded. "Repeated HAART interruptions had no significant impact on plasma LPS levels."

Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.

1/08/10

Reference

S Baroncelli, CM Galluzzo, MF Pirillo, and others. Microbial translocation is associated with residual viral replication in HAART-treated HIV+ subjects with < 50copies/ml HIV-1 RNA. Journal of Clinical Virology 46(4): 367-370 (Abstract). December 2009.