In this session, 4 different speakers discussed the chronic inflammatory state that persists despite effective viral suppression with current ART regimens.
The first speaker (G Marchetti, Milan) highlighted that there is a persistent depletion of CD 4 cells in the gut despite normalisation in the peripheral blood. There is also persistent damage to the gut tight epithelial barrier despite ART. The altered gut tight epithelial barrier maybe a driver of inflammation. This speaker also highlighted the fact that no matter which ART regimen is employed there is a similar reduction of T cell activation with effective viral suppression.
The second speaker (P. Hunt, San Francisco) focussed on immune activation as a predictor of morbidity/mortality during ART. As we know,age associated morbidities are increased in treated HIV infection. Inflammatory markers are higher in treated HIV disease compared with HIV sero-negatives when adjusted for demographics and CV risk factors. Chronic immune activation may also cause lymphoid tissue fibrosis. He showed a graph which demonstrated that a single measurement of IL 6 or D-dimmer predicts morbidity or mortality over the next decade. This indicates that some people are more susceptible to the inflammatory state of HIV than others. However, bio markers that predict disease most strongly are not necessarily the best interventional targets.
The third speaker (N. Sander, Texas) looked at the role of interferon 1 in chronic treated HIV. A lot of the data was based on nonhuman models. Overal, type 1 interferons can improve protection against infection but because of immune system activation may not be suitable long term as adjuvant therapy. This raised the question of whether there maybe a benefit of selective activation or blockade of the different pathways induced by IFN-1.
Finally, I. Pandreas (Pittsburgh) discussed approaches to reduce microbial translocation as a means of reducing immune activation. These were with sevelamer and rifaximin. However, in the presence of profound gut damage, these approaches are unlikely to have significant benefit. She then examined other interfering factors on gut function such alcohol and fatty diets. These results were based on nonhuman models. Probiotics were shown to have benefit for gastrointestinal immunity in SIV-infected macaques. This highlighted that lifestyle factors should be taken into consideration when designing clinical trials as they may all impact on immune system activation. This also highlighted that therapies which target the underlying cause of immune activation and inflammation may be more effective than those aiming at reducing various bio markers increased during HIV infection.
All of these presentations highlight how complex and confusing the immune activation and inflammation process is in HIV infection!