Systemic immune activation in HIV and potential therapeutic options

Abstract

Context: Advancement in HIV treatment has evolved over the last two decades with the discovery of new drugs and approaches. Studies have demonstrated that HIV-infected individuals have elevated immune activation even during effective antiretroviral therapy. Persistently elevated immune activation has been one of the main obstacles against developing an effective approach for curing HIV.

Objective: This review examines the mechanism of microbial translocation in HIV-infected individuals and currently investigated potential therapeutic approaches.

Methods: We searched PubMed and Medline for peer-reviwed articles and recent HIV/AIDS conference abstracts and papers. Narrative review method was used since the objectives of the study were mechanism of microbial translocation and mechanism of action of multiple drugs against it.

Results: Microbial translocation occurs as a result of the disruption of epithelial barrier and immunological dysfunction within the intestinal tract due to defective tight junctions, loss of T_H17 type CD4⁺ T cells, impaired liver architecture, and depletion of intestinal myelomonocytic cells. Potent and effective way to intervene microbial translocation is to target the mechanism of actions involved in microbial translocation by restoration of beneficial microbiata with supplemental probiotics/prebiotics, increased clearance of microbial products from systemic circulation with targeted antibodies and restoration of intestinal integrity with antibiotics.

Conclusions: Number of promising drug molecules against microbial translocation are currently under various stages of trials and the results of these trials will hopefully contribute significantly toward effective therapeutic intervention. However, studies also need to explore the effect of combination drugs to abrogate microbial translocation.

• Inflammation
• lipopolysaccharide
• microbial translocation
• T-cell activation
• treatment