SUMMARYIn pathogenic simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections, the translocation of microbial products from the gastrointestinal (GI) tract to portal and systemic circulation has been proposed as a major driver of the chronic immune activation that is associated with disease progression. Consistently, microbial translocation is not present in nonpathogenic SIV infections of natural host species.In vivostudies demonstrated that HIV/SIV-associated microbial translocation results from a series of immunopathological events occurring at the GI mucosa: (i) early and severe mucosal CD4+depletion, (ii) mucosal immune hyperactivation/persistent inflammation; (iii) damage to the integrity of the intestinal epithelium with enterocyte apoptosis and tight junction disruption; and (iv) subverted the gut microbiome, with a predominance of opportunistic bacteria. Directin situevidence of microbial translocation has been provided for SIV-infected rhesus macaques showing translocated microbial products in the intestinal lamina propria and distant sites. While the mechanisms by which microbial translocation causes immune activation remain controversial, a key pathogenic event appears to be innate immunity activation via Toll-like receptors and other pathogen recognition receptors. Accumulating clinical observations suggest that microbial translocation might affect HIV disease progression, response to therapy, and non-AIDS comorbidities. Given its detrimental effect on overall immunity, several interventions to prevent/block microbial translocation are currently under investigation as novel therapeutic agents for HIV/AIDS.

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Patients with inefficient CD4+ T-cell recovery on virogically suppressive highly active antiretroviral therapy constitute a major clinical hurdle given the threat of HIV/AIDS disease progression. We show heightened circulating lipopolysaccharide associated with plasma enterobacterial DNA and highly activated Ki67+CD4+CD8+ in 24 immunologic-nonresponders (CD4+ T-cell < or = 200; HIV-RNA < or = 50) compared with 11 full responders (CD4+ T-cell > or= 400; HIV-RNA < or = 50). These data provide novel insight into INRs pathogenesis, since they correlate augmented systemic translocation of microbial bioproducts with T-cell hyperactivation.

Up to 30% of human immunodeficiency virus (HIV)-infected patients who are receiving long-term highly active antiretroviral therapy do not exhibit a marked increase in the CD4(+) T cell count, despite achieving complete suppression of the HIV load. These patients are referred to as "immunological nonresponders." When treating immunological nonresponders, the practicing clinician has several questions, including questions about the clinical risk associated with persistent immunodeficiency and about possible approaches to treatment that would provide clinical and immunological benefits. However, tentative answers to these questions require investigations of the mechanisms that underlie the lack of immune recovery, because only the deepest comprehension of the immunological gaps underlying functional defects will allow administration of highly targeted and efficacious treatment strategies. The aim of our review is to provide a thorough assessment of the clinical implications of a lack of increase in the CD4(+) T cell count in immunological nonresponders, to examine the immunological gaps limiting recovery of the CD4(+) T cell count, and to note possible therapeutic avenues, which may offer clinicians guidance regarding how to most efficaciously treat these critical patients.

Our results show that impairment of the gastrointestinal tracts in human immunodeficiency virus (HIV)-positive patients is present in the early phases of HIV disease. This impairment is associated with alterations in gut microbiota and intestinal inflammatory parameters. These findings support the hypothesis that alterations at the gastrointestinal-tract level are a key factor in HIV pathogenesis.

Prevalence of anxiety/depression was investigated in 105 COVID‐19 patients at 1‐3 months from virological clearance by Hospital Anxiety and Depression Scale (HADS‐A/D). 30% of patients displayed pathological HADS‐A/D, 52.4% showed persistent symptoms. Pathological HADS‐A/D patients more commonly reported symptom persistence, even after adjustment for age, gender, disease severity. Psychological assessments should be encouraged in COVID‐19 patients’ follow‐up. This article is protected by copyright. All rights reserved.

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Circulating LPS in the first years of chronic HIV infection is a strong predictor of disease progression independent of CD4(+) cell count and HIV viraemia and may be considered a candidate biomarker for HIV monitoring and evaluation in clinical trials.