Impact of HIV infection and integrase strand transfer inhibitors-based treatment on the gut virome

Abstract

Viruses are the most abundant components of the human gut microbiome with a significant impact on health and disease. The effects of human immunodeficiency virus (HIV) infection on gut virome has been scarcely analysed. Several studies suggested that integrase strand transfers inhibitors (INSTIs) are associated with a healthier gut. Thus, the objective of this work was to evaluate the effects of HIV infection and INSTIs on gut virome composition. 26 non-HIV-infected volunteers, 15 naive HIV-infected patients and 15 INSTIs-treated HIV-infected patients were recruited and their gut virome composition was analysed using shotgun sequencing. Bacteriophages were the most abundant and diverse viruses present in gut. HIV infection was accompanied by a decrease in phage richness which was reverted after INSTIs-based treatment. β-diversity of phages revealed that samples from HIV-infected patients clustered separately from those belonging to the control group. Differential abundant analysis showed an increase in phages belonging to Caudoviricetes class in the naive group and a decrease of Malgrandaviricetes class phages in the INSTIs-treated group compared to the control group. Besides, it was observed that INSTIs-based treatment was not able to reverse the increase of lysogenic phages associated with HIV infection or to modify the decrease observed on the relative abundance of Proteobacteria-infecting phages. Our study describes for the first time the impact of HIV and INSTIs on gut virome and demonstrates that INSTIs-based treatments are able to partially restore gut dysbiosis at the viral level, which opens several opportunities for new studies focused on microbiota-based therapies.

Beyond the effects of HIV infection and integrase inhibitors-based therapies on oral bacteriome

“…Contrary to the results observed in our previous works focused on gut microbiota [23,24], the effects of HIV infection and INSTIs on oral microbiota seem to be not very signi cant, probably due to the modulation of other factors such as smoking, and the greatest outward exposure of the oral cavity.…”

“…Previous works from our group demonstrated that ARTs based on integrase strand transfer inhibitors (INSTIs) were associated with levels of systemic in ammation, bacterial translocation, and microbial diversity similar to those observed in uninfected controls [22]. Besides, these studies showed a clear impact of HIV-infection and INSTIs-based treatments on gut bacteriome [23] and virome [24]. However, how long-term ART, and speci cally INSTIs, modulate oral microbiota in HIV-infected patients and the implications of these effects on health deserve further research.…”

“…The main characteristics of the recruited population is showed as Supplementary Table 1 [23,24]. Of note, smoking habits were higher in the naive group and INSTIs-treated group compared to the controls (11.54% vs. 46.67% and 66.67%, respectively).…”

“…HIV-infected patients (naive and under ART) as well as the non-infected volunteers used as "healthy" controls were recruited from the Infectious Diseases Department at Hospital Universitario San Pedro (HUSP) and from the Health Care Center "Siete Infantes de Lara" (Logroño, Spain) from March 2019 to February 2021, as previously described [23,24]. Supplementary Fig.…”

Gut Phageome—An Insight into the Role and Impact of Gut Microbiome and Their Correlation with Mammal Health and Diseases

“…This increased level of lysogenic phages remained even after treatment with integrase strand transfer inhibitors (INSTIs). [78] Liver cirrhosis Humans Patients with liver cirrhosis showcased prevalent levels in Siphoviridae, Podoviridae, and Myoviridae.…”