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

Oral microbiome is the second largest microbial community in humans after gut. Human immunodeficiency virus (HIV) infection triggers an impairment of the immune system which could favour the growth and the colonization of pathogens in the oral cavity, and this dysbiosis has been associated with oral manifestations that worsen the quality of life of these patients. Antiretroviral therapy (ART) could also drive changes in specific oral bacterial taxa associated with such periodontal diseases. Integrase strand transfer inhibitors (INSTIs), therapy of choice in the treatment of naive HIV-patients, are able to reverse the impact of HIV infection on systemic inflammation, gut permeability, and gut bacterial diversity/richness. The objective of this study was to analyse the effects of HIV infection per se and INSTIs on salivary bacteriome composition, taking into consideration other factors such as smoking, that could also have a significant impact on oral microbiome. To accomplish this objective, 26 non-HIV-infected volunteers and 30 HIV-infected patients (15 naive and 15 under INSTIs-regimen) were recruited. Salivary samples were collected to measure lysozyme levels. Oral bacteriome composition was analysed using 16S rRNA gene sequencing. Naive HIV-infected patients showed statistically higher levels of lysozyme compared to controls (p < 0.001) and INSTIs-treated patients (p < 0.05). Our study was unable to detect differences in α nor ß-diversity among the three groups analysed, although significant differences in the abundance of some bacterial taxonomical orders were detected (higher abundance in the phylum Pseudomonadota, in the order Acholeplasmatales, and in the genera Ezakiella and Acholeplasma in the naive group compared to controls; and higher abundance in the phylum Mycoplasmatota, in the order Acholeplasmatales, and in the genera Acholeplasma and uncultured Eubacteriaceae bacterium in the INTIs-treated HIV-infected patients compared to controls). These differences seem to be partially independent of smoking habit. HIV infection and INSTIs effects on oral microbiota seem not to be very potent, probably due to the modulation of other factors such as smoking and the greatest outward exposure of the oral cavity.

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

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. ß-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.

Integrase Inhibitors Partially Restore Bacterial Translocation, Inflammation and Gut Permeability Induced by HIV Infection: Impact on Gut Microbiota.

INTRODUCTION: Human immunodeficiency virus (HIV) infection can be considered a chronic disease thanks to the extended use of antiretroviral treatment (ART). In this context, low-grade chronic inflammation related to gut microbiota (GM) dysbiosis and bacterial translocation (BT) among other factors has been observed despite the use of ART. In addition, different ART regimens have demonstrated differential impacts on GM. However, the role of novel integrase strand transfer inhibitors (INSTIs) has not been investigated yet. The aim of this study was to analyse the effects of INSTIs in first-line of treatment on markers of BT, inflammation, cardiovascular risk, gut permeability and GM composition and derived short-chain fatty acids. METHODS: Twenty-six non-HIV-infected volunteers and 30 HIV-infected patients (15 naïve and 15 under INSTIs regimen) were recruited. Blood samples were extracted to analyse biochemical parameters and markers of BT, inflammation, cardiovascular risk, gut permeability and bacterial metabolism. GM composition was analysed using 16S rRNA gene sequencing. RESULTS: Our results showed that HIV infection increased BT, inflammation, cardiovascular risk and gut permeability, whereas INSTIs counteracted these effects. Regarding GM, the reduction in bacterial richness induced by HIV infection was restored by INSTIs. Beta diversity revealed that HIV-infected people were separated from the control group independently of treatment. CONCLUSIONS: Current antiretroviral regimens based on INSTIs are able to reverse the impact of HIV infection on BT, systemic inflammation, gut permeability and bacterial diversity/richness, reaching similar levels to those observed in an uninfected/control population. These results suggest a protective role of INSTIs in disease progression, subsequent immune activation and in the development of future age-related complications such as cardiovascular events.