Impact of HIV infection and integrase strand transfer inhibitors-based treatment on gut virome
Authors: Villoslada-Blanco Pablo , Pérez-Matute Patricia , Íñiguez María , Recio-Fernández Emma , Daan Jansen , De Coninck Lander , Close Lila , Blanco-Navarrete Pilar , Metola Luis , Ibarra Valvanera , Alba Jorge , Matthijnssens Jelle , Oteo José A 
Published: April 2022

Viruses are the most abundant components of the microbiome in human beings with a significant impact on health and disease. However, the impact of human immunodeficiency virus (HIV) infection on gut virome has been scarcely analyzed. On the other hand, several studies suggested that not all antiretrovirals for treating HIV infection exert similar effects on the gut bacteriome, being the integrase strand transfers inhibitors (INSTIs) —first-choice treatment of naive HIV-infected patients nowadays— those associated with a healthier gut. Thus, the aim of this study was to evaluate the effects of HIV infection and INSTIs in first line of treatment on gut virome composition. To accomplish this objective, 26 non-HIV-infected volunteers, 15 naive HIV-infected patients and 15 INSTIs-treated HIV-infected patients were recruited and gut virome composition was analysed using shotgun sequencing. The results showed that bacteriophages are the most abundant and diverse viruses in the gut independent from the HIV-status and the use of treatment. HIV infection was accompanied by a decrease in phage richness which was reverted after INSTIs-based treatment (p<0.01 naive vs. control Richness index and p<0.05 naive vs. control Fisher’s alpha index). β-diversity of phages revealed that samples from HIV-infected samples clustered separately from those belonging to the control group (padj<0.01 naive vs. control and padj<0.05 INSTIs vs. control). However, it is worth mentioning that samples coming from INSTIs-treated patients were more grouped than those from naive patients. Differential abundant analysis of phages showed an increase of Caudoviricetes class in the naive group compared to control the group (padj<0.05) and a decrease of Malgrandaviricetes class in the INSTIs-treated group compared to the control group (padj<0.001). Besides, it was observed that INSTIs-based treatment was not able to reverse the increase of lysogenic phages associated with HIV infection (p<0.05 vs. control) or to modify the decrease observed on the relative abundance of Proteobacteria-infecting phages (p<0.05 vs. control). To sum up, 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 not only at bacterial but also at viral level, which opens several opportunities for new studies focused on microbiota-based therapies.

Author summary

The impact of human immunodeficiency virus (HIV) infection and the effects of integrase strand transfer inhibitors (INSTIs)-based treatments —first-choice treatment of naive HIV-infected patients nowadays— on gut virome are unknown. In this study, we have confirmed that phages are the most abundant viral component of the human gut virome. Besides, we have described for the first time that INSTIs-based treatments are able to partially restore gut dysbiosis induced by HIV infection not only at bacteria but also at viral level. This fact opens new opportunities for future studies and approaches focused on microbiota-based therapies in the context of HIV infection and treatment.