Differential effects of antiretrovirals on microbial translocation and gut microbiota composition of HIV‐infected patients

Abstract

Introduction: Increased bacterial translocation and alterations to gut microbiota composition have been described in HIV infection and contribute to immune activation and inflammation. These effects persist despite combined antiretroviral therapy (cART). However, the contribution of different cART combinations has not yet been investigated. The aim of this study was to analyse the long-term effects of different combinations of cART on bacterial translocation and gut microbiota composition in HIV-infected patients. Methods: We carried out a cross-sectional study of 45 HIV-infected patients on cART, classified as nucleoside reverse transcriptase inhibitors (NRTIs)+ protease inhibitors (PIs) (n = 15), NRTIs+ non-nucleoside reverse transcriptase inhibitors (NNRTIs) (n = 22), and NRTIs+ integrase strand transfer inhibitors (INSTIs) (n = 8). Untreated HIV-infected patients (n = 5) and non-infected volunteers (n = 21) were also included. Soluble markers of bacterial translocation and inflammation were measured and gut microbiota composition was analysed using 16S rDNA pyrosequencing (Illumina MiSeq). Results: The NRTIs+INSTIs regimen was associated with levels of systemic inflammation that were similar to uninfected controls. The reduction in faecal bacterial diversity induced by HIV infection was also restored by this regimen. HIV infection was more closely related to changes in lower taxonomic units and diversity rather than at the phylum level. The NRTIs+PIs regimen showed the highest reduction in bacterial species, whereas NRTIs+INSTIs induced a minor loss of bacterial species and a significant increase in others. Conclusions: Our study demonstrated that INSTI-based ART was associated with levels of systemic inflammation and microbial diversity similar to that of uninfected controls. The role of INSTIs other than raltegravir needs to be further investigated. Patients on the NRTIs+PIs regimen presented the highest reduction in bacterial species compared with other antiretrovirals and naive patients. Thus, different cART regimens are associated with diverse profiles in gut microbiota composition. Longitudinal and functional studies are needed to better understand these findings.

Impact of antiretroviral drugs on the microbiome

“…Indeed, despite vast improvements in drug tolerability and overall drug safety of contemporary drugs, different ARV combinations have different side effects and this could differentially affect how the gut microbiome responds: reduced diversity versus increased diversity, restoration versus further dysbiosis, and so on. Surprisingly, however, only a handful of articles have addressed the differential effects of ARV drugs on the gut microbiome, microbial translocation, enterocyte damage and inflammation/immune activation [ 29 , 30 ▪▪ , 31 ▪▪ ]. Improving our understanding of the impact of ART and different ARV combinations is needed to draw a complete picture as more HIV-infected individuals will have access to ART and become ART-experienced, and as more people are using ART as preexposure prophylaxis (PrEP) in the absence of HIV infection.…”

Type I interferon and HIV: Subtle balance between antiviral activity, immunopathogenesis and the microbiome

“…In this context, an overall enrichment of members of the phylum Proteobacteria and decreased abundances of Firmicutes were observed in the mucosal tissues and stool samples of both untreated and treated HIV-1 infected individuals [144,145]. Unexpectedly, a significant decrease in the abundance of Firmicutes was observed in HIV-infected patients using NRTIs + PIs compared to uninfected controls, suggesting that specific HAART regimens are associated with diverse profiles in gut microbiota composition [151].…”

Clinical round-up

“…This paper by Villanueva-Millán et al 4 looks at the effect of different ARV classes on gut microbiota and microbial translocation. They undertook a cross-sectional study of 45 stable patients with HIV (viral load <20 for >6 months) on different ARV drug classes—nucleoside reverse transcriptase inhibitor (NRTI)+protease inhibitor (PI) (15 patients), NRTI+integrase inhibitor (INI) (8) and NRTI+non-nucleoside reverse transcriptase inhibitor (NNRTI) (22)—and compared them to the gut microbiota of 21 uninfected volunteers and 5 patients with HIV not on ARV treatment (mean viral load of 54 010 copies/mL (3550–71 800)).…”