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.
Highlights
Increased bacterial translocation and alterations to gut microbiota composition have been described in HIV infection and contribute to immune activation and inflammation
There were no differences concerning the different families of combined antiretroviral therapy (cART) used patients in the nucleoside reverse transcriptase inhibitors (NRTIs)+integrase strand transfer inhibitors (INSTIs) group had a higher incidence of AIDS (p = 0.013)
No differences were observed for the total length on treatment, a slightly longer time on treatment was observed in the INSTI group, showing significant differences compared with the NRTIs+nucleoside reverse transcriptase inhibitors (NNRTIs) group (p = 0.048)
Summary
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). 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. Loss of immune protection of the intestinal mucosa allows translocation of microbial products (such as lipopolysaccharides) into the lamina propria of the gastrointestinal tract and, eventually, into the systemic circulation [2,3,4] This is known as bacterial translocation (BT), which was firstly described in HIV-infected patients in 2006 [5,6]. We tested whether these families of antiretrovirals were able to restore GM composition compared with an uninfected population
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