BackgroundThe immune activation caused by microbial translocation has been considered to be a major driver of HIV infection progression. The dysbiosis of gut microbiota has been demonstrated in HIV infection, but the interplay between gut microbiota and its metabolites in the pathogenesis of HIV is seldom reported.MethodsWe conducted a case-controlled study including 41 AIDS patients, 39 pre-AIDS patients and 34 healthy controls. Both AIDS group and pre-AIDS group were divided according to clinical manifestations and CD4 + T cell count. We collected stool samples for 16S rDNA sequencing and untargeted metabolomics analysis, and examined immune activation and microbial translocation for blood samples.ResultsThe pre-AIDS and AIDS groups had higher levels of microbial translocation and immune activation. There were significant differences in gut microbiota and metabolites at different stages of HIV infection. Higher abundances of pathogenic bacteria or opportunistic pathogen, as well as lower abundances of butyrate-producing bacteria and bacteria with anti-inflammatory potential were associated with HIV severity. The metabolism of tryptophan was disordered after HIV infection. Lower level of anti-inflammatory metabolites and phosphonoacetate, and higher level of phenylethylamine and polyamines were observed in HIV infection. And microbial metabolic pathways related to altered metabolites differed. Moreover, disrupted metabolites contributed by altered microbiota were found to be correlated to microbial translocation and immune activation.ConclusionsMetabolites caused by dysbiosis of gut microbiota and related metabolic function are correlated to immune activation and microbial translocation, suggesting that the effect of microbiota on metabolites is related to intestinal barrier disruption in HIV infection.

We reported an HIV-naïve patient from a resource-limited area who was detected with multiple resistance sites associated with nucleoside reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs) after the failure of the initial antiviral regimen dolutegravir/lamivudine (DTG/3TC) and subsequent Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). On May 8, 2021, a 53-year-old man was diagnosed with AIDS, Marneffei talaromycosis and fungal esophagitis, and was suspected of having tuberculosis (TB) in Guangxi, China. His baseline HIV RNA was 559,000 copies/mL and the CD4 count was 12 cells/µL, but resistance genotype testing was not performed. The patient remained immunosuppressed (CD4 count 3 cells/µL) after 12 weeks of initial antiviral treatment (ART) with DTG/3TC. After he was switched to BIC/FTC/TAF and started anti-TB treatment, the viral load (HIV RNA 163,200 copies/mL) was not effectively controlled, and there were multiple NRTIs drug-resistant mutations (D67N, K70R, M184V, T215V, K219Q) and INSTIs mutations (E138K, G140A, S147SG, Q148R). This suggested that in resource-limited areas, for HIV-naïve patients in advanced stages with active opportunistic infections, HIV RNA>500,000 copies/mL, and low CD4 count, baseline resistance testing and increased HIV RNA testing frequency should be recommended, DTG/3TC was not recommended as initiation, and opportunistic infections should be treated promptly. In addition, switching to other INSTIs was not recommended in the absence of resistance testing and ineffective use of DTG.