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 investigated the distribution of HIV-1 subtypes and the prevalence of HIV-1 drug resistance among HIV-infected antiretroviral-naive patients in Guangxi, southern China. A total of 144 subjects from Liuzhou or Nanning, two cities having the most HIV-infected cases in Guangxi, were enrolled. HIV-1 pol fragments were amplified and sequenced from plasma of all patients. In all, 124 sequences were obtained, with 67 from Liuzhou and 57 from Nanning. All sequences were subtyped by phylogenetic analysis and analyzed for antiretroviral resistance using the HIVdb program. Our data showed that the sequences from Liuzhou were subtyped as CRF01_AE (77.6%), CRF07_BC(20.9%), and BC (1.5%), respectively, and the sequences from Nanning as CRF01_AE (78.9%), CRF08_BC (15.8%), B (3.5%), and C (1.8%), respectively. Of the sequences 11.9% from Liuzhou and 28.1% from Nanning harbored drug resistance-associated mutations, but there were only two sequences with mutations associated with significantly reduced phenotypic susceptibility to antiretroviral drugs.

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Toll-like receptor 9 (TLR9) is one of the key sensors that recognize viral infection/replication in the host cells. Studies have demonstrated that methamphetamine (METH) dysregulated host cell innate immunity and facilitated HIV infection of macrophages. In this study, we present new evidence that METH suppressed TLR9-mediated anti-HIV activity in macrophages. Activation of TLR9 by its agonist CpG-ODN 2216 inhibits HIV replication, which was demonstrated by increased expression of TLR9, interferon (IFN)-α, IFN regulatory factor-7 (IRF-7), myeloid differentiation factor 88 (MyD88), and myxovirus resistance gene A (MxA) in macrophages. However, METH treatment of macrophages greatly compromised the TLR9 signaling-mediated anti-HIV effect and inhibited the expression of TLR9 downstream signaling factors. Dopamine D1 receptor (D1R) antagonists (SCH23390) could block METH-mediated inhibition of anti-HIV activity of TLR9 signaling. Investigation of the underlying mechanisms of the METH action showed that METH treatment selectively down-regulated the expression of TLR9 on macrophages, whereas it had little effect on the expression of other TLRs. Collectively, our results provide further evidence that METH suppresses host cell innate immunity against HIV infection by down-regulating TLR9 expression and its signaling-mediated antiviral effect in macrophages.