Some HIV-infected individuals receiving ART develop low-level viremia(LLV),with a plasma viral load of 50-1000 copies/mL.Persistent low-level viremia is associated with subsequent virologic failure.The peripheral bloo...Some HIV-infected individuals receiving ART develop low-level viremia(LLV),with a plasma viral load of 50-1000 copies/mL.Persistent low-level viremia is associated with subsequent virologic failure.The peripheral blood CD4^(+)T cell pool is a source of LLV.However,the intrinsic characteristics of CD4^(+)T cells in LLV which may contribute to low-level viremia are largely unknown.We analyzed the transcriptome profiling of peripheral blood CD4^(+)T cells from healthy controls(HC)and HIV-infected patients receiving ART with either virologic sup-pression(VS)or LLV.To identify pathways potentially responding to increasing viral loads from HC to VS and to LLV,KEGG pathways of differentially expressed genes(DEGs)were acquired by comparing VS with HC(VS-HC group)and LLV with VS(LLV-VS group),and overlapped pathways were analyzed.Characterization of DEGs in key overlapping pathways showed that CD4^(+)T cells in LLV expressed higher levels of Th1 signature transcription factors(TBX21),toll-like receptors(TLR-4,-6,-7 and-8),anti-HIV entry chemokines(CCL3 and CCL4),and anti-IL-1βfactors(ILRN and IL1R2)compared to VS.Our results also indicated activation of the NF-κB and TNF signaling pathways that could promote HIV-1 transcription.Finally,we evaluated the effects of 4 and 17 tran-scription factors that were upregulated in the VS-HC and LLV-VS groups,respectively,on HIV-1 promoter activity.Functional studies revealed that CXXC5 significantly increased,while SOX5 markedly suppressed HIV-1 tran-scription.In summary,we found that CD4^(+)T cells in LLV displayed a distinct mRNA profiling compared to that in VS,which promoted HIV-1 replication and r+eactivation of viral latency and may eventually contribute to virologic failure in patients with persistent LLV.CXXC5 and SOX5 may serve as targets for the development of latency-reversing agents.展开更多
Opportunistic infections caused by viruses,bacteria,fungi,and parasites,are commonly reported in hospitalized human immunodeficiency virus(HIV)-positive patients,but their detrimental contribution to disease severity ...Opportunistic infections caused by viruses,bacteria,fungi,and parasites,are commonly reported in hospitalized human immunodeficiency virus(HIV)-positive patients,but their detrimental contribution to disease severity remains under explored.In this study,we examined the coinfection profiles of 126 HIV-positive patients with suspected respiratory,bloodstream,or neurological infections.Lower respiratory tract(LRT)samples,cerebrospinal fluid,and blood samples collected within the first seven days of admission were subjected to metagenomic next-generation sequencing(mNGS).Additionally,a multiplex polymerase chain reaction(PCR)detection kit to identify ten commonly known respiratory pathogens was applied to the LRT samples.Of 126 HIV-positive patients,111(88.1%)were coinfected with at least one known virus.Epstein-Barr virus(EBV)(71/111,64.0%),human cytomegalovirus(HCMV)(64/111,57.7%),and torque teno virus(TTV)(63/111,56.8%)were the three most prevalent coinfected viruses.Fungal coinfections(58/126,46.0%)and bacterial coinfections(47/126,37.3%)were less frequent than viral coinfections.Higher viral loads of coinfection were associated with fungal coinfections(odds ratio[OR]=2.573,95%confidence interval[CI]:1.150-5.757,P=0.0214)and lower CD4^(+)/CD8^(+)T cell ratios(OR=0.048,95%CI:0.005-0.429,P=0.0067).Importantly,patients with higher loads of HCMV and TTV,but not EBV,exhibited worse clinical outcomes.Specifically,patients with HCMV reads per million(RPM)>0 and TTV RPM>5 exhibited significantly higher risks of poor prognosis and intensive care unit(ICU)admission.In contrast,EBV RPM showed no association with clinical outcomes in this context.In conclusion,HCMV and TTV may serve as prognostic biomarkers linked to poorer outcomes in HIV-positive patients.Detection of HCMV and TTV could predict clinical outcomes and improve patient management strategies.展开更多
Parvovirus B19(B19V)infection can cause pure red cell aplasia(PRCA)in patients with human immunodeficiency virus(HIV)infection.Intravenous immunoglobulin(IVIG)is a preferred treatment option.From July 2019 to March 20...Parvovirus B19(B19V)infection can cause pure red cell aplasia(PRCA)in patients with human immunodeficiency virus(HIV)infection.Intravenous immunoglobulin(IVIG)is a preferred treatment option.From July 2019 to March 2022,four patients with HIV infection were admitted to Guangzhou Eighth People’s Hospital with dizziness and fatigue and were diagnosed with PRCA.Blood investigations revealed severe anemia and the B19V genome.Therefore,the four patients were diagnosed with B19V-induced PRCA.All four patients received red blood cell transfusion in the setting of antiretroviral therapy,and two of the four patients received intravenous immunoglobulin(IVIG).After 3-7 months of treatment,all four patients recovered,although two did not receive IVIG.This suggests that IVIG is not always necessary for the treatment of PRCA in patients with HIV infection and that effective antiretroviral therapy and immunological reconstitution play an important role in the eradication of parvovirus.展开更多
基金the Ethics Committee of Guangzhou Eighth People's Hospital(202033166),and all participants provided written informed consent.
文摘Some HIV-infected individuals receiving ART develop low-level viremia(LLV),with a plasma viral load of 50-1000 copies/mL.Persistent low-level viremia is associated with subsequent virologic failure.The peripheral blood CD4^(+)T cell pool is a source of LLV.However,the intrinsic characteristics of CD4^(+)T cells in LLV which may contribute to low-level viremia are largely unknown.We analyzed the transcriptome profiling of peripheral blood CD4^(+)T cells from healthy controls(HC)and HIV-infected patients receiving ART with either virologic sup-pression(VS)or LLV.To identify pathways potentially responding to increasing viral loads from HC to VS and to LLV,KEGG pathways of differentially expressed genes(DEGs)were acquired by comparing VS with HC(VS-HC group)and LLV with VS(LLV-VS group),and overlapped pathways were analyzed.Characterization of DEGs in key overlapping pathways showed that CD4^(+)T cells in LLV expressed higher levels of Th1 signature transcription factors(TBX21),toll-like receptors(TLR-4,-6,-7 and-8),anti-HIV entry chemokines(CCL3 and CCL4),and anti-IL-1βfactors(ILRN and IL1R2)compared to VS.Our results also indicated activation of the NF-κB and TNF signaling pathways that could promote HIV-1 transcription.Finally,we evaluated the effects of 4 and 17 tran-scription factors that were upregulated in the VS-HC and LLV-VS groups,respectively,on HIV-1 promoter activity.Functional studies revealed that CXXC5 significantly increased,while SOX5 markedly suppressed HIV-1 tran-scription.In summary,we found that CD4^(+)T cells in LLV displayed a distinct mRNA profiling compared to that in VS,which promoted HIV-1 replication and r+eactivation of viral latency and may eventually contribute to virologic failure in patients with persistent LLV.CXXC5 and SOX5 may serve as targets for the development of latency-reversing agents.
基金supported by the Key-Area Research and Development Program of Guangdong Province(2022B1111020002)the Science and Technology Project of Guangzhou(2025A03J3818,2024A03J0883,2023A03J0807,and 202201020527)the National Natural Science Foundation of China(92269108).
文摘Opportunistic infections caused by viruses,bacteria,fungi,and parasites,are commonly reported in hospitalized human immunodeficiency virus(HIV)-positive patients,but their detrimental contribution to disease severity remains under explored.In this study,we examined the coinfection profiles of 126 HIV-positive patients with suspected respiratory,bloodstream,or neurological infections.Lower respiratory tract(LRT)samples,cerebrospinal fluid,and blood samples collected within the first seven days of admission were subjected to metagenomic next-generation sequencing(mNGS).Additionally,a multiplex polymerase chain reaction(PCR)detection kit to identify ten commonly known respiratory pathogens was applied to the LRT samples.Of 126 HIV-positive patients,111(88.1%)were coinfected with at least one known virus.Epstein-Barr virus(EBV)(71/111,64.0%),human cytomegalovirus(HCMV)(64/111,57.7%),and torque teno virus(TTV)(63/111,56.8%)were the three most prevalent coinfected viruses.Fungal coinfections(58/126,46.0%)and bacterial coinfections(47/126,37.3%)were less frequent than viral coinfections.Higher viral loads of coinfection were associated with fungal coinfections(odds ratio[OR]=2.573,95%confidence interval[CI]:1.150-5.757,P=0.0214)and lower CD4^(+)/CD8^(+)T cell ratios(OR=0.048,95%CI:0.005-0.429,P=0.0067).Importantly,patients with higher loads of HCMV and TTV,but not EBV,exhibited worse clinical outcomes.Specifically,patients with HCMV reads per million(RPM)>0 and TTV RPM>5 exhibited significantly higher risks of poor prognosis and intensive care unit(ICU)admission.In contrast,EBV RPM showed no association with clinical outcomes in this context.In conclusion,HCMV and TTV may serve as prognostic biomarkers linked to poorer outcomes in HIV-positive patients.Detection of HCMV and TTV could predict clinical outcomes and improve patient management strategies.
基金Guangzhou Basic Research Program on People’s Livelihood Science and Technology(202002020005)National Natural Science Foundation of China(82072265)+1 种基金Technology Planning Project of Guangdong Province(2021B1212040017)Sun Yat-sen University Founded Program(2022_76220_B21127)。
文摘Parvovirus B19(B19V)infection can cause pure red cell aplasia(PRCA)in patients with human immunodeficiency virus(HIV)infection.Intravenous immunoglobulin(IVIG)is a preferred treatment option.From July 2019 to March 2022,four patients with HIV infection were admitted to Guangzhou Eighth People’s Hospital with dizziness and fatigue and were diagnosed with PRCA.Blood investigations revealed severe anemia and the B19V genome.Therefore,the four patients were diagnosed with B19V-induced PRCA.All four patients received red blood cell transfusion in the setting of antiretroviral therapy,and two of the four patients received intravenous immunoglobulin(IVIG).After 3-7 months of treatment,all four patients recovered,although two did not receive IVIG.This suggests that IVIG is not always necessary for the treatment of PRCA in patients with HIV infection and that effective antiretroviral therapy and immunological reconstitution play an important role in the eradication of parvovirus.
