PNEUMOCYSTIS pneumonia (PCP) is among the most common opportunistic infections in patients with acquired immune deficiency syndrome (AIDS).Although trimethoprim-sulfamethoxazole (TMP-SMX) is the first line therapy for...PNEUMOCYSTIS pneumonia (PCP) is among the most common opportunistic infections in patients with acquired immune deficiency syndrome (AIDS).Although trimethoprim-sulfamethoxazole (TMP-SMX) is the first line therapy for that condition given its efficacy,approximately one third of patients experienced dose-limiting toxicity.1 For cases of severe to moderate PCP,if TMP-SMX treatment fails or is contraindicated,primaquine combined with clindamycin or intravenous pentamidine is recommended as second line therapy.2 However,both primaquine and pentamidine are associated with severe adverse reactions and often unavailable at hospitals in China.3 As a result,other treatment options have been explored.展开更多
Objective To investigate the response on late stage Chinese AIDS patients after highly active antiretroviral therapy （HAART）. Methods From October 2002 to March 2004, 20 cases of late stage Chinese AIDS patients we...Objective To investigate the response on late stage Chinese AIDS patients after highly active antiretroviral therapy （HAART）. Methods From October 2002 to March 2004, 20 cases of late stage Chinese AIDS patients were selected to participate in this opened and randomised study, we purposely chose those with CD4＋ T cell counts 〈 100/mm^3. All of them had one or two opportunistic infections and none had been treated with anti-HIV drugs. All patients were tested with CD4＋ （naive CD4＋ T cell defined by CD45RA＋ and CD62L＋, memory CD4＋ T cell defined by CD45RA-）, CD8＋ T cell, plasma HIV viral load, and clinical manifestations on before, during, and after HAART （5 different regimes） on 1, 3, 6, 9, and 12 months. Before HAART mean CD4＋ T cell counts were 32 ± 31 （range 2-91）/mm^3, and plasma HIV viral load were 5.07 ± 0.85（range 2.04-5.70） log copies/mL. In 1 month＇s time patients treated with HAAT had mean CD4＋ and CD8＋ T cell counts increasing rapidly. After 1 month the increasing speed turned to slow down, but HIV viral load decreased predominantly within the first 3 months. The major part of increasing CD4＋ T cells were memory CD4＋ T cells, as for naive CD4＋ T cells increasing low and slow. Clinical symptoms and signs improved, and opportunistic infections reduced. The quality of life will be far much better than before. Each patient was followed for 12 months, and had finished 12 months＇ HAAT. Conclusion This is the first report in China that late stage Chinese AIDS patients after HAART could have their immune reconstitution. The regular pattern is similar to what had been reported in Western countries and also in China. So it is worth to treat late stage Chinese AIDS patients with HAAT.展开更多
Background: Mucosal-associated invariant T(MAIT) cells are systemically depleted in human immunodeficiency virus type 1(HIV-1) infected patients and are not replenished even after successful combined antiretroviral th...Background: Mucosal-associated invariant T(MAIT) cells are systemically depleted in human immunodeficiency virus type 1(HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy(cART).This study aimed to identify the mechanism underlying MAIT cell depletion.Methods: In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.Results: Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4+ T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D(GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory cytokines interleukin-12(IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro.Conclusions: Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients,which could potentiate disease progression and poor immune reconstitution.展开更多
文摘PNEUMOCYSTIS pneumonia (PCP) is among the most common opportunistic infections in patients with acquired immune deficiency syndrome (AIDS).Although trimethoprim-sulfamethoxazole (TMP-SMX) is the first line therapy for that condition given its efficacy,approximately one third of patients experienced dose-limiting toxicity.1 For cases of severe to moderate PCP,if TMP-SMX treatment fails or is contraindicated,primaquine combined with clindamycin or intravenous pentamidine is recommended as second line therapy.2 However,both primaquine and pentamidine are associated with severe adverse reactions and often unavailable at hospitals in China.3 As a result,other treatment options have been explored.
文摘Objective To investigate the response on late stage Chinese AIDS patients after highly active antiretroviral therapy （HAART）. Methods From October 2002 to March 2004, 20 cases of late stage Chinese AIDS patients were selected to participate in this opened and randomised study, we purposely chose those with CD4＋ T cell counts 〈 100/mm^3. All of them had one or two opportunistic infections and none had been treated with anti-HIV drugs. All patients were tested with CD4＋ （naive CD4＋ T cell defined by CD45RA＋ and CD62L＋, memory CD4＋ T cell defined by CD45RA-）, CD8＋ T cell, plasma HIV viral load, and clinical manifestations on before, during, and after HAART （5 different regimes） on 1, 3, 6, 9, and 12 months. Before HAART mean CD4＋ T cell counts were 32 ± 31 （range 2-91）/mm^3, and plasma HIV viral load were 5.07 ± 0.85（range 2.04-5.70） log copies/mL. In 1 month＇s time patients treated with HAAT had mean CD4＋ and CD8＋ T cell counts increasing rapidly. After 1 month the increasing speed turned to slow down, but HIV viral load decreased predominantly within the first 3 months. The major part of increasing CD4＋ T cells were memory CD4＋ T cells, as for naive CD4＋ T cells increasing low and slow. Clinical symptoms and signs improved, and opportunistic infections reduced. The quality of life will be far much better than before. Each patient was followed for 12 months, and had finished 12 months＇ HAAT. Conclusion This is the first report in China that late stage Chinese AIDS patients after HAART could have their immune reconstitution. The regular pattern is similar to what had been reported in Western countries and also in China. So it is worth to treat late stage Chinese AIDS patients with HAAT.
基金supported by the Peking University Clinical Scientist Program Special(BMU2019LCKXJ013)the National Natural Science Foundation Innovation Research Group Project(81721002)+2 种基金the Sanming Project of Medicine Project in Shenzhen(SZSM201612014)the Yunnan Applied Basic Research Projects-Union Foundation by Yunnan Provincial Department of Science and Technology and Kunming Medical University(202001AY070001-154)the Scientific Research Fund of Education Department of Yunnan Province(2021J0297)。
文摘Background: Mucosal-associated invariant T(MAIT) cells are systemically depleted in human immunodeficiency virus type 1(HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy(cART).This study aimed to identify the mechanism underlying MAIT cell depletion.Methods: In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.Results: Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4+ T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D(GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory cytokines interleukin-12(IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro.Conclusions: Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients,which could potentiate disease progression and poor immune reconstitution.
