Impact of SARS-CoV-2 vaccination on systemic immune responses in people living with HIV

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and an ongoing global pandemic. Despite the development of vaccines, which protect healthy people from severe and life-threatening COVID-19, the immunological responses of people with secondary immunodeficiencies to SARS-CoV-2 mRNA vaccines are currently not well understood. Human Immunodeficiency Virus (HIV), causing acquired immunodeficiency syndrome (AIDS), targets CD4+ T helper (Th) cells that orchestrate the immune response. Anti-retroviral therapy suppresses HIV burden and restores Th cell numbers. Here, we investigated the humoral and cellular immune responses elicited by the BTN162b2 vaccine in a cohort of people living with HIV (PLWH), who receive anti-retroviral therapy. While antibody responses in PLWH increased progressively after the first and second vaccination compared to baseline, they were reduced compared to HIV negative study participants (controls). CD8+ T cells exhibited a general activated phenotype and increased effector and effector memory compartments. In contrast, CD4+ Th cell responses exhibited a vaccination-dependent increase and were comparable between PLWH and controls. In line with their reduced humoral response, the correlation between neutralizing antibodies and the CD4+ T cell response was decreased in PLWH compared to healthy controls. Interestingly, CD4+ T cell activation negatively correlated with the CD4 to CD8 ratio, indicating that low CD4 T cell numbers do not necessarily interfere with cellular immune responses. Taken together, our data demonstrate that COVID-19 mRNA vaccination in PLWH results in potent cellular immune responses, but the reduced antibody responses suggest that booster vaccination might be required for preventing disease.

[Effect of long-term highly active antiretroviral therapy on abnormal immune activation and immune reconstruction in HIV-1 infected individuals].

OBJECTIVE: To investigate the effect of long-term highly active antiretroviral therapy (HAART) on the abnormal activation state and immune reconstitution in HIV-1 infected individuals. METHODS: CD4(+)T, CD8(+)T, CD8(+) CD38(+)T, CD8(+)HLADR(+)T and NK cell counts in the peripheral blood of 55 cases of HIV-1 infected individuals were measured by flow cytometry before and after HAART, and 30 healthy individuals served as controls. RESULT: Compared to healthy individuals, the CD4(+)T and NK cells decreased (P < 0.05) and CD8(+)T and CD8(+)HLADR(+)T cells increased significantly (P < 0.05) in HIV-1 infected individuals before HAART. After HAART, CD4(+)T and NK cells were recovered (P < 0.05), but still lower than normal (P < 0.05); CD4(+)T cell count in HIV-1 infected individuals remained stable at 1, 3 and 5 years after treatment, there were no significant differences among each groups; NK cell count had a downward trend with HAART (P < 0.05), there were statistical differences between 1-year and 5-year-HAART groups(P < 0.05). CD8(+)HLADR(+)T cells decreased promptly (P < 0.05), there were statistical differences between before and after HAART groups, 1-year and 5-year, 3-year and 5-year HAART groups (P < 0.05). CD8(+)CD38(+)T cells declined slowly, with no statistical differences amont each groups. CONCLUSION: HAART can effectively reduce abnormal immune activation in HIV-1 infected individuals and achieve immune reconstitution to a certain degree.

[Impact of highly active antiretroviral therapy on plasma MCP-1 and MSP in AIDS patients].

OBJECTIVE: To study the effect of highly active antiretroviral therapy (HAART) on plasma levels of MSP and MCP-1 in AIDS patients. METHODS: Forty Chinese AIDS patients were treated with HAART for 3 months and 84 German AIDS patients with HAART for 3 to 6 years. The pre-treatment and post-treatment plasma levels of MSP and MCP-1 were measured by enzyme-linked immunosorbent assay (ELISA), and their correlations with CD4+ cell counts and viral loads were analyzed. RESULT: The mean levels of MCP-1 were significantly higher and MSP were significantly lower in HIV-infected patients compared with the HIV-negative controls (P <0.01). After HAART for three months, there were no significant changes in the levels of these cytokines. But after long-term HAART (for 3 to 6 y), the level of MCP-1 was increased and that of MSP decreased significantly (P<0.01). There was a negative correlation between MSP and MCP-1 levels, and the same for MSP level and CD4+ cell counts; while there was a positive correlation between MCP-1 levels and CD4+ cell counts. CONCLUSION: The changed plasma levels of MSP and MCP-1 are associated with HIV-1 infection and HAART may reverse the levels of these two cytokines.

Sequence detection of HBV-DNA P and C region in HIV/HBV superinfection subjects with drug resistance to HAART / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To further study the resistance of HBV to high activity antiretrovirus therapy(HAART).</p><p><b>METHODS</b>HBV-DNA was quantitatively detected by real-time PCR in 36 HIV/HBV superinfection subjects, C region and P region HBV-DNA in high copies HBV-DNA subjects were detected by routine PCR, PCR products were purified and sequenced and compared with the HBV international Genbank using BLSAT softy ware.</p><p><b>RESULT</b>HBV-DNA was positive in 4 of 36 patients (11.1%) and another 3 had low copies(<10(4)copies/ml), one had a high HBV-DNA copies (10(7)copies/ml). It's HBV-DNA C region sequence had mutation on 2 sites (nt 2412 T/C; nt 2413 T/C) and 1 mutation P region (nt 741 A/G, also YMDD/YVDD) compared with HBV international Genbak reference sequence.</p><p><b>CONCLUSION</b>The HBV resistance to HAART may be related with multiple genetic mutations in the C and P regain of HBV-DNA.</p>

Effect of HIV-1 infection on apoptosis of CD4+ T lymphocytes mediated by Fas / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the pathogenic role of Fas/CD95 in HIV-1 infection subjects, and to investigate the effects of HIV on plasma levels of sFas and the expression of CD95 on different CD4(+) T lymphocyte subpopulations.</p><p><b>METHODS</b>Four-color flow cytometry was used to determine the expression of CD95, CD45RO, CD45RA on CD4(+ )T lymphocyte in peripheral blood from HIV-1 infection subjects and serum Fas levels were quantified by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULT</b>Compared with healthy controls, serum Fas levels were significantly increased (P<0.05) in HIV group and positively correlated with the disease progress. The expression of CD95 on naive T-lymphocyte subsets was increased whereas that on memory T-lymphocyte subsets was decreased.</p><p><b>CONCLUSION</b>Fas plays an important role in the deletion of CD4(+) T-lymphocyte during HIV-1 infection. Further understanding of the relationship between Fas/CD95 and CD45RO/CD45RA may help to predict the progression of the disease and the clinical outcome.</p>

Evaluation of serum interleukin-18 and interleukin-10 in patients with HIV-1 and hepatitis viruses co-infected subjects / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the significance of cytokines in patients with HIV and hepatitis viruses co-infection.</p><p><b>METHODS</b>Serum levels of IL-18 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). HIV-RNA levels were measured in EDTA plasma by quantitative reverse polymerase chain reaction (PCR). CD4(+) lymphocyte counts were determined by four-color Flow cytometry (FCM).</p><p><b>RESULTS</b>The levels of IL-18 were significantly higher in HIV-infected persons compared with those in controls (P<0.05). With HIV disease progression, IL-18 levels increased while Il-10 levels decreased. HCV patients showed lower levels of IL-18 and IL-10 than those of the co-infection group.</p><p><b>CONCLUSION</b>Univariate analyses shows significant co-variables IL-10 in co-infection. Up-regulating IL-18 activity and/or down-regulating IL-10 may be a potential therapy to patients with HIV and hepatitis viruses co-infection.</p>

Expression of co-receptor on different T lymphocytes subpopulations after effective HAART / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To measure CCR5 and CXCR4 chemokine receptor expression on CD4 and CD8 T cells in HIV-1 infection and to relate levels to the distribution of CD45RO memory and CD45RA-naive subsets after effective HAART.</p><p><b>METHODS</b>Four-color cytofluorometry with appropriate conjugated monoclonal antibodies (mAbs) was performed to define CD45RA and CD45RO subsets of CD4 and CD8 T cells and measure the expression of CCR5, CXCR4 in blood from 43 received HAART patients and 5 non-treated HIV and 13 healthy controls.</p><p><b>RESULTS</b>The levels of CCR5 and CXCR4 on CD4 and CD8 T cells and their CD45RO/CD45RA subsets in HIV-1-infected patients had not any statistical significance than that on control subjects and effective HAART could adjust the expression on T cells.</p><p><b>CONCLUSION</b>CXCR4/CCR5 plays an important role in the progress of HIV-1 infection. The most favorable condition for treatment should be initiated before stage B.</p>

Immune activation in AIDS related Kaposi's sarcoma / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the pathogenesis role of immune system activation in AIDS related Kaposi's sarcoma(AIDS-KS).</p><p><b>METHODS</b>The serum levels of sFas, beta 2-microglobin, IL-10, IL-16, IL-18, IL-6 and sIL-4R were detected by ELISA in 8 AIDS-KS patients, 28 patients with HIV infection but without Kaposi's sarcoma(HIV-NKS) and 16 normal controls. The lymphocyte and their subsets, CD38(+) CD8, HLA-DR(+)CD8 in the peripheral blood mononuclear cell (PBMCs) in 12 AIDS-KS and 32 HIV-NKS were detected by flow cytometer.</p><p><b>RESULTS</b>Beta 2-MG and sIL-4R in HIV-NKS were significantly higher than those in normal controls(P<0.05), IL-16 in HIV-NKS was significantly lower than that in controls(P<0.05). IL-18 was higher in both AIDS-KS and HIV-NKS compared with normal controls. In AIDS-KS, CD3, CD4, CD8, NK and HLA-DR(+)CD8 were lower than those in HIV-NKS whereas CD19 and CD38(+)CD8 were higher than those in HIV-NKS. But the difference was not statistically(P<0.05).</p><p><b>CONCLUSION</b>Although both AIDS-KS and HIV-NKS demonstrate some activation of immune system, there appears to be no significant difference between immune responses in KS and NKS patients. These data suggest that the activation of the immune system is unlikely to contribute significantly to the pathogenesis of AIDS-KS.</p>

Drug resistance of HIV-infected patients after the failure of highly active antiretroviral treatment / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To find out the mechanism of drug resistance by detecting the mutations of HIV RNA in patients who failed in the anti-HIV therapy, to direct the clinical use of anti-HIV drugs and to complement the existing drug resistant database.</p><p><b>METHODS</b>HIV RNA and DNA were extracted from the plasma of 10 HIV-infected patients who developed drug resistance in the Clinic of AIDS, Ruhr University, Bochum, Germany. Then HIV-RNA was amplified in the reverse transcriptase (RT) and protease regions by polymerase chain reaction (PCR). After purified, the PCR products was sequenced. The acquired sequences were compared with the international standard strain HXB2CG and the resistant database of Stanford University.</p><p><b>RESULTS</b>Some mutations were found to cause the corresponding resistance to certain drugs and were consistent with the clinical results. Some mutations existed in some patients, such as V179I in RT and K20T, K20I in protease, which hadn't been reported in the resistant database of Stanford University yet.</p><p><b>CONCLUSION</b>Patients who fail in HAART have different mutations in RT and protease regions. Mutations such as V179I in RT and K20T, K20I etc in protease may be related to drug resistance.</p>