| Objectives:1. To analyze the CD4+T cell count before and after treatment of TwHF, as well as the functional, naive and memory subsets of CD4+T cell. To evaluate the effect of TwHF in immune reconstitution in INRs.2. To analyze the activation subset of T cells before and after treatment of TwHF, and to determine if TwHF can inhibit IA in INRs.3. To analyze the Treg subset of T cells before and after treatment of TwHF, and to determine if TwHF can increase the proportion of Treg in INRs.4. To analyze the expression of TLR4after stimulation by LPS in the PBMC of the patients, and to determine if TwHF can reduce IA mediated by the LPS/TLR4pathway.Methods:Eighteen patients receiving cART with undecteble plasma HIV-RNA for at least18months and suboptimal CD4cell recovery were enrolled. Immune nonresponders (INR, n=9) were defined as patients with CD4cell count<200cells/μL while inadequate responders (InaR, n=9) were defined as patients with CD4count between200and300cells/μL. TwHF extract was added to their backgrougnd ART at a dosage of10mg three times daily for12months. They were followed from baseline to month3,6,9,12, and15. Peripheral T lymphocyte subsets were measured, including CD4+T cell, CD4+CD28+functional subset, naive and memory CD4+T cell subsets. PBMC was collected and stimulated by LPS, followed by the measurement of TLR4expression. CD4+CD25high Treg subset was also measured. All the T cell subsets were measured by flow cytometry. Datas were statistically analyzed. A P-value of<0.05was considered significant.Results:1. The effect of TwHF on the T cell subsets in INRs and InaRsFor INRs and InaRs, TwHF increased the CD4+T cell count, from187±62/μl to291±61/μl, P<0.0001. The increase in CD4+T cell count was mainly due to the recovery memory CD4+T cell (from134±40/μl to233±70/μl, P=0.0001), instead of naive CD4+T cell (from41±30/μl to51±49/μl, P=0.027). The patients showed higher rate of the CD4+T cell increase after treatment of TwHF (the slope of CD4+T cell vs time increased from2.902+1.733to5.959+3.106, P=0.0013). Besides, the functional subset of CD4+CD28+T cell count also increased from166±60/μl to281±54/μl, P<0.0001).2. The effect of TwHF on the activation T cell subsets in INRs and InaRsAfter nine months of treatment by TwHF with cART, the proportion of activation T cell subsets was generally reduced. Proportion of CD4+HLA-DR+CD38-/CD4+changed from (34.8±9.9)%to (39.8±12.7)%, P=0.0766; proportion of CD4+HLA-DR-CD38+/CD4+decreased from (21.5±11.0)%to (12.8±5.2)%, P=0.0006; CD4+HLA-DR+CD38+/CD4+from (14.8±7.6)%to (8.9±3.4)%, P=0.0156; CD8+HLA-DR+CD38-/CD8+from (28.2±11.2)%to (25.0±15.4)%. P=0.4606; CD8+HLA-DR-CD38+/CD8+from (8.1±5.9)%to (2.8+4.1)%, P=0.0020; CD8+HLA-DR+CD38+/CD8+from (10.9±7.5)%to (4.6±4.0)%, P=0.0055. Subsets of HLA-DR-CD38+decreased more significantly than subsets of HLA-DR+CD38+; activation subset of INRs decreased more significantly than that of InaRs. TwHF had no significant effect on the HLA-DR+CD38-subsets. Proportion of CD4+HLA-DR-CD38+, CD4+HLA-DR+CD38+and CD8+HLA-DR-CD38+showed a negative correlation with the CD4+T cell count (P=0.01319, r2=0.03806; P=0.0160, r=0.09440; P=0.0399, r2=0.06964, respectively).3. The effect of TwHF on Treg in INRs and InaRsTreatment of TwHF did not show a significant effect on CD4+CD25high Treg proportion in INRs and InaRs (P<0.05).4. The effect of TwHF on the expression of TLR4stimulated by LPS in PBMC of INRs and InaRsTreatment of TwHF did not show a significant effect on the expression of TLR4upon LPS stimulation in INRs and InaRs (P<0.05).Conclusion:1. In INRs and InaRs, TwHF increased the CD4+T cell count. The increase of CD4+T cell count is mainly attributed to the reovery of memory CD4+T cell. The CD4+T cells inceased were mainly functional sebset of CD4+CD28+T cells.2. Generally, treatment of TwHF can reduce the proportions of activated T cell subsets.3. The effect of TwHF in this study may not be achieved by increasing the proportion of Treg or inhibiting the LPS-TLR4pathway. |
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