| [Objective]:This study explored the clinical features of acute HIV-infected patients(AHI) during the acute infection and the dynamics of immunological and virological characteristics during 48 weeks of antiretroviral therapy(ART) to improve the understanding of early diagnosis of acute HIV infection. The effects of extracts of a Chinese medical plant (Tripterygium wilfordii Hook F, TwHF)and raltegravir on immune activation and HIV reservoirs were evaluated. Early ART may be a prerequisite to achieving long-term control of viral replication upon ART withdrawal.[Methods]:1. Cross sectional study:Fourty four ART-naive AHI patients were included. The clinical information comes from the infectious department of PUMCH.CD38 and HLA-DR expression on peripheral blood CD8+T cells, CD4+T cell count, CD8+T cell count memory and naive CD4+T cell subsets were measured by flow cytometry. Plasma HIV-RNA was dtermined by with Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test by an ultra-sensitive RT-PCR method.2. Cohort study:This study enrolled 27 AHI patients, and 27 Chronic HIV-infected (CHI) patients exactly matched for CD4+T cell counts constituted the control group. AHI group were dividied into persons who received RAL-containing regimen and Extracts of TwHF(20mg,3 times daily)were added to the background ART after 6 months(+TwHF group), who only received RAL-containing regimen without TwHF (-TwHF group) and who received the standard 3 combination therapy(control group). Patients were followed at baseline, one month after ART initiation and at a 3-month intevals thereafter. We measured CD4/CD8 ratio、CD8+ T-cell activation (percent CD38+/HLA-DR+) and HIV viral load.3. Cohort study:Patients who started ART in acute HIV infection (AHI, n=16) or in chronic infection (CHI, n=16) were studied. AHI goup were dividied into +TwHF group、-TwHF group and control group. We measured HIV reservoir size based on HIV DNA in the peripheral blood mononuclear cell(PBMC) and analyzed the correlation between HIV DNA and CD4/CD8 ratio、CD8+T-cell activation (percent CD38+/HLA-DR+) HIV viral load.[Results]:1. Crosssectional study:Among those 44 patients,37 of the patients presented significant symptoms, including fever (28 cases,63.6%), enlargement of cervical lymph nodes(23 cases,52.3%), skin rashes (8 cases,18.2%), diarrhea (9 cases, 20.5%), sore throat (4 cases,9.1%), and cough (4 cases,9.1%); some symptoms were less frequent, including 1 case of Guillain-Barre syndrome(4%),1 case of upper arm cellulitis (2.3%),1 case of headache and vomiting(2.3%), and 1 case of perianal abscess (2.3%). The duration of infection were 85 (IQR:51,118) days. On the other hand, laboratory examinations revealed 25 cases of elevated peripheral lymphocytes (56.8%),1 case of thrombocytopenia (2.3%), and 2 negative results of HIV antibody (4.5%), which were diagnosed according to two consecutive positive results of plasma viral load. The mean viral load of the patients was 4.68±0.83 1g copies/ml, CD4+ T cell count:413 (IQR:359,620) cells/ul, CD8+ T cell count: 1521 (IQR:1054,2226)cells/ul, the max was 7984/ul, the CD4/CD8 ratio was 0.29(0.15,0.37),42 (95.5%) of the patients has obvious inversion, HLA-DR and CD38 expression on CD8+T cells is 74.4%±.2% and 84.7%±12.5% correspondingly; the viral load has positive correlation with the expression of HLA-DR and CD38(r=0.43, p=0.005; r=0.50, p=0.0008). Negative correlation was found between CD38 expression on CD8+T cells and CD4 count. No correlation was found between CD8+T cell immune activaton and duration of infection.2. Cohort study:In the AHI and CHI group, the median degradation value of viral load was 3.68 and 3.02 log10copies/ml from baseline to week 48,CD4 counts steadily increased over the course of treatment. The median variation of CD4 count were 223/ul and 121/ul, respectively (p=0.032), The median variation of CD8 count were 1102/ul and 271/ul (p=0.004). early ART in AHI group predicted lower on-therapy CD8+T-cell activation than CHI group (P=0.006), no significant difference on CD4/CD8 ratio and the expression of HLA-DR on CD8+T cells were seen. During the first year of the suppressive ART, A significant decay of HIV-1 viral load was observed after intensification in the 21 patients(p=0.019), included the median variation of CD4 count were 151/ul、227/ul、193/ul (p=0.57), the median variation of CD8 count were 1527/ul、1112/ul 1550/ul(p=0.74), no differences on CD8+T cell activation were found among+TwHF group、-TwHF group and control group (p>0.05).3. Cohort study:HIV DNA level of the AHI and CHI group were 2.11 [1.81,2.45] and 2.22 [2.05,2.54] log10/106PBMC (p=0.57) at baseline, HIV DNA level in PBMC were positively correlated with HIV viral load(p=0.026, r=0.55) in the CHI group, no differences were found in the AHI group. At the end of the follow-up, HIV-DNA levels of PBMC significantly decreased in both AHI patients and CHI patients, no significant difference on the decrease in HIV DNA level between baseline and W24 in AHI patients compared with CHI patients. No differences were found in HIV DNA level among+TwHF group、-TwHF group and control group.[Conclusion]:The most common symptoms of acute HIV infection were fever, enlargement of cervical lymph nodes, skin rashes and diarrhea, elevated peripheral lymphocytes, significant elevation of CD8+ T cell counting and CD4/CD8 ratio inversion, abnormal immune activation can be detected. Viral load and T cell subgroup detection, especially the inversion of CD4/CD8 ratio help diagnosis of acute HIV infection. Compare to the CHI group, ART initiation <6 months after infection is associated with lower levels of T-cell activation, these results extend the previously reported early benefit of raltegravir intensification on the decline of plasma viraemia to treatment-naive patients. HIV persistence is established early in acute HIV infection, ART during AHI or CHI can significantly decrease the HIV DNA, There was a decay in HIV DNA for patients receiving raltegravir and TwHF. |
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