Decreasing CD4+ T-cell count during suppressed or low-level viraemia in patients with HIV infection

BACKGROUND: Suboptimal improvement in CD4+ T-cell count is not uncommon in HIV-infected patients with suppressed plasma HIV RNA levels, and a decrease in CD4+ T-cell count in patients with suppressed or low-level viraemia has been observed. METHODS: Our objectives were to identify the prevalence of decreasing CD4+ T-cell counts during suppressed or low-level viraemia, to determine the frequency of clinical events during and immediately after such decreases, and to examine for associations with individual variables. A matched case-control study was undertaken using the Duke Infectious Diseases Clinic database (n = 3,949). Cases had at least two consecutive significant decreases in either CD4+ absolute count or CD4+ percentage, while also having plasma HIV RNA levels < 1,000 copies/ml. RESULTS: The prevalence of decreasing CD4+ T-cell counts during suppressed or low-level viraemia was 1.22%. Only three HIV-associated clinical events occurred. The majority of cases had an increase in the CD4+ T-cell count immediately following the study period. The use of either zidovudine or stavudine was weakly associated with decreasing CD4+ T-cell counts in a multivariable analysis, but this association was not present in cases with only a decrease in CD4+ T-cell percentage. CONCLUSIONS: Decreasing CD4+ T-cell counts during suppressed or low-level viraemia are rare, typically transient, and not associated with an increase in HIV-associated clinical events.     

Virological and immunological effects of antioxidant treatment in patients with HIV infection

BACKGROUND: Intracellular oxidative stress in CD4+ lymphocytes due to disturbed glutathione homeostasis may lead to impaired lymphocyte functions and enhanced HIV replication in patients with HIV infection, especially in those with advanced immunodeficiency. The aim of the present study was to assess whether short-term, high-dose antioxidant treatment might have effects on immunological and virological parameters in patients with HIV infection. MATERIALS AND METHODS: In this pilot study, we examined virological and immunological effects of antioxidant combination treatment for 6 days with high doses of N-acetylcysteine (NAC) and vitamin C in 8 patients with HIV infection. The following were assayed before, during and after antioxidant treatment: HIV RNA plasma levels; numbers of CD4+, CD8+, and CD14+ leukocytes in blood; plasma thiols; intracellular glutathione redox status in CD4+ lymphocytes and CD14+ monocytes; lymphocyte proliferation; lymphocyte apoptosis and plasma levels of tumour necrosis factor (TNF)alpha; soluble TNF receptors and neopterin in plasma. RESULTS: No significant changes in HIV RNA plasma levels or CD4+ lymphocyte counts in blood were noted during antioxidant treatment in the patient group. However, in the 5 patients with the most advanced immunodeficiency (CD4+ lymphocyte counts < 200 x 106 L(-1)), a significant rise in CD4+ lymphocyte count, a reduction in HIV RNA plasma level of 0.8 log, an enhanced lymphocyte proliferation and an increased level of intracellular glutathione in CD4+ lymphocytes were found. No change in lymphocyte apoptosis was noted. CONCLUSIONS: Short-term, high-dose combination treatment with NAC and vitamin C in patients with HIV infection and advanced immunodeficiency lead to immunological and virological effects that might be of therapeutic value.     

HIV/TB并发感染患者外周血 T淋巴细胞表达及与 HIV RNA载量的相关性研究

目的　探讨人类免疫缺陷病毒 /结核病（ human immunide.ciency virus/tuberculosis,HIV/TB）并发感染患者的外周血 T淋巴细胞亚群的表达及其与 HIV RNA载量的相关性。方法　选取 2018年 6月～ 2020年 6月在南京市公共卫生医疗中心就诊的 HIV/TB并发感染患者 38例作为 HIV/TB组,另选取单纯人类免疫缺陷病毒 /获得性免疫缺陷综合征（human immunode.ciency virus/acquired immune de.ciency syndrome,HIV/AIDS）39例作为 HIV组,单纯 TB患者 35例作为 TB组,体检健康者 35例作为健康对照组。流式细胞术检测各组 CD3+,CD4+,CD8+ T细胞计数和 CD4+/CD8+比值;荧光定量 PCR检测 HIV RNA载量。采用 SPSS17.0统计学软件进行统计分析,并进行 Spearman相关系数分析。结果　CD3+,CD4+和 CD8+ T细胞数, CD4+/CD8+比值在各组中的差异均具有统计学意义（ H=40.758,104.279,9.637和 101.770,均 P＜ 0.05）,组间两两比较结果表明,与健康对照组相比, TB组 CD3+和 CD8+T细胞数明显降低,差异均有统计学意义（ Z=-2.520,-2.972,P=0.012,0.003）;HIV组和 HIV/TB组 CD3+,CD4+ T细胞数以及 CD4+/CD8+比值均明显降低（ Z=-7.391~-4.325,均 P=0.000）。与 TB组相比, HIV组 CD3+, CD4+ T细胞数和 CD4+/CD8+比值均明显降低,差异均有统计学意义（ Z=-2.138,-7.032和 -7.380,P=0.032,0000和 0.003）,但 CD8+ T细胞数明显升高（Z=-2.463,P=0.014）;而 HIV/TB组 CD3+和 CD4+ T细胞数以及 CD4+/CD8+比值均明显降低,差异均有统计学意义（Z=-3.865,-6.907和 -6.759,均 P=0.000）。与 HIV组相比, HIV/TB组的各项流式指标及 HIV RNA载量差异均无统计学意义（均 P >0.05）。HIV RNA载量与 CD3+,CD4+,CD8+ T细胞数以及 CD4+/CD8+比值均呈显著负相关（ r分别为 -0.327,-0.370,-0.296和 -0.327,均 P <0.05）。结论　HIV/TB并发感染患者外周血 CD3+,CD4+ T细胞数和 CD4+/CD8+比值均明显降低。无论有无并发 TB感染,HIV感染者的细胞免疫功能均随着病毒载量的升高而显著降低。     

Homeopathy in HIV infection: a trial report of double-blind placebo controlled study.

OBJECTIVE: This study was aimed to evaluate the immuno-modulator role of homeopathic remedies in Human Immunodeficiency Virus (HIV) infection. METHODOLOGY: A randomised double blind clinical trial was conducted to compare the effect of homeopathic remedies with placebo, on CD4+ve T-lymphocytes in HIV infected individuals, conforming to Centres for Disease Control (CDC) stage II & III. 100 HIV+ve individuals between 18-50 y (71% males) were included in the study. 50 cases conformed to CDC stage II--Asymptomatic HIV infection, and 50 cases to CDC stage III--Persistent Generalised Lymphadenopathy (PGL). Cases were stratified according to their clinical status and CD4+ve lymphocyte counts. The randomisation charts were prepared much before the start of the trial by randomly assigning placebo and verum codes to registration numbers from 1 to 50. A single individualised homeopathic remedy was prescribed in each case and was followed up at intervals of 15 d to one month. A six months study was performed for each registered case. Assessment of progress was made by evaluation of CD+ve lymphocyte counts, which was the prospectively-defined main outcome measure of the study; the results were compared with the base line immune status. RESULTS: In PGL, a statistically significant difference was observed in CD+ve T-lymphocyte counts between pre and post trial levels in verum group (P < 0.01). In the placebo group a similar comparison yielded non-significant results. (P = 0.91). Analysis of change in the pre and post trial counts of CD4+ve cells between groups was also statistically significant (P = 0.04). In asymptomatic HIV infection, differences in absolute CD4+ve lymphocyte counts between pre and post trial levels were not significant. Analysis of changes in pre and post trial CD4 levels of placebo and verum groups for combined strata of asymptomatic and PGL groups was also not significant. CONCLUSION: The study suggests a possible role of homeopathic treatment in HIV infection in symptomatic phase, as evidenced by a statistically significant elevation of base line immune status in persistent generalised lymphadenopathy.     

Low current and nadir CD4+ T-cell counts are associated with higher hepatitis C virus RNA levels in the Swiss HIV cohort study

BACKGROUND: The aim of this study was to evaluate the effect of CD4+ T-cell counts and other characteristics of HIV-infected individuals on hepatitis C virus (HCV) RNA levels. METHODS: All HIV-HCV-coinfected Swiss HIV Cohort Study participants with available HCV RNA levels and concurrent CD4+ T-cell counts before starting HCV therapy were included. Potential predictors of HCV RNA levels were assessed by multivariate censored linear regression models that adjust for censored values. RESULTS: The study included 1,031 individuals. Low current and nadir CD4+ T-cell counts were significantly associated with higher HCV RNA levels (P = 0.004 and 0.001, respectively). In individuals with current CD4+ T-cell counts < 200/microl, median HCV RNA levels (6.22 log10 IU/ml) were +0.14 and +0.24 log10 IU/ml higher than those with CD4+ T-cell counts of 200-500/microl and > 500/microl. Based on nadir CD4+ T-cell counts, median HCV RNA levels (6.12 log10 IU/ml) in individuals with < 200/microl CD4+ T-cells were +0.06 and +0.44 log10 IU/ml higher than those with nadir T-cell counts of 200-500/microl and > 500/microl. Median HCV RNA levels were also significantly associated with HCV genotype: lower values were associated with genotype 4 and higher values with genotype 2, as compared with genotype 1. Additional significant predictors of lower HCV RNA levels were female gender and HIV transmission through male homosexual contacts. In multivariate analyses, only CD4+ T-cell counts and HCV genotype remained significant predictors of HCV RNA levels. Conclusions: Higher HCV RNA levels were associated with CD4+ T-cell depletion. This finding is in line with the crucial role of CD4+ T-cells in the control of HCV infection.     

Analysis of telomere length and thymic output in fast and slow/non-progressors with HIV infection.

There are two models for CD4+ T-cell depletion leading to AIDS: a kinetic model and an immune suppression model. In the kinetic model, direct cell killing due to viral replication results in a continuous demand for CD4+ T-cells, which eventually exhausts their capacity for renewal by proliferative mechanisms. In the immune suppression model, CD4+ T-cell decline is due to an indirect global inhibitory effect of the virus on uninfected immune cell function. In order to address differences in the two models, we investigated proliferative history and thymic output in PBMC from the GRIV cohort of fast (FP) and slow/non-progressors (S/NP), and uninfected controls. Proliferative history and thymic output were assessed by measurement of mean telomeric restriction fragment (TRF) length and T-cell receptor Rearrangement Excision Circles (TREC) levels, respectively. Mean TRF lengths were significantly shorter in S/NP (n = 93, 7.59 +/- 0.11 kb) and FP (n = 42, 7.25 +/- 0.15 kb) compared to controls (n = 35, 9.17 +/- 0.19 kb). Mean TRF length in PBMC (n = 9, 7.32 +/- 0.31 kb) and CD4+ enriched fractions (n = 9, 7.41 +/- 0.30 kb) from a subset of non-GRIV HIV-1 infected samples were also significantly smaller than PBMC (n = 8, 9.77 +/- 0.33 kb) and CD4+ fractions (n = 8, 9.41 +/- 0.32 kb) from uninfected controls. Rates of telomeric shortening, however, were similar among S/NP (n = 93, -45 +/- 20 bp/yr), FP (n = 42, -41 +/- 14 bp/yr) and controls (-29 +/- 17 bp/yr). Paralleling differences observed in mean TRF length, TREC levels were significantly reduced in S/NP (n = 10, 3,433 +/- 843 mol/mu and FP (n = 8, 1,193 +/- 413) compared to controls (n = 15, 22,706 +/- 5,089), indicative of a defect in thymopoiesis in HIV-1 infection. When evaluated in the context of reduced thymopoiesis, the difference in mean TRF length between S/NP and controls (1.58 +/- 0.30 kb) is similar to that observed between memory and na?ve T-cells (1.4 +/- 0.1 kb), and may reflect perturbations in the peripheral T-cell population due to a decline in thymic output of na?ve T-cells rather than increased turnover. Based on the different clinical criteria used to select S/NP and FP, the sight difference in TREC between these two groups suggests the threshold for pathogenesis as a result of na?ve T-cell depletion may be quite low, and incremental increases in thymic output may yield substantial clinical results. Future studies regarding therapeutic vaccination, specifically with HIV-1 Tat targeted anti-immunosuppressive vaccines, should address the defect in thymic output in HIV-1 infection by using TREC analysis as a rapid method for biological evaluation.     

Influence of 4- and 6-color flow cytometers and acquisition/analysis softwares on the determination of lymphocyte subsets in HIV infection

BACKGROUND AND OBJECTIVES: Lymphocyte immunophenotyping provides valuable information for the diagnosis and monitoring of patients with cellular immunodeficiencies, such as HIV/AIDS. In this study, we have assessed the influence of 4-color and 6-color flow cytometers, and respective analytical softwares on the enumeration of lymphocytes in HIV infected individuals. METHODS: The expression of various cell surface markers on lymphocytes was measured from the EDTA blood of 66 HIV infected patients on the FACSCalibur (4-color) and FACSCanto (6-color) flow cytometers. Percentage of lymphocytes expressing a particular cell surface marker was analyzed on FACSCalibur using the Cell Quest Pro software (v 5.2), while the analysis on FACSCanto was done using FACSCanto (v 1.0.3) and FACSDiva (v 4.1) softwares respectively. RESULTS: The data shows significantly higher mean CD3 T-cell counts on FACSCalibur, Cell Quest Pro (1,864 +/- 1,044 cells/microl) as compared to FACSCanto (1,840 +/- 1,040 cells/microl) (P < 0.05). The CD4 T-cell counts were also higher on FACSCalibur, Cell Quest Pro (885 +/- 770 cells/microl), and FACSDiva (892 +/- 773 cells/microl) versus FACSCanto (867 +/- 767 cells/microl) (P < 0.05). FACSCalibur, Cell Quest Pro, and FACSDiva showed similar values except for CD8 T-lymphocytes where FACSDiva had significantly lower values (P < 0.05). The B-cell counts were unaffected when either of the instruments or softwares were used, while the natural killer (NK) cells (CD16 + 56 positive cells) showed similar trend like CD3 and CD4 counts with significant differences in the mean cell counts between FACSCalibur, Cell Quest Pro (240 +/- 165 cells/microl), and FACSDiva (238 +/- 163 cells/microl) versus FACSCanto with higher NK cell counts (260 +/- 176 cells/microl). CONCLUSIONS: The enumeration of lymphocyte subsets was comparable between FACSCalibur, Cell Quest Pro, and FACSDiva, based analysis and it was significantly different than FACSCanto software based analysis. Our observations suggest that FACSDiva software should be preferred over the FACSCanto software for immunophenotyping on FACSCanto flow cytometer and the laboratories should report the instrument and software used for the specimen analysis while reporting immunophenotyping results.     

Restoration of blood total glutathione status and lymphocyte function following alpha-lipoic acid supplementation in patients with HIV infection

OBJECTIVES: To determine whether supplementation with alpha-lipoic acid (ALA), a glutathione-replenishing disulfide, modulates whole blood total glutathione (GSH + GSSG) levels and improves lymphocyte function in human immunodeficiency virus (HIV)-infected subjects with history of unresponsiveness to highly active antiretroviral treatment (HAART). DESIGN AND SETTING: Randomized, double-blinded, placebo-controlled trial conducted at two study sites: an eye clinic at a county hospital in San Jose and a research clinic in San Francisco, California. SUBJECTS: A total of 33 HIV-infected men and women with viral load >10,000 copies/cm(3), despite HAART, aged 44-47 years, approximately 36% nonwhite, were enrolled. INTERVENTION: Patients were randomly assigned to receive either ALA (300 mg three times a day) or matching placebo for 6 months. MAIN OUTCOME MEASURES: The change over 6 months in blood total glutathione status, lymphocyte proliferation response to T-cell mitogens, CD4 cell count, and viral load in patients receiving ALA compared to placebo. RESULTS: The mean blood total glutathione level in ALA-supplemented subjects was significantly elevated after 6 months (1.34+/-0.79 vs. 0.81+/-0.18 mmol/L) compared to insignificant change (0.76+/-0.34 vs. 0.76+/-0.22 mmol/L) in the placebo group (ALA vs. placebo: p=0.04). The lymphocyte proliferation response was significantly enhanced or stabilized after 6 months of ALA supplementation compared to progressive decline in the placebo group (ALA vs. placebo: p<0.001 with phytohemagglutinin; p=0.02 with anti-CD3 monoclonal antibody). A positive correlation was seen between blood total glutathione level and lymphocyte response to anti-CD3 stimulation (R(2)=0.889). There was no significant change in either HIV RNA level or CD4 count over 6 months in the ALA-supplemented compared to the control group. CONCLUSION: Supplementation with alpha-lipoic acid may positively impact patients with HIV and acquired immune deficiency syndrome by restoring blood total glutathione level and improving functional reactivity of lymphocytes to T-cell mitogens.     

HIV/AIDS患者B7-H1的表达特点及与疾病进展关系研究

目的 研究HIV/AIDS患者外周血mDC及不同亚群T淋巴细胞B7-H1及PD-1的表达水平,分析其与疾病进展的相关性,探讨B7-H1及PD-1信号通路在HIV感染中的作用.方法 采集中国医科大学附属第一医院艾滋病研究所红丝带门诊36例未经抗病毒治疗的HIV/AIDS患者(无症状HIV组、AIDS组)及20名健康对照组...     

Increased leucine turnover and insulin resistance in men with advanced HIV infection.

BACKGROUND: The purpose of this study was to determine if patients with advanced HIV infection exhibit increased rates of leucine turnover and to determine dose effects of insulin on suppression of leucine turnover. We also wished to evaluate hepatic glucose production and re-examine peripheral insulin sensitivity in HIV infected adults. METHODS: Results from 9 males with advanced HIV disease (96-121% ideal body weight, NW-AIDS) and 3 males (80-88% ideal body weight, UW-AIDS) were compared to age and weight matched normal volunteers (NW-C and UW-C). Each subject underwent basal leucine turnover studies followed by insulin dose response studies using a step-up hyperinsulinemic euglycemic clamp (insulin dose: 10, 20 and 120 mU/m2/min) and the stable isotope [1-13C]leucine. Hepatic glucose production was measured using the stable isotope d-6,6(2)H2-glucose. Resting energy expenditure (REE) was measured by indirect calorimetry and a 24-hour food recall was obtained. Viral load, Karnofsky score, and CD4 counts were measured in AIDS subjects. RESULTS: All subjects with AIDS had higher rates of leucine appearance (leucine Ra) than controls. Although both AIDS and Controls demonstrated suppression of leucine Ra with insulin, suppression was less in AIDS subjects. There was a strong relationship between leucine Ra and viral load (r = 0.87, P = 0.02). The AIDS subjects exhibited peripheral insulin resistance when compared to controls. CONCLUSIONS: Our results suggest that patients with HIV have both peripheral insulin resistance and resistance to the anticatabolic effects of insulin.     

The safety profile and antiviral activity of the combination of stavudine, didanosine, and nelfinavir in patients with HIV infection

We assessed the safety profile, tolerability, and antiviral effect of 12 weeks of triple combination therapy with stavudine (d4T), didanosine (ddI), and nelfinavir in patients who had not previously received therapy with d4T, ddI, or a protease inhibitor. We also assessed the effect of the buffered tablet formulation of ddI on the pharmacokinetics of nelfinavir. The study had a single-arm, open-label design and enrolled patients aged > or =18 years who had HIV infection and > or =10,000 plasma HIV RNA copies/mL. Patients received the full recommended doses of oral d4T, ddI, and nelfinavir. Efficacy was assessed in terms of change from baseline in plasma HIV RNA and CD4+ cell counts, as well as in terms of the proportion of patients achieving HIV RNA levels <400 copies/mL. The first 10 patients enrolled in the study were included in a substudy to determine the effects of the buffered tablet formulation of ddI on the pharmacokinetic profile of nelfinavir. A dose of ddI was given 1 hour before nelfinavir, after which the maximum plasma concentration (Cmax), time to Cmax (Tmax), and area under the concentration-time curve (AUC) of nelfinavir were determined. A total of 22 patients entered the trial, of whom 1 (5%) had AIDS, 12 (55%) had symptomatic HIV infection, and 9 (41%) were asymptomatic. The median baseline CD4+ cell count was 315 cells/microL (range, 70-709 cells/microL), and the median plasma viral load was 4.8 log10 copies/mL (range, 4.0-5.6 log10 copies/mL). ddI had no clinically significant effects on the plasma pharmacokinetics of nelfinavir. At the end of 12 weeks of treatment, the mean (+/- SE) decrease in plasma viral load was 1.36+/-0.24 log10 copies/mL, and 8 of 16 patients (50%) achieved plasma HIV RNA levels <400 copies/mL; the mean (+/- SE) increase in CD4+ cell count was 111.4+/-31.7 cells/microL. Patients who were judged to be compliant with antiretroviral therapy (ie, who missed <7 days of all 3 study drugs during 12 weeks of treatment) experienced mean decreases in viral load exceeding 2.0 log10 copies/mL, and 6 of 7 patients achieved HIV RNA levels <400 copies/mL after 12 weeks of therapy. Although 95% of patients reported an adverse event of grade 1 or higher, only 1 patient experienced a grade 3 or 4 adverse event (maculopapular rash) related to nelfinavir. As reflected in the Cmax, Tmax, and AUC, administration of ddI 1 hour before nelfinavir did not influence the pharmacokinetic profile of the protease inhibitor. Triple drug therapy with d4T, ddI, and nelfinavir was well tolerated and associated with few clinically significant toxicities. This treatment resulted in substantial reductions in viral load and improvements in CD4+ cell count over 12 weeks.     

新疆100例HIV／AIDS患者机体细胞免疫与合并机会性感染关系的研究

目的探讨人类免疫缺陷病毒（HIV）感染者和艾滋病（AIDS）患者机体细胞免疫与合并机会性感染的关系。方法总结新疆100例HIV／AIDS患者临床资料,分析CD3^＋、CD4^、CD8^＋细胞水平,及CD4^＋细胞数与发生机会性感染的关系。结果HIV／AIDS患者合并机会感染CD3^＋、CD4^＋细胞数明显低于未合并机会感染组且差异均具有统计学意义（t=-2．073,t=-4．087,P〈0．05）,CD8^＋、CD4^＋／CD8^＋比值则差异无统计学意义（P〉0．05）。CD3^＋细胞数与CD4^＋细胞数的变化呈正相关（r=0．481,P〈0．05）,与CD8^＋细胞数的变化呈高度正相关（r=0．954,P〈0．05）。CD4^＋细胞含量〈200个／μl时,发生机会性感染高于CD4^＋细胞含量为200—500个／μl时,且差异有统计学意义（r=17．272,P〈0．05）。在CD4^＋细胞含量〈200个μl的HIV／AIDS患者中以PCP的合并感染为最高27．27％,其次弓形虫和结核（22．73％,13．64％）。结论HIV／AIDS患者并发机会性感染与免疫抑制程度有关,CD4^＋的水平是目前监测机会性感染的重要参考依据,不同地区机会性感染疾病谱略有不同,临床可采取相应的预防性治疗措施。     

Flying in the face of resistance: antiviral-independent benefit of HIV protease inhibitors on T-cell survival

Human immunodeficiency virus (HIV) infection results in excessive apoptosis of infected and uninfected cells, mediated by host and viral factors present in plasma. As HIV protease inhibitors (PIs) have intrinsic antiapoptotic properties, we questioned whether HIV PIs could block HIV-induced CD4+ T-cell death independent of their effects on HIV replication. We demonstrate that HIV PIs block the death of CD4+ T cells induced by HIV glycoprotein 120 (gp120), Vpr, and Tat, as well as host signals Fas ligand, tumor necrosis factor, and tumor necrosis factor-related apoptosis-inducing ligand. Using gp120/CXCR4 as a model, we show that the HIV PIs specifically block mitochondrial apoptosis signaling. Furthermore, HIV PIs inhibit CD4+ T-cell death induced by viruses with high-level resistance to PIs (P<0.01) and apoptosis induced by serum of HIV patients with known resistance to HIV PIs (P=0.01). Together, these results show that HIV PIs block CD4+ T-cell death and have a beneficial effect on CD4+ T-cell survival despite PI resistance.     

Naive HIV/HCV-coinfected patients have higher intrahepatic pro-inflammatory cytokines than coinfected patients treated with antiretroviral therapy

In the era of antiretroviral therapy, liver disease has emerged as an important cause of morbidity and mortality in HIV/hepatitis C virus (HCV) coinfected patients. It is believed that HCV is a non-cytopathic virus and that T-cell-mediated events (including the production of pro-inflammatory cytokines) have an important role in promoting both liver damage and viral clearance. Whether HIV coinfection or antiretroviral therapies influence such events is still unclear. In the current study, we compared the expression of NKp46 (a natural killer cell marker), CD3 (a T-cell marker), interferon-gamma (IFN-gamma), tumour-necrosis factor-alpha (TNF-alpha; pro-inflammatory cytokines) and interleukin-10 (IL-10; an anti-inflammatory cytokine) mRNA in the liver of naive HIV/HCV-coinfected patients (group one, n=14), coinfected patients treated with antiretroviral therapy (group two, n=23) and naive HCV mono-infected patients (group three, n=24). All three groups had comparable HCV viremia, with coinfected patients showing similar and relatively high CD4+ T-cell counts and significantly different HIV vireamia. Interestingly, when compared to groups two and three, group one showed significantly higher intrahepatic mRNA levels for CD3, IFN-gamma and TNF-alpha, whereas the expression of NKp46 and IL-10 were comparable in all three groups. Further, higher histopathological grading scores within each group were independently associated with higher mRNA contents for CD3 and IFN-gamma and higher serum alanine aminotransferase levels at the time of liver biopsy. Together, these results suggest that HIV infection may exacerbate the immune-mediated inflammatory response in the liver of patients chronically infected with HCV and antiretroviral therapy may prevent this effect.     

Independent epidemics of heterosexual and homosexual HIV infection in South Africa--survival differences

Survival with HIV infection is shorter in sub-Saharan Africa than in developed countries. The pattern of HIV transmission in our region has changed from homosexual to heterosexual, with viral subtypes similar to those in North America/Europe and Central Africa, respectively. We compared survival for the two transmission patterns after AIDS, and after the first CD4+ lymphocyte counts < 200/microliter and < 50/microliter, for adults presenting 1988-1993. Antiretroviral therapy was excluded. There were 180 homosexuals (63% White, 56% employed) and 314 heterosexuals (67% Black, 34% employed). Extrapulmonary tuberculosis was the AIDS-defining diagnosis in 36/90 heterosexuals and 5/58 homosexuals (p < 0.0001). Survival after AIDS was longer in heterosexuals (p = 0.0015), but AIDS occurred earlier as shown by their higher CD4+ count at AIDS onset (median 98/microliter vs. 40/microliter; p = 0.036). Survival was similar in the two groups after first CD4+ count < 200/microliter and < 50/microliter. Race, socioeconomic status and morbidity are markedly different in the two transmission groups. AIDS occurs with less severe immune suppression in heterosexuals, with correspondingly longer survival. Survival after defined CD4+ counts, however, is remarkably similar.      

中国HIV早期感染者CD+4CD+25Foxp3+调节性T淋巴细胞变化研究

目的 研究1年以内感染HIV的感染者(早期感染者,EHI)体内CD+4 CD+25 Foxp3+调节性T淋巴细胞水平及其与疾病进展相关性.方法 随机选取51例HIV感染者,依据感染时间及CD+4 T淋巴细胞水平分为3组:EHI组30例、HIV组15例、AIDS组6例,20名健康人作为对照组,各组对象的年龄、性别具有可比性.用EDTA抗凝管采集全血,应用FACSAria流式细胞仪及Foxp3染色试剂盒,检测外周血单个核细胞CD+4CD+25Foxp3+调节性T淋巴细胞表达水平,分析EHI者及全部HIV感染者CD+4 CD+25Foxp3+调节性T淋巴细胞表达水平与CD+4T淋巴细胞数量、病毒调定点、病毒载量及淋巴细胞活化水平间的相关性.结果 健康对照组、EHI组、HIV组及AIDS组CD+4C+25Foxp3+T淋巴细胞百分率逐级上升,其中EHI组CD+4CD+25Foxp3+T淋巴细胞百分率[3.79(2.11～5.43)%]低于AIDS组[8.09(4.90～8.90)%],差异有统计学意义(Z=-2.29,P=0.022);EHI组CD+4 CD+25Foxp3+T淋巴细胞百分率与病毒调定点正相关(r=0.479,P=0.038),与CD4T淋巴细胞计数呈负相关(r=-0.455,P=0.011),与CD+3 HLA+T淋巴细胞呈正相关(r=0.533,P=0.002).结论 中国EHI者CD+4 CD+25Foxp3+调节性T淋巴细胞百分率高与高病毒调定点及低CD+4 T淋巴细胞数量相关,提示CD+4 CD+25Fox3+调节性T淋巴细胞是加速HIV感染早期疾病进展的因素之一.     

Change in T-lymphocyte count after initiation of highly active antiretroviral therapy in HIV-infected patients with history of Mycobacterium avium complex infection

OBJECTIVE: To compare changes in CD4+, CD8+ and total lymphocyte counts after initiation of highly active antiretroviral therapy (HAART) between HIV-infected patients with and without a recent history of Mycobacterium avium complex (MAC) infection. METHOD: Matched exposed-non-exposed retrospective cohort study. RESULTS: Fifty-one patients with a recent history of MAC infection (MAC+) started a combination of at least three antiretroviral drugs. They were individually matched to 145 patients without any history of MAC infection (MAC-) according to CD4+ T-cell count (+/- 30 cells/mm3), previous experience of antiretroviral treatment, AIDS clinical stage at the time of HAART initiation (baseline), age (+/- 10 years) and gender. MAC+ and MAC- patients presented comparable median levels of total lymphocytes (488 vs 688/mm3, P=0.09), CD4+ (11 vs 16/mm3, P=0.15), CD8+ count (359 vs 386/mm3, P=0.39) and plasma HIV RNA (5.3 vs 5.1 log10 copies/ml, P=0.22) at baseline. After 6 months on HAART, the median increase of CD4+ T-cell count was 28 cells/mm3 (interquartile range [IQR]: 1-63) in MAC+ and 72 cells/mm3 (IQR: 34-120) in MAC- patients (P<0.0001), whereas the percentage of CD4+ T cells was not significantly different between the two groups (P=0.13). Comparable differences were observed for total lymphocytes and CD8+ T cells (P<0.001). The 6 months decline of plasma HIV RNA was not significantly different according to MAC exposure (-1.6 in MAC+ vs -1.8 log10 copies/ml in MAC- patients, P=0.65). Results were confirmed after adjustment for other characteristics than the matching variables and after taking into account potential informative bias due to unbalanced number of deaths between the two groups. CONCLUSION: MAC infection at the time of HAART initiation is an important deleterious factor for immune reconstitution. A better understanding of the underlying mechanism and an evaluation of additional treatment strategies are necessary to help immune restoration in such circumstances.     

中国HCV/HIV合并感染者T淋巴细胞表面CD81、CXCR3表达的研究

目的探讨T淋巴细胞表面受体CD81、CXCR3，在丙肝病毒（HCV）单纯感染，艾滋病病毒（HIV）单纯感染和HCV／HIV合并感染过程中的表达及意义。方法采用流式细胞术，检测HCV感染组（n=21），HIV感染组（n=14），HCV／HIV感染组（n=28）及正常对照组（n=30）人外周血CD4^＋T淋巴细胞和CD8^＋T淋巴细胞表面CD81、CXCR3的表达。结果HIV感染组及HCV／HIV合并感染组CD4^＋T细胞表面CD81、CXCR3表达显著降低（P〈0．001），CD8^＋T细胞表面CD81、CXCR3表达显著升高（P〈0．001）；HCV感染组CD4^＋及CD8^＋T细胞表面CXCR3表达轻度升高但差异不显著，CD81在CD4^＋T细胞表面轻度升高而在CD8^＋T细胞表面明显升高（P〈0．01）。结论中国HCV／HIV合并感染患者外周血T淋巴细胞表面受体CD81、CXCR3，在CD4^＋T细胞表面表达降低，而在CD8^＋T细胞表面表达升高。     

2010-2014年广东省中山市吸毒人群HIV感染率及新发感染率分析

目的 获得广东省中山市吸毒人群2010-2014年人类免疫缺陷病毒(human immunodeficiency virus, HIV)感染率变化趋势和新发感染率,评估吸毒人群HIV流行形势。方法 利用2010-2014年中山市强制戒毒所(戒毒所)全员HIV监测和哨点监测数据分析吸毒人群HIV感染率。采用Spectrum/EPP 模型、首次检测CD4+ T淋巴细胞计数及开放性队列,三种方法估计2010-2014年吸毒人群新发感染率。结果 2010-2014年,戒毒所全员监测HIV感染率分别为2.88%(52/1804)、3.33%(64/1920)、3.51%(62/1764)、3.40%(94/2765)和3.94%(86/2183),不同年份间HIV感染率差异无统计学意义(2=3.44,P=0.49)。2010-2014年哨点监测,注射吸毒人群HIV感染率分别为5.13%(12/234)、6.36%(18/283)、4.26%(12/282)、4.94%(12/243)和4.93%(10/203), 差异无统计学意义(2=1.36,P=0.85);非注射吸毒人群HIV感染率分别为1.81%(3/166)、1.13%(2/177)、 0.78%(1/129)、0.60%(1/166)和0.00%(0/197),差异无统计学意义(2=4.35,P=0.36)。2010-2014年新发感染率Spectrum/EPP 模型估计结果维持在0.23%左右;首次检测CD4+ T淋巴细胞计数估计最近一年新发感染率分别为0.28%、0.16%、0.29%、0.11%和0.10%,差异无统计学意义(2=3.83,P=0.43);1971例重复检测者组成的开发性队列,合计随访4473人年,4例出现HIV抗体阳转,HIV阳转率为0.09/100人年(95%CI:0.01~0.18/100人年)。结论 2010-2014年,中山市吸毒人群HIV感染率维持在5%以下,新发感染率维持在0.3%以下,处于低水平。     

HIV及HBV重叠感染患者生化免疫指标的检测价值

[目的] 探讨人类免疫缺陷病毒(HIV)与乙型肝炎病毒(HBV)重叠感染患者生化免疫指标的变化特点.[方法] 比较30例HIV感染、32例HBV感染及20例HIV、HBV重叠感染患者(HIV/HBV组)肝功能、免疫功能、血生化常规指标的差异.[结果] ①HBV组CD3+、CD4+、CD4+/CD8+高于HIV组、HIV/HBV组(P<0.05),HIV、HIV/HBV组组间比较差异无显著性(P>0.05);②HBV组谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆红素(TBil)均高于其他两组(P<0.05),HIV组与HIV/HBV组组间比较差异无显著性(P>0.05);③HIV/HBV组HIV RNA、HBV DNA病毒载量均高于HIV组(P<0.05);④HBV组血红蛋白(Hb)水平高于(P<0.05),其血小板计数(PLT)、红细胞(RBC)水平均低于HIV组与HIV/HBV组(P<0.05),而HIV组、HIV/HBV组Hb、PLT、RBC组间比较差异无显著性(P>0.05).[结论] HIV/HBV重叠感染后,机体免疫功能进一步降低,可促进两者病情的进展,但其可能减轻HBV感染患者肝脏炎性损伤,但对HIV所引起贫血无明显影响.