2',5'-oligoadenylate synthetase, neopterin and beta 2-microglobulin in asymptomatic HIV-infected individuals

This study examined 2',5'-oligoadenylate (2,5A) synthetase activity in 26 individuals during the asymptomatic phase of HIV infection and its correlation with neopterin or beta 2-microglobulin. In HIV-antibody-positive (HIV-Ab+) asymptomatic people, both neopterin and beta 2-microglobulin levels in sera were significantly elevated; in contrast, 2,5A-synthetase activity in peripheral blood mononuclear cells was not significantly higher than in HIV-antibody-negative controls. The 2,5A-synthetase levels in symptomatic people (AIDS-related complex and AIDS) were significantly higher than in either asymptomatic or control individuals. However, within the group of HIV-infected asymptomatic individuals, all three markers were positively correlated. In this group, neopterin values were negatively correlated with the number of CD4+ lymphocytes while a positive correlation was found between 2,5A-synthetase and the number of CD8+ lymphocytes. Asymptomatic people with detectable serum HIV p24 antigen had significantly higher 2,5A-synthetase, neopterin, beta 2-microglobulin and number of CD8+ lymphocytes. This study suggests that elevated 2,5A-synthetase activity may reflect a different aspect of host response to HIV infection than do elevated neopterin or beta 2-microglobulin.     

Prognostic value of an elevated CD8 lymphocyte count in HIV infection. Results of a prospective study of 152 asymptomatic HIV-positive individuals.

OBJECTIVE: To evaluate the prognostic value of an elevated CD8 lymphocyte count in the early stages of HIV infection. DESIGN: A prospective study ongoing since January 1986. METHODS: One hundred and fifty-two asymptomatic HIV-positive individuals with a CD4 lymphocyte count > 400 x 10(6)/l at enrollment were included. Disease progression was defined as a CD4 count < 200 x 10(6)/l. RESULTS: During the follow-up period, CD4 count decreased in 33 individuals; CD8 count increased to > 1500 x 10(6)/l in 38 individuals and doubled in 35. The risk of a decreasing CD4 count was estimated to be 1.7-fold higher, although not significantly so, after the elevation of the CD8 count to > 1500 x 10(6)/l than before or in the absence of such an increase. However, this predictive value disappeared when five baseline parameters found to predict the outcome (neopterin, beta 2-microglobulin, p24 antigen, anti-p18 antibody and immunoglobulin A) were adjusted. CONCLUSION: Elevated CD8 count appears to be a weak marker for disease progression.     

Serum soluble CD8 molecule is a marker of CD8 T-cell activation in HIV-1 disease

To characterize CD8 T-cell activation during HIV-1 infection we measured serum soluble CD8 (sCD8) levels longitudinally in seroconverters and in individuals with established HIV infection who were in different stages of illness. CD8 T-cell activation occurs very early in HIV infection. Serum sCD8 levels were elevated in 91.5% of the first seropositive samples in seroconverters. Furthermore, CD8 T-cell activation persists throughout HIV infection. sCD8 predicted the occurrence of AIDS in HIV-seropositive individuals and so the addition of serum sCD8 levels to CD4 T-cell measurements increased the power in predicting the onset of AIDS. The serum level of sCD8 was particularly relevant to the prediction of subsequent CD4 T-cell fall relatively early in infection, for example, in the 3 years after seroconversion. However, later in HIV infection, for example within 2 years prior to development of AIDS, sCD8 levels were less predictive. sCD8 correlated with levels of beta 2-microglobulin and neopterin, which reflect activation of cell types other than CD8. Thus, serum sCD8 level can be a useful marker of specific CD8 T-cell activation, and is an independent predictor of prognosis in HIV infection.     

Progression to AIDS in the majority of asymptomatic HIV-infected people

Sixty-eight asymptomatic HIV-seropositive people with a CD4 lymphocyte count above 400/mm3 at the first examination were followed up every year over a 3-year period, by monitoring the biological markers of AIDS (CD4 lymphocyte decrease, loss of anti-p24 or anti-p17 antibodies, positive p24 antigenemia, increase of erythrocyte sedimentation rate, and of serum levels of immunoglobulin G. immunoglobulin A, neopterin and beta 2-microglobulin). The percentages of subjects positive for at least one marker at the first, second, third and fourth examinations were 66, 88, 94 and 97%, respectively. The increase in the number of markers with time was significant (chi-square test; P less than 0.001). This increase suggests a progression to AIDS in the majority of asymptomatic seropositive subjects, even those without a decreased CD4 lymphocyte count.     

HIV／AIDS患者血浆病毒载量及外周血T淋巴细胞亚群的变化

目的：观察国内HIV／AIDS患者血浆病毒载量和外周血CD4^ 、CD8^ T淋巴细胞的变化，探讨这些变化的临床意义。方法：选择未经抗病毒治疗的HIV／AIDS患者124例，用bDNA法检测血浆病毒载量，并用流式细胞仪检测外周血CD4^ 、CD8^ T淋巴细胞。结果：AIDS患者的血浆病毒载量明显高于HIV感染者，血浆病毒载量与CD4^ 细胞计数呈显著负相关，但其最高峰位于CD4^ 细胞计数100／μl处，然后随着CD4^ 细胞计数的下降而减少。CD4^ T细胞计数为AIDS组＜HIV组＜正常对照组：HIV感染者的CD8^ T细胞计数显著高于正常组和AIDS组，而AIDS患者CD8^ T细胞数则随着CD4^ T细胞减少而下降。结论：血浆病毒载量随着疾病进展而显著升高，但在疾病晚期则有所降低。外周血CD4^ T细胞计数随着疾病的进展而进行性减少；CD8^ T细胞计数在感染早期显著升高，进入晚期则减少。在评价HIV感染者和AIDS患者病情时，应结合病毒载量、CD4^ 、CD8^ T细胞计数综合分析。     

Levels of soluble CD8 antigen and circulating immune complexes in intravenous drug abusers: relationships to HIV antibody serology

A total of 36 intravenous drug abusers (IVDA) were studied for circulating immune complexes (CIC) and serum soluble CD8 antigen (sCD8). None had symptoms or signs of AIDS-related complex or AIDS. sCD8 levels were significantly higher in 18 patients who had HIV antibody (Ab) compared with 18 patients who were HIV Ab negative (1640 +/- 578 virus 804 +/- 264 U/ml, p less than 0.0001). In HIV Ab+ patients but not in HIV Ab- patients, sCD8 levels significantly correlated with percentages and absolute numbers of activated CD3+DR+ peripheral blood mononuclear cells (p = 0.0024 and 0.0183, respectively). Also in HIV Ab+ patients, CIC levels were significantly greater for both anti-C3 binding (13.1 +/- 11.1 versus 2.9 +/- 3.4 micrograms/ml, p = 0.002) and C1q binding (23.5 +/- 20.2 versus 6.3 +/- 4.3 micrograms/ml, p = 0.001) CIC. Serum C4 concentrations were lower in the HIV Ab+ patient group (33.9 +/- 10.1 versus 41.6 +/- 12.4 mg/dL, p = 0.043). In the seropositive group, IgG levels were higher (2206 +/- 859 versus 1615 +/- 645 mg/dl) and total CD4 cell counts were lower (757 +/- 344 versus 1172 +/- 402 cells per mm3), but at a less significant level (p = 0.024 and 0.005, respectively), than that seen for sCD8 and C1q CIC differences. These results suggest that elevations of both the lymphocyte activation marker sCD8 and antigen nonspecific CIC characterize earlier stages of HIV infection in IVDA.     

Prognostic value of single measurements of beta-2-microglobulin, immunoglobulin A in HIV disease after controlling for CD4 lymphocyte counts and plasma HIV RNA levels

The interrelationships between the CD4 lymphocyte count, plasma viral load [human immunodeficiency virus (HIV) RNA], beta-2-microglobulin (beta2-M) and immunoglobulin A (IgA) and the mortality risk was explored in 234 HIV-infected individuals (median CD4 count 230 cells/mm3, range 1-1,247). Product-moment correlation analysis was used to study the association between beta2-M, IgA and HIV RNA. A proportional hazards Cox model was used to estimate the relative hazard (RH) of death. Both beta2-M (r = 0.49, p < 0.0001) and IgA (r = 0.42, p < 0.0001) were positively correlated with HIV RNA. High beta2-M levels were associated with an increased risk of death in both univariate Cox analysis and after adjustment for HIV RNA, CD4 lymphocyte count and age [RH = 1.16 per 100 nmol/l higher beta2-M, 95% confidence interval (CI) 1.05-1.27]. Raised IgA levels were associated with shorter survival in individuals with a CD4 count above 50 cells/mm3 in univariate analysis as well as after adjusting for age and CD4 lymphocyte count (RH = 1.19 per 10 micromol/l higher IgA, 95% CI 1.01-1.39). However, this association was no longer significant after further adjusting for HIV RNA. In conclusion, beta2-M levels provided additional prognostic information for survival to the information obtained by CD4 count and HIV RNA levels, whereas serum IgA only was a weak prognostic marker in this fairly progressed cohort.     

Clinical and laboratory predictors of survival in Gambian patients with symptomatic HIV-1 or HIV-2 infection.

OBJECTIVES: To determine which clinical and immunological features of patients with symptomatic HIV-1 and HIV-2 infection best predict survival in The Gambia. METHODS: All patients presenting to two hospitals in The Gambia between January 1987 and June 1990 with symptoms or signs suggesting chronic HIV infection were tested for HIV-1 and HIV-2 antibodies. Eighteen HIV-1 and 31 HIV-2-infected patients were recruited to the study, investigated intensively on admission and followed up until the end of 1990. Presenting clinical features, such as Karnofsky score, diagnosis of AIDS according to World Health Organization Bangui or Centers for Disease Control criteria and number of associated infections, together with five immunological measurements, as well as type of HIV infection, were related to length of survival using proportional hazard models fitted to Kaplan-Meier plots of survival times. RESULTS: Karnofsky score and diagnosis of AIDS were the best clinical predictors of survival. Type of HIV infection or number of associated infections did not predict outcome. The most powerful laboratory predictors were log(e) serum neopterin level, CD4 cell count and log(e) serum beta 2-microglobulin (beta 2M) level. The estimated median survival times (90% confidence interval) of the HIV-1 and HIV-2-infected were six (4-11) and 13 (9-20) months, respectively. These survival times do not differ significantly. CONCLUSIONS: The Karnofsky score and measurements of serum neopterin or beta 2M, which are easier and cheaper to perform than CD4 counts, may prove to be useful guides to prognosis for HIV infection in Africa.     

Cross-sectional study of immunologic abnormalities in intravenous drug abusers on methadone maintenance in New York City

One hundred and ninety-nine patients with a history of intravenous drug abuse, and enrolled on the St Luke's-Roosevelt Hospital Center Methadone Program, had baseline evaluations performed from September 1984 to April 1987. The study was designed to examine immunologic parameters associated with HIV seropositivity and those predictive of progression to AIDS-related complex (ARC) and AIDS. Sixty-four patients (32%) had antibodies to HIV by enzyme-linked immunosorbent assay (ELISA), with confirmation by Western blot and none of these patients had ARC or AIDS at the time of initial evaluation. The mean values for white blood-cell count, absolute lymphocyte count, proportion and absolute CD4, and CD4/CD8 ratio were decreased significantly in the HIV-seropositive group compared with the HIV-seronegative group. On the other hand, levels of circulating beta 2-microglobulin, SCD8, SIL-2R, and HIV p24 antigen were significantly elevated in the HIV-seropositive group compared with the HIV-seronegative group.     

Markers for disease progression in intravenous drug users infected with HIV-1.

We evaluated the number and percentage of CD4+ T cells, the ratio of CD4+ T cells to CD8+ T cells, the serum levels of beta 2- microglobulin and urinary levels of neopterin for their ability to predict disease progression (defined as clinical AIDS and/or oral candidiasis in combination with a CD4+ T cell count less than 400 x 10(6)/l). Thirty-eight intravenous drug users (IVDU) infected with HIV-1 without HIV-1-related symptoms were followed for a median observation period of 45 months. Cumulative incidence of disease progression was computed by the product-limit approach. The CD4+: CD8+ T-cell ratio (P = 0.001), the number (P = 0.002) and percentage (P = 0.05) of CD4+ T cells, and urinary neopterin (P = 0.007) were significant predictors for disease progression. Serum beta 2-microglobulin, which has been found to be of similar prognostic value as neopterin in homosexual men, did not show predictive power in this study of IVDU. The urinary neopterin concentrations obtained at entry of the study correlated with the values of the CD4+:CD8+ T-cell ratio and number and percentage of CD4+ T cells which were obtained at the end of the follow-up. These findings should help to identify, among HIV-1-infected IVDU, those at high risk of disease progression.     

艾滋病的高效抗逆转录病毒治疗、疗效观察及其对免疫功能的影响

目的 为探讨艾滋病高效抗逆转录病毒治疗、疗效观察及其对免疫功能的影响.方法 应用HAART疗法对4例有严重免疫功能低下的HIV/AIDS病人进行治疗.结果 所有病人在治疗4周HIV复制被明显抑制,血浆病毒载量平均下降1.99log/ml(0.73～2.46log/ml),CD_8~ 、CD_4~ 细胞和血浆IL-2浓度在4～12周后持续性显著增高,上升幅度分别为67.2%,103.0%,255.1%,而血浆sIL-2R、IL-6、TNF-α、sTNFR-I、Neopterin浓度在治疗4～12周后持续下降至正常水平或以下.HAART治疗后各因素变化间的相关性分析显示,CD_4~ 细胞数与CD_8~ 、CD_3~ 细胞和血浆IL-2浓度之间,血浆病毒载量与sIL-2R、IL-6、TNF-α、sTNFR-I、Neopterin之间,sTNFR-I和Neopterin与sIL-2R、IL-6、TNF-α之间均存在明显正直线相关性;而CD_4~ 细胞数与血浆病毒载量、sIL-2R、sTNFR-I、Neopterin之间.以及IL-2和sIL-2R之间则有明显负直线相关性.结论 抗病毒治疗效果、病毒复制和免疫活化间具有密切关系,HAART治疗能快速有效地抑制HIV-1的复制,纠正机体免疫功能紊乱和重建免疫功能;外周血CD_4~ 细胞数、血浆病毒载量、IL-2、sIL-2R、TNF-α、sTNFR-I、Neopterin的浓度变化可以作为HAART治疗效果评价的重要指标.     

Loss of CD4 T lymphocytes in patients infected with human immunodeficiency virus type 1 is more pronounced in the duodenal mucosa than in the peripheral blood. Berlin Diarrhea/Wasting Syndrome Study Group.

Although changes in T lymphocyte subset distribution in the peripheral blood of patients infected with human immunodeficiency virus (HIV) are well defined it is not known whether these changes reflect changes in lymphoid compartments clearly involved in HIV related disease like the intestinal mucosa. This study analysed lymphocytes isolated simultaneously from the peripheral blood and duodenal biopsy specimens by three colour flow cytometry in eight asymptomatic HIV infected patients, 26 AIDS patients, and 23 controls. The proportion of CD4, CD8, CD4-CD8-, or gamma delta T cells did not correlate between circulating and duodenal T cells. CD4 T cells were reduced in the peripheral blood (7.5% (25th-75th percentile, 2-16%) v 52% (41-63%), p < 0.0005) and even more reduced in the duodenum (1% (1-2%) v 36% (23-57%), p < 0.0005) of AIDS patients compared with controls. Patients with asymptomatic HIV infection had intermediate CD4 T cells in the peripheral blood (24% (22-35%); p < 0.002 v controls; p < 0.01 v AIDS) but like AIDS patients very low CD4 T cells in the duodenum (3% (1-6%); p < 0.002 v controls). The ratio of duodenal to circulating CD4+ T cells was significantly reduced to 0.2 (0-1) in AIDS patients (p < 0.001) and even to 0.1 (0.04-0.5) in asymptomatic HIV infected patients (p < 0.002) compared with 0.72 (0.44-0.95) in controls. These findings show an early and preferential loss of duodenal CD4 T cells in HIV infection. Immunological abnormalities in HIV infection are distinct between lymphoid compartments, and profound immunodeficiency may occur in the intestinal immune system although circulating T cells are largely preserved.     

Naturally occurring soluble CD4 in patients with human immunodeficiency virus infection.

To investigate its use as a marker of disease severity, serum soluble CD4 (sCD4) was measured by ELISA in patients with human immunodeficiency virus (HIV) infection. Levels of sCD4 were higher in patients than in controls (P less than .001) but did not increase with disease severity. sCD4 release per CD4 lymphocyte showed a linear increase with disease severity and performed as well as beta 2-microglobulin, a widely used marker. To study the role of sCD4 in the pathogenesis of HIV infection, an ELISA to detect sCD4 complexed with glycoprotein 120 (gp120) HIV envelope protein was developed. Preformed sCD4-gp120 complexes were not detectable in patient serum, but addition of recombinant gp120 showed that circulating sCD4 is capable of binding HIV envelope proteins. This study indicates that the sCD4-to-CD4 lymphocyte ratio increases linearly with disease severity and may be a useful marker of CD4 lymphocyte damage. In addition, serum sCD4 can bind viral particles, which may have implications for the use of recombinant sCD4 as a therapy in HIV infection.     

Association of antibody to human immunodeficiency virus type 1 core protein (p24), CD4+ lymphocyte number, and AIDS-free time.

Serum antibody to p24 (anti-p24) and p24 antigen, alone and in combination with CD4+ lymphocyte number, were evaluated as predictors of progression of human immunodeficiency virus type 1 (HIV-1) infection. Two hundred six HIV-1-prevalent seropositive men in the Multi-center AIDS Cohort Study since 1984-1985 were studied cross-sectionally and 84 seroconverters were evaluated longitudinally. Cross-sectional analyses revealed significant associations among titer of anti-p24, CD4+ cell count, disease status (Centers for Disease Control class), and progression to AIDS. A high titer of anti-p24 was associated with lack of p24 antigenemia. Longitudinal studies of seroconverters demonstrated that a low titer of anti-p24, low CD4+ cell count, and detection of HIV-1 p24 antigen are individually strong predictors of AIDS, but only low CD4+ cell count retains its independent predictive value in multivariate analysis of the three markers during the period immediately after infection with HIV-1.     

Predictive markers for the acquired immunodeficiency syndrome (AIDS) in hemophiliacs: persistence of p24 antigen and low T4 cell count

STUDY OBJECTIVE: To investigate the predictive value of assays for human immunodeficiency virus (HIV) p24 antigen, p24 antibody, and gp120 antibody compared with T4 cell counts. DESIGN: Prospective cohort selected from persons who had HIV-antibody seroconversion. PATIENTS: Eighty-seven persons with hemophilia with an actuarial cumulative acquired immunodeficiency syndrome (AIDS) incidence of 26% (CI, 12% to 40%), 8 years after HIV-antibody seroconversion. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Human immunodeficiency virus p24 antigen was detected in 8 of 74 (11%) of the patients without AIDS and 7 of 13 (54%) of the patients with AIDS. The 2-year actuarial incidence of AIDS was 24% (CI, 0% to 48%) after detection of p24 antigen, 16% (CI, 0% to 34%) after loss of p24 antibody, 20% (CI, 0% to 45%) after loss of gp120 antibody, 31% (CI, 15% to 47%) after a T4 count of less than 200 cells/microL, and 67% (CI, 31% to 100%) after a T4 count of less than 200 cells/microL among those patients positive for p24 antigen. Very low numbers of T4 and T8 lymphocytes, presence of p24 antigen in serum, and absence of p24 antibody all had some predictive value. However, only p24 antigen (relative hazard 6.0, P = 0.008) and T4 counts (relative hazard 5.3, P = 0.002 with T4 count less than 200 cells/microL) independently predicted AIDS up to 12 months before diagnosis. CONCLUSIONS: Strong predictors of AIDS are p24 antigenemia or low T4 counts. Detection of p24 antigen is highly specific and complementary to the greater sensitivity of low T4 counts. These findings have important implications regarding prognosis, counseling, and the planning of clinical trials.     

Long-term human immunodeficiency virus infection in asymptomatic homosexual and bisexual men with normal CD4+ lymphocyte counts: immunologic and virologic characteristics.

From a prospective cohort study, 24 asymptomatic men were identified who had been antibody positive for human immunodeficiency virus (HIV) for at least 5 years (median = 9.1) with CD4+ lymphocyte counts greater than or equal to 400 cells/mm3. Of these "nonprogressors", 23 (96%) had evidence of HIV infection by either HIV culture or the polymerase chain reaction (PCR) for HIV DNA, although only 1 (4%) had a positive assay for HIV RNA (by PCR) and no one was positive for p24 antigen. Compared with 24 antibody-negative men and 14 men with AIDS, nonprogressors had higher CD8+ counts and lower natural killer cell activity. Nonprogressors had higher beta 2-microglobulin levels than did seronegative controls, suggesting some degree of immune system activation. Compared with men with AIDS, nonprogressors seemed to have a stronger antibody response to six different HIV-related proteins but did not differ significantly in neutralizing antibody or antibody-dependent cellular cytotoxic activity.     

Heat-denatured human immunodeficiency virus type 1 protein 24 antigen: prognostic value in adults with early-stage disease

CD4(+) lymphocyte count and human immunodeficiency virus (HIV) type 1 RNA level are useful for determining when to initiate antiretroviral therapy but are not used widely in developing countries due to the high cost. Heat-denatured protein 24 (p24) antigen is an inexpensive assay that predicts disease progression among persons with advanced disease but has not been assessed among persons with early-stage disease. Plasma levels of heat-denatured p24 antigen were quantified in baseline study-visit specimens obtained from injection drug users enrolled in a longitudinal cohort study of HIV-1 infection. Of the 494 study participants (median initial CD4(+) lymphocyte count, 518 lymphocytes/mm(3)), 90 (18%) progressed to acquired immunodeficiency syndrome within 5 years. p24 antigen level correlated with both CD4(+) lymphocyte count (r=-0.34; P<.0001) and HIV-1 RNA level (r=0.55; P<.0001). p24 antigen level >5 pg/mL predicted disease progression, comparable with that of cutoff CD4(+) lymphocyte count <350 lymphocytes/mm(3) and HIV-1 RNA level >30,000 copies/mL. Heat-denatured p24 antigen level predicted subsequent clinical disease progression in early-stage HIV-1 infection and correlated with both CD4(+) lymphocyte count and HIV-1 RNA level.     

Clinical correlation of the immunological markers of HIV infection in individuals from Thailand.

OBJECTIVE: To evaluate the usefulness of T-cell subsets, beta-microglobulin (B2M), p24 antigen and anti-p24 antibodies as differentiating and prognostic markers in HIV-infected Thai patients. DESIGN: Sixty-one HIV-infected patients in various stages of disease (six AIDS, three AIDS-related complex, 34 persistent generalized lymphadenopathy and 18 HIV-asymptomatic) were followed prospectively for 2 years. Patients were examined and immunological markers assessed every 6 months at least. Any HIV-related complications were treated symptomatically and clinical staging was re-evaluated at each visit. Due to financial constraints, none of the patients were given antiretroviral drugs. METHODS: T-cell subsets were enumerated by indirect immunofluorescence using OKT4 or OKT8 for T-helper and T-suppressor cells, respectively. beta 2M and p24 antigen were quantified by enzyme-linked immunosorbent assay and anti-p24 antibodies were by immunoblot assay. RESULTS: Our preliminary study revealed that the decrease in CD4+ T-cells or anti-p24 titre and the increase in p24 antigen or beta 2M correlated well with disease staging, as defined by the Centers for Disease Control. Absolute number and percentage of CD4+ T-cells, absolute number of CD8+ T-cells, beta 2M level and p24 antigen and anti-p24 antibody levels at entry could be used as reliable prognostic markers for HIV progression. The combination of p24 antigen with the number of CD4+ T-cells substantially increased the prognostic value, compared with either used alone. CONCLUSIONS: The annual rate of clinical progression from asymptomatic to symptomatic HIV infection in our study was 6.8%. The results we obtained in this preliminary study may be used as baseline data for planning future therapeutic interventions in Asian patients.     

HIV感染者外周浅表淋巴结中CD4~+T淋巴细胞计数与胶原沉积的关系研究

目的通过对不同感染阶段HIV感染者外周浅表淋巴结中CD4+T淋巴细胞、胶原蛋白、白细胞介素(interleukin,IL)-7的检测,以及CD4+T淋巴细胞计数与胶原沉积的相关性分析,探讨HIV感染后胶原沉积对CD4+T淋巴细胞的影响。方法选择HIV感染者43例,分为HIV感染无症状组和AIDS组,留取外周浅表淋巴结活体组织检查(活检)组织;另外选择非HIV感染者12名为健康对照组,同样留取其外周浅表淋巴结活检组织。利用免疫组织化学方法检测研究对象淋巴结中CD4+T淋巴细胞、Ⅰ型胶原蛋白和IL-7定量及分布情况。结果 1随着病程进展,HIV感染者外周浅表淋巴结中胶原沉积逐渐增加,AIDS组高于无症状组,无症状组高于健康对照组,差异均有统计学意义(P均0.05);2HIV感染无症状组外周浅表淋巴结中CD4+T淋巴细胞计数与健康对照组相比差异无统计学意义(P0.05),而AIDS组则显著减少(P0.01);3HIV感染者外周浅表淋巴结中CD4+T淋巴细胞计数与胶原沉积量呈负相关(R2=0.724,P=0.000),与外周血中CD4+T淋巴细胞计数呈正相关(R2=0.702,P=0.000);43组IL-7的表达水平差异无统计学意义(P0.05),而AIDS组部分患者淋巴结中IL-7呈局部聚集性分泌。结论 HIV感染后外周浅表淋巴结中胶原沉积逐渐增加导致结构破坏,可能是CD4+T淋巴细胞进行性减少的一个重要原因,虽然IL-7有随病程进展而分泌增加的趋势,但仍不足以弥补淋巴结结构破坏对CD4+T淋巴细胞的影响。     

p24 antigenaemia, CD4 lymphocyte counts and the development of AIDS.

A cohort of 111 HIV-infected haemophiliacs has been followed for up to 11 years, during which time 33 patients have been diagnosed with AIDS. Twenty-seven of the cohort developed detectable p24 antigenaemia while remaining free of AIDS. These patients experienced an increased risk of progression to AIDS compared with those patients who were persistently p24-negative (relative risk 7.24; P less than 0.0001, Cox proportional hazards model). The relative risk was reduced to 5.42 (P less than 0.0001) after adjustment for age and cytomegalovirus seropositivity. After adjustment for the patients' declining CD4 lymphocyte count during follow-up, the relative risk fell dramatically to 1.97 and became non-significant (P = 0.2). p24-antigenaemic patients tended to develop AIDS at levels of similar CD4 lymphocyte counts to those who were persistently p24-antigen-negative (median CD4 lymphocyte counts, 70 and 50 x 10(6)/l, respectively). These results suggests that the association between p24 antigenaemia and the rate of progression to AIDS can be explained largely by a more rapid decline in CD4 lymphocyte count among patients with p24 antigenaemia than in those without. The major pathological effects of increased plasma viral load, as detected by the presence or absence of p24 antigenaemia, appear to act via progressive CD4 lymphocyte depletion.