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1.
To determine if the early immunological and virological events of HIV infection are unique in a setting with limited access to health care and HIV-1 subtype C infection, we undertook a prospective cohort study to characterize the early natural history of HIV viral load and CD4(+) T lymphocyte counts in individuals with recent HIV seroconversion in India. CD4(+) T lymphocyte counts were prospectively measured for up to 720 days in 46 antiviral drug-naive persons with very early HIV infection, documented by HIV antibody seroconversion. HIV viral RNA levels were measured subsequently on reposited plasma samples from these same time points. The median viral load "set point" for Indian seroconverters was 28,729 RNA copies/ml. The median CD4(+) cell count following acute primary HIV infection was 644 cells/mm(3). Over the first 2 years since primary infection, the annual rate of increase in HIV viral load was +8274 RNA copies/ml/year and the annual decline in CD4 cell count was -120 cells/year. Although the viral "set point" was similar, the median trajectory of increasing viral load in Indian seroconverters was greater than what has been reported in untreated HIV seroconverters in the United States. These data suggest that the more rapid HIV disease progression described in resource-poor settings may be due to very early virological and host events following primary HIV infection. A rapid increase in viral load within the first 2 years after primary infection may have to be considered when applying treatment guidelines for antiretroviral therapy and opportunistic infection prophylaxis.  相似文献   

2.
The majority of natural history studies of human immunodeficiency virus (HIV) infection have immune and viral parameters in men. Data demonstrating that women have lower HIV-1 RNA levels than men at the same CD4 cell counts have raised the question of immunologic differences in HIV-seropositive women. This study describes levels and changes in phenotypic markers of immune maturity, function, and activation in the CD4 and CD8 cell subsets in HIV-seropositive and high-risk HIV-seronegative women. Our primary hypothesis was that activation levels would be significantly higher among illicit drug users. However, results showed that HIV-1 RNA level was the strongest predictor of marker level and that both HIV-1 RNA level and CD4 cell count were independently associated with CD4 activation, but illicit drug use was not. In summary, this study demonstrated that immune activation was a significant pathogenic feature in women and that activation was driven by HIV infection and not illicit drug use.  相似文献   

3.
This report examines the relationship between substance use, psychosocial stressors, and natural killer (NK) cell enumeration and function in HIV-infected and high-risk uninfected adolescents. We studied the association of demographic characteristics; self-report measures of alcohol, tobacco, and marijuana use; and self-report measures of psychosocial stressors (depressive symptoms, anxiety) with three immune outcomes: NK (CD3(-)CD16(+)CD56(+)) absolute counts, lytic units per peripheral blood mononuclear cells (PBMCs), and lytic units per NK cell. In addition, we determined the association of HIV disease stage, antiretroviral therapy (ART), CD4(+) T-cell count, and viral load with these outcomes in the subset of HIV-infected adolescents. METHODS: This cross-sectional analysis reports on data collected during a longitudinal observational study of adolescents (the REACH Study). A cross-sectional analysis was performed with data from the first visit for each subject that met criteria for concurrent (within 3 days) assessment of NK number and function, substance use, and psychosocial data. The data set represented 501 subjects. Analyses were performed separately for the HIV-seropositive and seronegative adolescents. In the HIV-seronegative population, there were no significant predictors of NK cell count and only female gender was significantly associated with CD3(-)CD16(+)CD56(+) NK lytic units per PBMC. Analysis of the HIV-seronegative cohort also showed that black race was significantly associated with higher lytic units per NK cell. RESULTS: In HIV-seropositive adolescents, we observed an association of female gender with lower NK cell number and lytic units per PBMC, but not with lytic units per NK cells. Current use of one or two antiretroviral drugs was predictive of lower NK numbers. This drug effect was also noted in the functional assay per PBMC but not per NK cell. Increasing worry scores and no marijuana use over the past 3 months were associated with lower functional NK measures per PBMC in HIV-seropositive youth. Laboratory-confirmed recent marijuana use was highly predictive of increased lytic activity calculated per NK cell. These effects were not observed in similar analyses of data from HIV-seronegative adolescents. Depressive symptoms, assessed with an epidemiologic screening tool, were not found to be predictive of NK cell number or function in either the HIV-seronegative or the HIV-seropositive subset. These findings document associations between substance abuse, psychosocial variables, and NK numbers and function in adolescents.  相似文献   

4.
OBJECTIVES: In order to evaluate the role played by cytokine profile as a co-factor involved in the resistance to HIV infection in couples serodiscordant for HIV, we studied HIV-seronegative subjects with multiple unprotected sexual exposures. DESIGN AND METHODS: Twenty-one HIV-exposed seronegative subjects (HEPS), their 21 HIV-seropositive partners and 10 HIV-seronegative unexposed individuals were studied for T helper (Th) types 1-2 cell pattern and CCR5 receptor. RESULTS: Twelve out of 21 HIV-seropositive partners of HEPS showed a CD4 cell count below 200 lymphocytes/microl. HIV strains were isolated from peripheral blood mononuclear cells (PBMC) in 17 patients (81%): seven subjects with syncytium-inducing strains and 10 with non-syncytium-inducing isolates. Low Th1 cytokine production and high levels of IL-4 were detected in HIV-seropositive subjects. A significant reduction of IL-2 and IFN-gamma expression in the CD4 and CD8 cells of HEPS was found compared with HIV-seronegative unexposed individuals. Similar levels of low IL-4 were present in both HEPS and controls. The partial deletion of a single allele (wild type/delta32) of CCR5 was found in only one HEPS. CONCLUSION: The downregulated Th1 profile we observed in HEPS could be related to a cellular anergy state with a protective role in the transmission rate of HIV. Low levels of IL-2 and IFN-gamma could be involved in a low-grade activation state of CD4 lymphocytes. A decrease of IFN-gamma levels could render macrophage cells incapable of antigen presentation, thus resulting in a reduction of the cell-to-cell spread of infection.  相似文献   

5.
We examined incidence and correlates of progression and regression of abnormal cervical cytologic test results, defined as at least low-grade squamous intraepithelial lesions (SILs), in 774 human immunodeficiency virus (HIV)-seropositive and 391 HIV-seronegative women monitored semiannually for up to 5.5 years. During follow-up, 224 (35%) HIV-seropositive women and 34 (9%) HIV-seronegative women had incident SILs detected by Pap test; 47 (7%) HIV-seropositive women developed high-grade lesions. The incidence of SILs was 11.5 cases among HIV-seropositive and 2.6 cases among HIV-seronegative women per 100 person-years of observation (rate ratio, 4.5; 95% confidence interval, 3.1-6.4; P<.001). Risk of incident SILs and likelihood of Pap test progression were increased among HIV-seropositive women with CD4(+) lymphocyte counts <500 cells/mm(3) and among women with human papillomavirus (HPV) infection, with risk-ordering from low- to high-risk HPV type. SIL regression was less likely among HIV-seropositive women with higher HIV loads. No beneficial effect of highly active antiretroviral therapy was demonstrated.  相似文献   

6.
Five HIV-seropositive twins were treated with HAART and given cycles of treatment consisting of adoptive cellular therapy from their HIV-seronegative identical twins followed by a 5-day course of intravenous IL-2. Changes in absolute and percent CD4(+) and CD8(+) cell count were monitored and compared with changes in these parameters occurring in seven age-, sex-, and disease stage-matched HIV-infected patients treated with HAART alone. Increase in the magnitude and breadth of HIV-specific immune responses was monitored in three twin subjects who received multiple treatment cycles. Absolute and percent CD4(+) cell counts rose dramatically and to significantly higher levels in the recipient twins than in control subjects treated with HAART only. The subjects who received multiple cycles of treatment developed new and increased levels of HIV-specific activated and memory cytotoxic T lymphocyte responses, and interferon gamma-secreting effector cells. Treatment consisting of HAART, adoptive cellular therapy, and IL-2 was superior to treatment with HAART alone for improving absolute and percent CD4(+) cell counts and inducing new, or increasing the magnitude of, HIV-specific immune responses in HIV infected patients.  相似文献   

7.
The relationship of serum human immunodeficiency virus-1 (HIV-1) RNA levels to HIV-1 RNA levels in other compartments, such as the lungs, is not well characterized. The purpose of this study was to determine the viral burden of HIV-1 in the lungs by comparing HIV-1 RNA in cell-free bronchoalveolar lavage fluid (BALF) with that in serum. Specimens were examined from 77 HIV-seropositive adults (CD4(+) cell counts: 0 to 700 cells/mm(3); 48% receiving prescribed antiretroviral agents), comprising 43 asymptomatic individuals who were compared with 34 persons with active lung disease caused by Pneumocystis carinii (n = 26), bacteria (n = 3), Mycobacterium avium complex (n = 2), Nocardia sp. (n = 1), Aspergillus sp. (n = 1), or pulmonary Kaposi's sarcoma (n = 1). For serum HIV-1 RNA, the proportion of subjects with detectable levels and the mean values were similar for asymptomatic individuals and persons with active lung disease (85% versus 86%, respectively) (6.64 x 10(4) versus 1. 81 x 10(5) HIV-1 RNA copies/ml; p = 0.13). In contrast, HIV-1 RNA in BALF was more often detected (16% versus 62%; p = 0.001), and mean values were higher (1.04 x 10(5) versus 3.31 x 10(6) HIV-1 RNA copies/ml; p = 0.032), in subjects with active lung disease than in asymptomatic subjects, independent of early or advanced clinical stages of HIV-related disease. For both study groups, HIV-1 RNA levels in BALF exceeded those in serum in 56% of cases by up to 66-fold, and did not correlate with local levels of tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, or interleukin-16. HIV-1 proviral DNA in cells from BALF was detected in up to 86% of subjects, more frequently in persons with advanced HIV disease (p = 0.0496), and often involved > 10% of BALF cells, but did not correlate with HIV-1 RNA detected in BALF. These data provide evidence for active HIV-1 replication in the lungs. HIV-1 replication is compartmentalized relative to serum, may be restricted, is independent of HIV-1 proviral DNA and clinical stage of HIV, and may be influenced by pulmonary disease such as P. carinii pneumonia or by other local or lung-specific factors. The lungs represent a large reservoir for HIV-1, and may present a source of persistent HIV-1 replication even during periods of apparent clinical latency of HIV-1 infection.  相似文献   

8.
Kaposi's sarcoma-associated herpesvirus (KSHV) DNA, consistently found in Kaposi's sarcoma (KS) tissues, was sought in peripheral blood mononuclear cells (PBMCs) of HIV-infected individuals. To determine quantitative relationships between the presence of KSHV DNA in PBMCs, CD4 cell counts, plasma HIV RNA levels, and the development of KS, we designed a cross-sectional study of prospectively collected PBMC samples from ongoing cohort studies. PBMCs were collected from 142 HIV-seropositive individuals in California, 7 of whom had a clinical diagnosis of KS. KSHV sequences were detected in extracted PBMC DNA by nested polymerase chain amplification using two nonoverlapping primer sets. KSHV DNA was detected in PBMCs of 5 of 7 (71%) subjects with KS and in 18 of 135 (13%) HIV-infected subjects without KS. Among HIV-seropositive individuals without KS, detection of KSHV was more common in men than women (19 versus 4%, p = 0.01) and was associated with lower mean CD4 percent (14.8 versus 20.7% CD4 cells, p = 0.03), lower mean CD4 cell count (244 versus 334 CD4 cells/microl, p = 0.05), and higher geometric mean plasma HIV RNA (4.83 versus 4.03 1og10 copies/ml, p = 0.0002). Semiquantitative analysis found 5 to 15,625 copies of KSHV per microgram of PBMC DNA with increased plasma HIV RNA levels and a trend toward increased subsequent development of KS in subjects with higher KSHV loads. The association of the presence of KSHV DNA in PBMCs with lower CD4 cell counts and higher plasma HIV RNA provides evidence of a relationship between immunosuppression, HIV replication, and KSHV expression.  相似文献   

9.
10.
HIV infection is characterized by CD4(+) T cell depletion and progressive immune dysfunction; particularly impacted are HIV-specific T cell responses. An important component of immune-mediated control of HIV replication, killing of infected cells, appears to be impaired, in part due to poor cytolytic activity of HIV-specific cytotoxic T cells (CTL). In vitro, several functions of HIV-specific T cells, such as cytokine production, can be enhanced by the depletion of the immunosuppressive CD25(+) FoxP3(+) CD4(+) regulatory (Treg) cell subset. However, the effect of CD25(+) Treg cells on virus-specific cytolytic activity in the context of HIV or any human viral infection has not been investigated. The present study demonstrates that CD25(+) Treg cells isolated from the peripheral blood of HIV-infected subjects significantly suppress HIV Gag-specific cytolytic activity in vitro. In addition, CD25(+) Treg cells suppress effector function (coexpression of TNF-alpha and IFN-gamma) of HIV-specific CD8(+) T cells that proliferate in response to HIV antigen. Finally, the secretion of HIV-inhibitory CC-chemokines by HIV-specific and nonspecific CD8(+) T cells is significantly reduced in the presence of CD25(+) Treg cells. These data suggest that CD25(+) Treg-mediated suppression of the antiviral activity of HIV-specific CD8(+) T cells could impact the ability of HIV-infected individuals to control HIV replication in vivo.  相似文献   

11.
We assessed the frequency and distribution of infection with opportunistic and non-opportunistic intestinal parasites and the liver fluke, Opisthorchis viverrini, in HIV-seropositive and HIV-seronegative subjects. Age- and sex-matched HIV-seropositive (n = 78) and HIV-seronegative patients (n = 78) from two hospitals in Khon Kaen Province, Thailand, participated in this study from November 1998 to August 2000. These subjects were divided according to the presence of diarrhea and CD4 counts. A single stool sample was obtained and analyzed by using specific techniques. Opisthorchis viverrini, was the most common parasite (19.2%) in each group. The prevalence rates of Cryptosporidium spp (11.5%) and Strongyloides stercoralis (17.9%) in the HIV-seropositive group were significantly (p < 0.05) higher than those in the HIV-seronegative group (1.0% for Cryptosporidium spp and 7.7% for S. stercoralis infections). The prevalences of these two parasites were 28% for Cryptosporidium spp and 20% for S. stercoralis in HIV-seropositives with diarrhea and CD4 counts lower than 100 cells/mm3, and were higher compared with patients without diarrhea or with high CD4 counts. These results suggest that infection with these parasites increases during HIV infection. The epidemiological distribution of Cryptosporidium and S. stercoralis may have implications for AIDS-related diseases.  相似文献   

12.
Although T cell activation is associated with disease progression in untreated human immunodeficiency virus type 1 (HIV-1) infection, its significance in antiretroviral-treated patients is unknown. Activated (CD38(+)HLA-DR(+)) T cell counts were measured in 99 HIV-infected adults who had maintained a plasma HIV RNA level 相似文献   

13.
OBJECTIVES: To determine the association between invasive cervical cancer (ICC) and HIV infection in Kenyan women. STUDY DESIGN: Case-control, with ICC patients as cases, and women with uterine fibroids as controls. METHODS: Medical and socio-demographic data were collected from 367 ICC patients, and 226 women with fibroids. After informed consent, HIV testing was done. RESULTS: ICC patients were older than fibroid patients (48 versus 41 years; P < 0.001), with an HIV seroprevalence of 15% and 12% respectively (P > 0.05). However, cases younger than 35 years were 2.6-times more likely to be HIV positive than controls of similar age [35% versus 17%; odds ratio (OR), 2.6; P = 0.043]. ICC HIV-seropositive patients were, on average, 10 years younger than HIV-seronegative patients (40 versus 50 years; P < 0.001). Eighty per cent of HIV-seropositive and 77% of HIV-seronegative ICC patients were in FIGO stage IIb or above. However, the odds of having poorly differentiated tumours was three times higher for HIV-seropositive than for HIV-seronegative ICC patients (77% versus 52%; OR, 3.1; P = 0.038) after adjusting for histological cell type and clinical stage. Mean CD4 cell count was 833 x 10(6) cells/l in ICC and 1025 x 10(6) cells/l in fibroid patients (P = 0.001). CONCLUSION: Young women with ICC were more often HIV infected than women with fibroids of the same age groups. HIV infection was associated with poor histological differentiation of the tumours. These findings suggest an accelerated clinical progression of premalignant cervical lesions to ICC in HIV-infected women.  相似文献   

14.
SETTING: In persons infected with the human immunodeficiency virus (HIV), a decreased tuberculin reaction cut-point of > or = 5 mm induration is recommended. OBJECTIVE: To determine tuberculosis risk in non-anergic HIV-infected persons with 5-9 mm tuberculin reactions. DESIGN: A prospective study with semi-annual tuberculin and anergy testing, HIV antibody and T cell subset assays, and active surveillance for tuberculosis. RESULTS: Participants were 572 HIV-seronegative and 241 HIV-seropositive non-anergic drug users. No tuberculosis occurred in HIV-seronegative persons. Tuberculosis incidence among HIV-seropositive drug users was 3.3, 7.7, 0, and 0.34 per 100 person-years in those with tuberculin reaction sizes of > or = 10 mm, 5-9 mm, 1-4 mm, and 0 mm, respectively, and was significantly increased in persons with 5-9 mm induration compared with those with 0-4 mm induration (rate ratio 27.7, 95%CI 2.9-268). Among persons with reaction sizes of 5-9 mm, tuberculosis occurred exclusively in those with CD4+ lymphocyte counts <500/mm3 at the time of their 5-9 mm tuberculin reactions. CONCLUSION: HIV-infected persons with tuberculin reaction sizes of 5-9 mm are at increased risk for tuberculosis compared to non-anergic persons with smaller (0-4 mm) reaction sizes. However, this increased risk may be limited to those with low CD4+ lymphocyte counts at the time of tuberculin testing.  相似文献   

15.
The presence of immunoreactivity to the neuronal phosphoprotein B-50 and the peptides bombesin, calcitonin gene-related peptide, galanin, neurotensin, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal polypeptide was examined in biopsy specimens from the duodenum and rectum of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative male homosexual patients. The distribution of B-50 and the peptides was correlated with HIV serology, number of CD4+ lymphocytes, and the presence of HIV in biopsy culture. There was a very low incidence of enteric pathogens in both groups of patients. It was found that HIV-seropositive patients had a greater incidence of abnormal patterns of immunoreactivity (reduced intensity and/or density of innervation) in enteric nerves and enteroendocrine cells than HIV-seronegative patients. A reduction of substance P immunoreactivity was significantly correlated with reduced CD4+ lymphocyte count and HIV status; a similar trend was also seen for somatostatin and vasoactive intestinal polypeptide. Using B-50 as a marker, it was found that both groups of patients had altered patterns of immunoreactivity in rectal nerves. The findings of this study suggest that some of the clinical symptoms associated with HIV infection may be caused by a specific HIV enteropathy that influences enteric nerve and/or enteroendocrine cell function by altering the density of peptide immunoreactivity.  相似文献   

16.
BACKGROUND: The optimal time to initiate highly active antiretroviral therapy (HAART) remains unclear. METHODS: Five hundred eighty-three human immunodeficiency virus (HIV)-seropositive and 920 HIV-seronegative injection drug users (IDUs) were followed from 1997 to 2000. HIV-seropositive participants were categorized according to receipt of HAART (either initiated or switched to HAART) and initial CD4 cell count. Survival analysis that included delayed-entry and Cox proportional-hazards models was used to evaluate the effect of HAART, with adjustments for factors associated with access to HAART. RESULTS: Compared with HIV-seronegative participants, overall survival was similar in HIV-seropositive participants who received HAART at >350 CD4 cells/microL, but mortality was higher both in participants with >350 CD4 cells/microL who did not receive HAART and in participants who received HAART at 200-350 CD4 cells/microL (mortality rates, 19.9, 24.0, 43.0, and 50.5/1000 person-years, respectively). In proportional-hazards models in which HIV-seronegative participants were the reference group and in which age, sex, race, frequency of drug use, substance-abuse treatment, and health-care utilization were adjusted for, hazard ratios were 1.01 (95% confidence interval [CI], 0.41-2.45), 2.28 (95% CI, 1.38-3.78), and 2.09 (95% CI, 1.07-4.10) for the latter 3 groups. In HIV-seropositive participants, HAART significantly improved survival when initiated at CD4 cell counts < 200 cells/microL. CONCLUSIONS: Survival of HIV-seropositive participants receiving HAART approximated that of HIV-seronegative participants only when therapy was given at CD4 cell counts > 350 cells/microL. These data, restricted to IDUs, suggest initiating or switching to HAART at higher CD4 cell levels than are currently recommended.  相似文献   

17.
Summary . Twenty-four of 117 cases of haemophilia A (20.5%) and none of 18 cases of haemophilia B reported in this study had an antibody to the human immuno-deficiency virus (HIV). Both groups of patients showed similar immunological alterations. HIV-seropositive haemophilia A patients had an increased CD8 cell count and a similarly decreased CD4/CD8 ratio as compared to HIV-seronegative haemophilia A patients. Multiple regression analysis for the association of CD4/CD8 ratio with HIV infection status and dosage of plasma products in haemophilia A and B patients, respectively, revealed that there was a significant negative association of ln(CD4/CD8) with dosage of factor VlII concentrates (P = 0.0435) and factor IX concentrates (P = O.O028), respectively. N o association occurred between CD4/CD8 ratio and HIV infection as well as dosage of other plasma products. These data indicate that the immunological abnormalities of our haemophilia A and B patients in their early years were primarily caused by various viral infections and/or a suppressive effect of allogeneic protein through infusion of factor concentrates and not caused simply by HIV infection.  相似文献   

18.
Lymph nodes constitute the major site of HIV replication and of immunological response to HIV. To study the role of cytotoxic and mitotic active CD8(+) lymphocytes in lymph nodes during HIV infection we examined 28 formalin-fixed, paraffin-embedded lymph nodes sampled from 1984 to 1986 from 21 HIV-seropositive patients and seven HIV-negative patients. Eleven of the HIV-positive patients died within 78 months of biopsy time and 10 patients were alive on July 1, 1998. Double immunohistochemical staining procedures were developed to identify CD8(+) cells expressing CD45R0, granzyme B, and Ki-67. A stereological method was used to count the different cell types in the lymph nodes. There were no significant differences in the total cell (nucleated) and CD3(+) cell concentrations between the three groups. However, there were significantly higher concentrations of CD3(+)CD8(+), CD8(+)CD45R0(+), and CD8(+)Ki-67(+) lymphocytes in the HIV patients compared with the control group. Furthermore, there was a tendency for the HIV-deceased group to have lower levels of CD8(+)granzyme B(+) and CD8(+)Ki-67(+) lymphocyte concentrations compared with the HIV-alive group. Three HIV patients, who progressed to death within 49 months of biopsy time, were among the patients with the lowest concentrations of CD8(+)granzyme B(+) and CD8(+)Ki-67(+) lymphocytes. This finding allowed us to conclude that CD8(+) lymphocytes expressing high levels of CD45R0, granzyme B, and Ki-67 in lymph nodes of HIV patients are not related to increased mortality, whereas low concentrations of CD8(+) granzyme B(+) and CD8(+)Ki-67(+) lymphocytes may be associated with poor prognosis.  相似文献   

19.
Lymphadenitis is a common extrapulmonary manifestation of mycobacterial disease in persons with human immunodeficiency virus (HIV) infection. We compared the clinical, mycobacterial, and diagnostic characteristics of mycobacterial adenitis in 11 HIV-seropositive and 29 HIV-seronegative patients. Ninety-three percent of the HIV-seronegative patients and 54% of the HIV-seropositive patients were foreign-born. In contrast to the HIV-seronegative patients, seropositive patients were more likely to be febrile and have negative purified protein derivative skin tests and abnormal chest roentgenograms. Sputum samples were rarely diagnostic in either group. Mycobacterium tuberculosis was the most commonly isolated organism in both groups, although United States-born patients with HIV infection were more likely to be infected with nontuberculous mycobacteria. In contrast to results for seronegative patients, fine-needle aspiration was usually diagnostic in the HIV-seropositive population, especially in those at risk for M. tuberculosis infection. Similarly, the rate at which smears were positive for acid-fast bacilli was significantly higher in the HIV-seropositive group, a circumstance suggesting a higher burden of organisms in this population. Finally, although preceding opportunistic infections were uncommon in the HIV-seropositive group, both tuberculous and nontuberculous adenitis were associated with advanced immunosuppression.  相似文献   

20.
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