Longitudinal Analysis of Quantitative Virologic Measures in Human Immunodeficiency Virus-Infected Subjects with >=400 CD4 Lymphocytes: Implications for Applying Measurements to Individual Patients

SummaryIn human plasma, heparin cofactor II (HCII) is a thrombin inhibitor, whose deficiency has been reported to be associated with recurrent thrombosis. The finding of two cases of low plasma HCII activity in two patients infected with the human immunodeficiency virus (HIV) led us to investigate this coagulation inhibitor in the plasma of a larger population of HIV-infected patients. The mean plasma HCII activity was significantly lower in 96 HIV-infected patients than in 96 age- and sex-matched healthy individuals (0.75 ± 0.24 vs 0.99 ± 0.17 U/ml, p <0.0001). HCII antigen concentration was decreased to the same extent as the activity. The proportion of subjects with HCII deficiency was significantly higher in the HIV-infected group than in healthy individuals (38.5% vs 2.1%). In addition, HCII was significantly lower in AIDS patients than in other HIV-infected patients, classified according to the Centers for Disease Control (CDC) on the basis of an absolute number of circulating CD4+ lymphocytes below 200 x 106/1. The link between HCII and immunodeficiency is further suggested by significant correlations between HCII activity and both the absolute number of CD4+ lymphocytes and the CD4+ to CD8+ lymphocyte ratio. Nevertheless, the mean HCII level was not different in the various groups of patients classified according to clinical criteria, except in CDC IVD patients in whom HCII levels were significantly lower. In addition, no correlation could be demonstrated between HCII and protein S activities, another coagulation inhibitor whose plasma level was also found to be decreased in HIV-infected patients. A similar prevalence of HCII deficiency was also found in a small series of 7 HIV-infected patients who developed thrombotic episodes, an unusual complication of the infection. This suggests that, in HIV-infected patients, HCII deficiency is not in itself the causative factor for the development of thrombosis.

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LONGITUDINAL ANALYSIS OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 RNA IN BREAST MILK AND OF ITS RELATIONSHIP TO INFANT INFECTION AND MATERNAL DISEASE

PEDIATRICS ◽

10.1542/peds.114.2.s1.552-a ◽

2004 ◽

Vol 114 (2) ◽

pp. 552-552

Author(s):

J. A. Church

Keyword(s):

Human Immunodeficiency Virus ◽

Breast Milk ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Longitudinal Analysis ◽

Immunodeficiency Virus ◽

Maternal Disease

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In vitro antioxidant treatment recovers proliferative responses of anergic CD4+ lymphocytes from human immunodeficiency virus-infected individuals

Blood ◽

10.1182/blood.v87.11.4746.bloodjournal87114746 ◽

1996 ◽

Vol 87 (11) ◽

pp. 4746-4753 ◽

Cited By ~ 30

Author(s):

A Cayota ◽

F Vuillier ◽

G Gonzalez ◽

G Dighiero

Keyword(s):

Human Immunodeficiency Virus ◽

Cell Death ◽

Programmed Cell Death ◽

Redox Status ◽

Therapeutic Strategies ◽

Antioxidant Treatment ◽

Immunodeficiency Virus ◽

Cd4 Lymphocytes ◽

Cellular Thiol

Oxidative stress has been proposed to be involved in the immunologic defeat observed in effector calls of the immune system as well as in lymphocyte cell death and viral replication in human immunodeficiency virus (HIV)-infected patients. Because thiol-containing antioxidants such as N-acetyl-L-cysteine have been shown to have beneficial effects on CD4+ lymphocyte survival and to inhibit programmed cell death and HIV-1 replication, they may play a role in therapeutic strategies of this disease. In this work we have studied the cellular thiol levels and the affect of in vitro antioxidant treatment of purified CD4+ lymphocytes from HIV-infected patients, and correlated these parameters to proliferative responses and programmed cell death. We show that CD4+ lymphocytes from HIV-infected patients display impaired proliferative responses and a significant decrease in cellular thiol levels, indicating a disturbed redox status. Interestingly, antioxidant treatment succeeded to restore defective proliferative responses to CD3- mediated activation in 8 of 11 patients (high antioxidant responders). In contrast to high responders, patients failing to respond to antioxidant treatment (low antioxidant responders), were characterized by an abnormal ratio of apoptotic cells, which was not affected by N- acetyl-L-cysteine and/or 2-beta-mercaptoethanol preincubation. These results demonstrate for the first time that antioxidant treatment is able to revert the impaired proliferative activity of CD4 cells from HIV-infected patients and could help designing therapeutic strategies with antioxidant drugs. However, this action is not observed in cells undergoing programmed cell death.

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