Impact of CMV therapy with valganciclovir on immune activation and the HIV viral load in semen and blood: an observational clinical study.

Background: The HIV RNA viral load (VL) in vaginal secretions and semen is an independent predictor of HIV transmission. Blood VL is associated with semen VL, and local mucosal factors, such as semen cytomegalovirus (CMV) reactivation, may play an important role.

Methods: Twenty-one HIV-CMV-coinfected, antiretroviral-naive men received 900 mg of oral valganciclovir once daily for 2 weeks in an open-label study.

Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expression.

Recent data suggest that CD8+ T-cell effector activity is an important component in the control of HIV replication in elite controllers (ECs). One critical element of CD8+ T-cell effector function and differentiation is the T-box transcription factor T-bet. In the present study, we assessed T-bet expression, together with the effector proteins perforin, granzyme A (Grz A), granzyme B (Grz B), and granulysin, in HIV-specific CD8+ T cells from ECs (n = 20), chronically infected progressors (CPs; n = 18), and highly active antiretroviral therapy (HAART)-suppressed individuals (n = 19).

Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control.

Many immune correlates of CD8(+) T-cell-mediated control of HIV replication, including polyfunctionality, proliferative ability, and inhibitory receptor expression, have been discovered. However, no functional correlates using ex vivo cells have been identified with the known ability to cause the direct elimination of HIV-infected cells. We have recently discovered the ability of human CD8(+) T-cells to rapidly upregulate perforin--an essential molecule for cell-mediated cytotoxicity--following antigen-specific stimulation.

Relative HIV resistance in kenyan sex workers is not due to an altered prevalence or mucosal immune impact of herpes simplex virus type 2 infection.

Chronic infection by herpes simplex virus type 2 (HSV-2) increases HIV susceptibility, perhaps due to HSV-2-associated increases in activated mucosal immune cells. A small number of Kenyan female sex workers (FSWs) exhibit relative HIV resistance. We examined whether relative HIV resistance was related to differences in the prevalence or mucosal immune impact of HSV-2.

Mucosal Neisseria gonorrhoeae coinfection during HIV acquisition is associated with enhanced systemic HIV-specific CD8 T-cell responses.

Background: The host immune response against mucosally acquired pathogens may be influenced by the mucosal immune milieu during acquisition. As Neisseria gonorrhoeae can impair dendritic cell and T-cell immune function, we hypothesized that coinfection during HIV acquisition would impair subsequent systemic T-cell responses.

Methods: Monthly screening for sexually transmitted infections was performed in high risk, HIV seronegative Kenyan female sex workers as part of an HIV prevention trial.

Coinfection with herpes simplex virus type 2 is associated with reduced HIV-specific T cell responses and systemic immune activation.

Background: Chronic coinfection with herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) has been associated with an increased HIV viral load and more rapid disease progression, perhaps related to HSV-2-associated alterations in host immunity.

Methods: Studies were nested within (1) a cross-sectional study of men coinfected with HIV and HSV-2 and (2) women not infected with HIV, both before and after HSV-2 acquisition. HSV-2 infection status was determined by ELISA.

Effects of the chemotherapeutic agent doxorubicin on the protein C anticoagulant pathway.

Although chemotherapy treatment is associated with an increased risk of thrombosis, the pathogenic mechanisms for the thrombogenic effect of chemotherapeutic drugs are poorly understood. We hypothesize that exposure of vascular endothelial cells to chemotherapeutic agents results in the loss of a thromboresistant phenotype. In this study, we examined the effects of the chemotherapeutic agent doxorubicin on the endothelium-based protein C anticoagulant pathway.

Activated protein C in sepsis and beyond: update 2006.

Activated protein C (APC), a plasma serine protease, is best known for its ability to inhibit blood clot formation. APC acts as an anticoagulant by degrading coagulation cofactors Va and VIIIa, thereby attenuating the coagulation cascade. Over the past 15 years, impressive research advances have provided novel insights into the diverse biological activities of this molecule.