An exploratory trial of cyclooxygenase type 2 inhibitor in HIV-1 infection: downregulated immune activation and improved T cell-dependent vaccine responses.

Chronic HIV infection is characterized by chronic immune activation and dysfunctional T cells with elevated intracellular cyclic AMP (cAMP), which inhibits the T cell activation capability. cAMP may be induced by prostaglandin E(2) following lipopolysaccharide (LPS)-induced upregulation of cyclooxygenase type 2 (COX-2) in monocytes due to the elevated LPS levels in patients with chronic HIV infection. This hypothesis was tested using celecoxib, a COX-2 inhibitor, for 12 weeks in HIV-infected patients without antiretroviral treatment in a prospective, open, randomized exploratory trial.

Distinct mechanisms for mitochondrial DNA loss in T and B lymphocytes from HIV-infected patients exposed to nucleoside reverse-transcriptase inhibitors and those naive to antiretroviral treatment.

Objective: Mitochondrial DNA (mtDNA) loss in peripheral blood mononuclear cells (PBMCs) has been found in both nucleoside reverse-transcriptase inhibitor (NRTI)-exposed and antiretroviral therapy (ART)-naive patients with human immunodeficiency virus (HIV) infection. Persistent immune activation might play a role in this phenomenon in HIV-infected, ART-naive patients. PBMC subsets with differential growth kinetics were therefore purified to study this similarity.

PD-1 predicts CD4 loss rate in chronic HIV-1 infection better than HIV RNA and CD38 but not in cryopreserved samples.

The immunopathogenic factor programmed cell death 1 (PD-1) was compared to CD38 and HIV RNA in predicting actual CD4+ T cell loss rate indicative for clinical progression. This cross sectional exploratory study included 50 consecutive, healthy HIV-infected patients off antiretroviral therapy (ART); 43 had the required observation times > 12 months. PD-1 and CD38 were determined on various T cell subsets by FACS analyses in fresh and later in parallel cryopreserved samples.