Baseline levels of soluble CD14 and CD16+56- natural killer cells are negatively associated with response to interferon/ribavirin therapy during HCV-HIV-1 coinfection.

Disease progression of human immunodeficiency virus type 1 (HIV-1) is associated with immune activation. Activation indices are higher during coinfection of hepatitis C virus (HCV) and HIV. The effect of immune activation on interferon α (IFN-α) therapy response is unknown.

Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells.

Background: Failure to normalize CD4(+) T-cell numbers despite effective antiretroviral therapy is an important problem in human immunodeficiency virus (HIV) infection.

Methods: To evaluate potential determinants of immune failure in this setting, we performed a comprehensive immunophenotypic characterization of patients with immune failure despite HIV suppression, persons who experienced CD4(+) T-cell restoration with therapy, and healthy controls.

Results: Profound depletion of all CD4(+) T-cell maturation subsets and depletion of naive CD8(+) T cells was found in immune failure, implying failure of T-cell production/expansion.

Circulating human CD4 and CD8 T cells do not have large intracellular pools of CCR5.

CC Chemokine Receptor 5 (CCR5) is an important mediator of chemotaxis and the primary coreceptor for HIV-1. A recent report by other researchers suggested that primary T cells harbor pools of intracellular CCR5. With the use of a series of complementary techniques to measure CCR5 expression (antibody labeling, Western blot, quantitative reverse transcription polymerase chain reaction), we established that intracellular pools of CCR5 do not exist and that the results obtained by the other researchers were false-positives that arose because of the generation of irrelevant binding sites for anti-CCR5 antibodies during fixation and permeabilization of cells.

Uridine supplementation in the treatment of HIV lipoatrophy: results of ACTG 5229.

Background: Lipoatrophy is prevalent on thymidine nucleoside reverse transcriptase inhibitors (tNRTIs). A pilot trial showed that uridine (NucleomaxX) increased limb fat.

Methods: A5229 was a multicenter trial in which HIV-infected individuals with lipoatrophy on tNRTI regimens were randomized to NucleomaxX or placebo.

The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: a randomized controlled trial.

Background: Most HIV-1-infected patients on effective antiretroviral therapy (ART) with plasma HIV-1 RNA levels below the detection limits of commercial assays have residual viremia measurable by more sensitive methods. We assessed whether adding raltegravir lowered the level of residual viremia in such patients.

Methods And Findings: Patients receiving ART who had plasma HIV-1 RNA levels below 50 copies/mL but detectable viremia by single copy assay (SCA) were randomized to add either raltegravir or placebo to their ART regimen for 12 weeks; patients then crossed-over to the other therapy for an additional 12 weeks while continuing pre-study ART.

In vitro naïve T cell proliferation failure predicts poor post-immunization responses to neoantigen, but not recall antigens, in HIV-infection.

Immune reconstitution after HAART is incomplete, but no widely accepted method to quantify subclinical immune deficiency is available. We immunized 9 HIV-negative subjects and 29 HIV-infected patients with CD4>/=450 cells/microL and undetectable HIV RNA levels with 2 doses of diphtheria/tetanus toxoid (TT) and KLH, a presumed neoantigen. We quantified the response by lymphoproliferative assay, delayed-type hypersensitivity (DTH), and antibody titers up to 59days after enrollment.

IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection.

Interleukin 7 (IL-7) is a common gamma chain receptor cytokine implicated in thymopoiesis and in peripheral expansion and survival of T lymphocytes. The safety and activity of recombinant human IL-7 (rhIL-7) administration were therefore examined in HIV-infected persons. In this prospective randomized placebo-controlled study, a single subcutaneous dose of rhIL-7 was well tolerated with biologic activity demonstrable at 3 microg/kg and a maximum tolerated dose of 30 microg/kg.

Cyclosporin A provides no sustained immunologic benefit to persons with chronic HIV-1 infection starting suppressive antiretroviral therapy: results of a randomized, controlled trial of the AIDS Clinical Trials Group A5138.

Background: Although the determinants of immune deficiency and immune restoration in chronic human immunodeficiency virus (HIV)-1 infection are not well understood, immune activation has been proposed as being central to the pathogenesis of HIV.

Methods: A randomized, controlled trial of cyclosporin A treatment for 2 weeks was performed in persons with chronic HIV-1 infection who were beginning a standardized antiretroviral therapy (ART) regimen.

Results: Treatment with cyclosporin A provided only a marginal and transient enhancement in circulating T cell restoration that was largely restricted to cells expressing the CCR7 chemokine receptor and that did not persist beyond 2 weeks.

Proliferation responses to HIVp24 during antiretroviral therapy do not reflect improved immune phenotype or function.

Objective: To ascertain whether lymphoproliferation (LP) responses to HIVp24 in chronically infected patients treated with antiretroviral therapy (ART) predict an improved cytolytic T-cell phenotype or better in vivo immune function as measured by immunization responses.

Methods: HIV-infected patients who started ART during chronic infection and who achieved viral suppression (HIV-RNA < 400 copies/ml for > 12 months) were grouped by the presence of strong [stimulation index (SI) > 10; n = 21] or absent (SI < 3; n = 18) LP to HIV-core antigen. The two groups were compared for functional immune responses to vaccination with diphtheria-toxoid, tetanus-toxoid and keyhole-limpet-hemocyanin, frequency of circulating naive and memory CD4+ and CD8+ T lymphocytes, maturation phenotype and expression of cytolytic molecules on total and HIV-specific CD8+ T cells, and frequency of memory CD4+ T cells with intracellular HIV-mRNA.

Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication.

Objective: Mechanisms underlying mucosal transmission of HIV-1 are incompletely understood. We describe the anti-HIV-1 activity of human beta-defensins (hBD), small cationic molecules that provide protection at mucosal surfaces.

Methods And Results: HIV-1 induced expression of hBD-2 and -3 mRNA (but not that of hBD-1) 4- to 78-fold, respectively, above baseline in normal human oral epithelial cells.

Nadir CD4+ T-cell count and numbers of CD28+ CD4+ T-cells predict functional responses to immunizations in chronic HIV-1 infection.

Objective: To ascertain whether delaying the initiation of highly active antiretroviral therapy (HAART) compromises functional immune reconstitution in HIV-1 infection in persons who regain 'normal' CD4 T-cell counts after suppressive antiretroviral therapies.

Design: Prospective open-label study carried out at two University-affiliated HIV-outpatient clinics in the USA.

Subjects And Methods: Response to immunization was used as a model for in vivo functional immune competence in 29 HIV-1 infected patients with CD4 T-cell counts > 450 x 106 cells/l and HIV-RNA < 400 copies/ml for > 12 months after HAART and nine HIV-1 seronegative controls.

Impact of suppression of viral replication by highly active antiretroviral therapy on immune function and phenotype in chronic HIV-1 infection.

We compared immune phenotypes, lymphocyte proliferation (LP), and delayed type hypersensitivity (DTH) responses in 28 male antiretroviral treatment-naive and experienced HIV-1-infected patients, matched pair-wise according to age and CD4+ T-lymphocyte count. Median CD4+ T-lymphocyte counts were 441 cells/microL and 483 cells/microL and median CD4+ T-lymphocyte nadirs were 435 cells/microL and 150 cells/microL in both groups, respectively. Absolute numbers of circulating T-lymphocyte subpopulations and proportions of naive and memory T-lymphocytes were comparable in the two groups.

CD4+ T-lymphocyte nadir and the effect of highly active antiretroviral therapy on phenotypic and functional immune restoration in HIV-1 infection.

To evaluate the effects of the timing of highly active antiretroviral therapy (HAART) on immune reconstitution, we compared lymphocyte subpopulations and lymphocyte proliferation (LP) in response to Candida albicans, cytomegalovirus, HIV p24, Mycobacterium avium complex, pokeweed mitogen, streptokinase, and tetanus toxoid in 43 patients with pretherapy advanced, moderately advanced, and early chronic HIV-1 infection. All patients had recent CD4+ T-cell counts >450/microl and HIV RNA <400 copies/ml for >12 months. CD4+ nadirs were positively correlated with recent numbers of CD4+ T-cells (P < 0.