Lopinavir/ritonavir monotherapy versus current treatment continuation for maintenance therapy of HIV-1 infection: the KALESOLO trial.

Objectives: We evaluated a monotherapy maintenance regimen with lopinavir/ritonavir versus continuing current combined antiretroviral treatment (cART) in HIV patients with suppressed plasma HIV-1 RNA.

Patients And Methods: This was an open-label, non-inferiority, multicentre trial in 23 sites in France. Adults were randomized if they had no history of virological failure while receiving a protease inhibitor, maintained HIV-1 RNA <50 copies/mL for at least 6 months and did not change cART during the last 3 months.

Close association of CD8+/CD38 bright with HIV-1 replication and complex relationship with CD4+ T-cell count.

Background: Measuring lymphocyte activation provides information in addition to CD4(+) T-cell count for immune monitoring of HIV-1 infected patients. CD38 is a well-established activation marker that is generally analyzed on the whole population of CD8(+) T-cells. Focusing specifically on CD38 high expression (CD8(+)/CD38(bright)) may be an interesting surrogate gating strategy because CD38(bright) characterizes principally activated memory cells.

Long-term persistence of memory B cells specific for hepatitis B surface antigen in HIV-1-infected patients.

To investigate the maintenance of long-term memory B cells specific for hepatitis B surface antigen (HBsAg), purified blood B cells were polyclonally stimulated and cells secreting antibodies directed to HBsAg (HBs-SC) enumerated by ELISpot. HBs-SC were found in 18/20 HIV-1-infected patients with either natural or vaccinal immunity to hepatitis B virus, including six subjects with serum anti-hepatitis B surface antibody levels less than 10 mIU/ml. A lower number of HBs-SC was found in HBsAg-vaccinated patients compared with vaccinated controls.

Suppression of microRNA-silencing pathway by HIV-1 during virus replication.

MicroRNAs (miRNAs) are single-stranded noncoding RNAs of 19 to 25 nucleotides that function as gene regulators and as a host cell defense against both RNA and DNA viruses. We provide evidence for a physiological role of the miRNA-silencing machinery in controlling HIV-1 replication. Type III RNAses Dicer and Drosha, responsible for miRNA processing, inhibited virus replication both in peripheral blood mononuclear cells from HIV-1-infected donors and in latently infected cells.

Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency.

HIV-1 gene expression is the major determinant regulating the rate of virus replication and, consequently, AIDS progression. Following primary infection, most infected cells produce virus. However, a small population becomes latently infected and constitutes the viral reservoir.

Is tenofovir involved in hypophosphatemia and decrease of tubular phosphate reabsorption in HIV-positive adults?

Objectives: Tubulopathy with hypophosphatemia have been observed in HIV-positive patients receiving a tenofovir-containing regimen. However, the real incidence and prevalence of hypophosphatemia and their relation to tubular reabsorption disorders in tenofovir-treated patients remain uncertain. The aim of our study was to explore the effect of tenofovir on phosphatemia and on tubular phosphate reabsorption.

CXCR4 overexpression during the course of HIV-1 infection correlates with the emergence of X4 strains.

The factors that determine the emergence of X4 isolates in some HIV-1-infected subjects are unknown. As the level of expression of CXCR4 could favor an R5 to X4 switch, quantitative flow cytometry was used to measure CXCR4 density on CD4 T cells in 200 HIV-1-positive adults, and this was compared with CD4 counts, interleukin-7 (IL-7), and RANTES (regulated on activation, normal T expressed and secreted) plasma levels and the R5/X4 virus phenotype. CD4 T-cell surface CXCR4 densities were increased in infected subjects and inversely correlated with CD4 T-cell count (r=-0.

T-Cell surface CCR5 density is not correlated with hepatitis severity in hepatitis C virus/HIV-coinfected individuals: implications for the therapeutic use of CCR5 antagonists.

CCR5 antagonists represent promising anti-HIV agents. Yet, if the CCR5 chemokine receptor plays a positive role in hepatitis C virus (HCV) infection, CCR5 antagonists might be contraindicated in HCV/HIV-coinfected subjects. Therefore, we tested the hypothesis that the level of T-cell surface CCR5 expression, which might determine the intensity of HCV-specific T-cell recruitment into the liver, and thereby the efficiency of the anti-HCV response, could determine HCV disease evolution.

Human immunodeficiency virus type 1 (HIV-1) antigen secretion by latently infected resting CD4+ T lymphocytes from HIV-1-infected individuals.

In resting CD4(+) T lymphocytes harboring human immunodeficiency virus type 1 (HIV-1), replication-competent virus persists in patients responding to highly active antiretroviral therapy (HAART). This small latent reservoir represents between 10(3) and 10(7) cells per patient. However, the efficiency of HIV-1 DNA-positive resting CD4(+) T cells in converting to HIV-1-antigen-secreting cells (HIV-1-Ag-SCs) after in vitro CD4(+)-T-cell polyclonal stimulation has not been satisfactorily evaluated.

Fenofibrate improves the atherogenic lipid profile and enhances LDL resistance to oxidation in HIV-positive adults.

Background: Low HDL-cholesterol, hypertriglyceridemia (HTG) and occurrence of small dense LDL could be involved in increased cardiovascular risk in HIV-infected patients. This study evaluates the effects of fenofibrate and/or Vitamin E on lipoprotein profile.

Design: Thirty-six HIV-positive adults with fasting triglycerides (TGs) > or =2 mmol/l and stable antiretroviral therapy (ART) were randomly assigned to receive either micronised fenofibrate (200 mg/day) or Vitamin E (500 mg/day) for a first period of 3 months and the association of both for an additional 3-month period.

Detection and enumeration of circulating HIV-1-specific memory B cells in HIV-1-infected patients.

Memory B cells are long-living cells that circulate throughout the body and differentiate into plasma cells after stimulation by antigens, cytokines, and direct cell-to-cell interaction in lymphoid tissues. For HIV-1-infected patients, we assessed whether in vitro polyclonal B cell activation that induces immunoglobulin secreting cells (SCs) also generates HIV-1-specific resting B cells to synthesize antibodies specific to HIV-1. To this end, highly purified B cells from 10 HIV-1-untreated patients were cultured with or without mouse fibroblastic cells expressing the CD40 ligand in the presence of IL-2 and IL-10.

Enumeration of latently infected CD4+ T cells from HIV-1-infected patients using an HIV-1 antigen ELISPOT assay.

Background: Latently infected resting CD4(+) T cells carrying replication-competent HIV-1 are present in naive, chronically infected individuals as well as in those who are receiving highly active antiretroviral therapy (HAART). These cells serve as a potential source of reactivation of viral replication and remain a major obstacle for the eradication of HIV-1.

Objectives: The enzyme-linked immunospot (ELISPOT) assay was adapted to the detection and the enumeration of HIV-1 antigen-secreting cells at the single cell level.

Detection of peripheral HIV-1-specific memory B cells in patients untreated or receiving highly active antiretroviral therapy.

Objectives: To examine whether polyclonal activation of circulating B cells, in a process that involves CD40-CD40 ligand and cytokine interactions, could induced HIV-1-specific memory B cells to synthesize HIV-1-specific antibodies.

Methods: B cells from 26 HIV-1-infected patients were cultured with a CD40L-transfected cell line plus interleukins 2 and 10 and tested for their secretion of HIV-1- and Toxoplasma gondii-specific antibodies.

Results: In vitro activated B lymphocytes from HIV-1-infected patients secreted anti-HIV-1-specific antibodies.

Reasons for early abacavir discontinuation in HIV-infected patients.

Objective: To determine incidence of and reasons for discontinuation of abacavir within the first 6 months of therapy.

Methods: Retrospective study performed in the cohort of HIV-infected adults who started abacavir in a medical unit between 1997 and December 2000. All adverse drug reactions (ADRs) (especially hypersensitivity) observed in this cohort were reported.

Decrease in LDL size in HIV-positive adults before and after lopinavir/ritonavir-containing regimen: an index of atherogenicity?

Background: Hypertriglyceridemia (HTG) is frequently observed during highly active antiretroviral therapy (HAART) including protease inhibitor. Apolipoprotein (apo) CIII could be involved in this HTG by inhibition of triglyceride (TG) hydrolysis, which leads to the occurrence of small dense low density lipoprotein (sdLDL), a recognized cardiovascular risk factor.

Objective: To characterize the influence of lopinavir/ritonavir-containing regimen on lipoprotein profile.

Perforin expression in T cells and virological response to PEG-interferon alpha2b in HIV-1 infection.

Objective And Design: Interferon alpha (IFNalpha), which is known to directly inhibit the HIV-1 replicative cycle and to increase the activity of cytotoxic T lymphocytes (CTL), is being tested as an anti-HIV agent. As CTL play a major role in immune defence against HIV, we wanted to further characterize CTL activity and the effect of IFNalpha on it.

Methods: We followed by flow cytometry the intracellular expression of the key mediator of cytotoxicity, perforin, in peripheral blood T cells of patients treated with IFNalpha.

Interferon-alpha restores HIV-induced alteration of natural killer cell perforin expression in vivo.

Objective: The percentage and the activity of natural killer (NK) cells are known to be decreased in HIV-infected patients. However, the mechanisms responsible for this NK deficiency are poorly understood. Because of the role of NK cells in the host defence against microbial infections, this defect contributes to the virus-induced immune deficiency.

Dynamics of spontaneous HIV-1 specific and non-specific B-cell responses in patients receiving antiretroviral therapy.

Objectives: As spontaneous anti-HIV-1 antibody and IgG secretion by peripheral blood mononuclear cells (PBMC) reflect immune system activation by HIV-1 antigens, we evaluated the impact of antiretroviral therapies on HIV-1 specific and non-specific B cell responses.

Methods: Anti-HIV-1 antibody and non-specific IgG were measured by ELISA in supernatants of PBMC cultured during 7 day from 30 patients initiating an antiretroviral therapy at baseline, 8, 16, 24, 36 and 48 weeks.

Results: An early and sustained fall in plasma viral load to below the detection limit (20 copies/ml) was observed in 17 sustained responder patients (SR), whereas HIV-1 RNA remained detectable in 13 others incomplete responders.