Impact of a patient education program on adherence to HIV medication: a randomized clinical trial.

Patients' knowledge of their HIV condition and its treatment, which has been recognized as a factor that influences adherence to antiretroviral therapy, can be improved through educational programs. This prospective, randomized, controlled trial compared an experimental group that participated in an educational program and a control group with standard care. The study evaluated the impact of an educational intervention on adherence to antiretroviral therapy, patients' knowledge, quality of life, and therapeutic response in patients treated with highly active antiretroviral therapy.

A strategy for liquid chromatography/tandem mass spectrometric assays of intracellular drugs: application to the validation of the triphosphorylated anabolite of antiretrovirals in peripheral blood mononuclear cells.

The pharmacokinetics of intracellular drugs have recently aroused new interest because monitoring a drug's behaviour near the site of action can enhance knowledge of its efficacy and toxicity. Liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) is particularly attractive for intracellular analytes. Very few papers deal precisely with special features encountered in intracellular drug assay or with how closely the assay matches the actual recommendations.

Interferon-ribavirin in association with stavudine has no impact on plasma human immunodeficiency virus (HIV) type 1 level in patients coinfected with HIV and hepatitis C virus: a CORIST-ANRS HC1 trial.

A randomized, open-label trial was performed to study virological and intracellular interactions between stavudine and ribavirin in 30 patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Patients were randomized to receive either interferon and ribavirin or no treatment for HCV infection for 3 months. Intracellular peripheral blood mononuclear cells' stavudine-triphosphate (TP) concentrations were assessed.

Liquid chromatography-tandem mass spectrometry assays for intracellular deoxyribonucleotide triphosphate competitors of nucleoside antiretrovirals.

This study was aimed to apply an LC-MS-MS method previously developed for intracellular nucleoside reverse transcriptase inhibitors-triphosphate (NRTI-TPs) to the determination of natural deoxyribonucleotides (dNTPs) in human peripheral blood mononuclear cells. The LC-MS-MS method was directly used in assay of dATP and dTTP. Interferences by ribonucleotides (rNTPs) prevented direct application to the two other analytes: dGTP and dCTP.

Impact of antiretroviral therapy and changes in virus load on human immunodeficiency virus (HIV)-specific T cell responses in primary HIV infection.

Human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T cell responses were evaluated prospectively in a large cohort of subjects with HIV primary infection via long-term follow-up examining different virological profiles related to different treatment interventions. No correlation was observed between baseline virus load and HIV-specific CD4(+) and CD8(+) T cell responses. Highly active antiretroviral therapy (HAART)-induced suppression of viremia was associated with an increase in CD4(+) T cell proliferative responses.

Significant levels of intracellular stavudine triphosphate are found in HIV-infected zidovudine-treated patients.

Design And Objective: It has been previously shown that zidovudine (ZDV) and its phosphorylated metabolites can be chemically reduced into the corresponding stavudine (d4T) forms in solution. The aim of this study was to search for intracellular d4T-triphosphate (TP) in patients receiving ZDV therapy as part of highly active antiretroviral therapy and to examine the ratio of concentrations of d4T-TP : ZDV-TP in these patients.

Methods: Seven ml of blood were sampled between 0.

Steady-state pharmacokinetics of amprenavir coadministered with ritonavir in human immunodeficiency virus type 1-infected patients.

The protease inhibitor (PI) ritonavir is used as a strong inhibitor of cytochrome P450 3A4, which boosts the activities of coadministered PIs, resulting in augmented plasma PI levels, simplification of the dosage regimen, and better efficacy against resistant viruses. The objectives of the present open-label, multiple-dose study were to determine the steady-state pharmacokinetics of amprenavir administered at 600 mg twice daily (BID) and ritonavir administered at 100 mg BID in human immunodeficiency virus type 1 (HIV-1)-infected adults treated with different antiretroviral combinations including or not including a nonnucleoside reverse transcriptase inhibitor (NNRTI). Nineteen patients completed the study.

Increase in at-risk sexual behaviour among HIV-1-infected patients followed in the French PRIMO cohort.

Objective: With the current increase in sexually transmitted infections in industrialized countries, we assessed the characteristics and plasma viral load of HIV-1-infected patients reporting sexual behaviour at risk for HIV transmission (SBR).

Design: The study population consisted of 223 patients with primary HIV-1 infection who were enrolled in the French PRIMO cohort between 1996 and 2001 and who had at least 3 months of follow-up. Patients were interviewed on condom use at each visit according to the partner (gender, steady versus casual nature, and HIV serostatus).

Persistence of replication-competent HIV in both memory and naive CD4 T cell subsets in patients on prolonged and effective HAART.

Objective: To investigate the phenotypic features of infected lymphocytes in patients on prolonged and effective highly active antiretroviral therapy (HAART).

Design: We examined highly purified subsets of memory and naive CD4 T lymphocytes for the presence of replication-competent virus.

Methods: In 11 highly selected HAART-treated patients, we isolated highly purified CD45RO CD45RA CD4 T cells using a magnetic bead-based procedure.

In patients on prolonged HAART, a significant pool of HIV infected CD4 T cells are HIV-specific.

Objectives: To examine the antigen specificities of HIV reservoir CD4 T cells in patients on prolonged and effective highly active antiretroviral therapy (HAART).

Design: Five HIV-infected patients, who were highly adherent to antiretroviral treatment, were selected on the basis of long-term undetectable plasma viral RNA on unmodified HAART. To investigate the antigen specificities of infected memory CD4 T cells, we examined the capacity of recall antigens, including HIV antigens, to induce virus production by peripheral blood mononuclear cells (PBMC).

Development of a direct assay for measuring intracellular AZT triphosphate in humans peripheral blood mononuclear cells.

Direct LC/MS/MS methods have recently been developed for measuring triphosphate anabolites of several nucleosidic reverse transcriptase inhibitor (NRTI) in peripheral blood mononuclear cells (PBMCs) from HIV-positive patients. Whereas AZT is one of the most-used NRTIs, no such method has been developed for AZT-TP, its active anabolite, mainly because of the presence of endogenous nucleotides that interfere with such an assay. In this paper, we first describe the development of two enzyme immunoassays (EIA) of AZT-TP in PBMCs: one directly measuring AZT-TP content; the other, measuring the nucleoside AZT after selective extraction of AZT-TP and dephosphorylation.

[Management of antiretroviral treatment in HIV-infected patients exhibiting virologic failure].

THE BASES OF THERAPEUTIC FAILURE: In view of its varying clinical, immunological and virological components, therapeutic failure during HIV infection is debatable. It relies on monitoring the patient during treatment, taking into account prior therapy and the initial level of CD4 and HIV viral charge, and their evolution. Immuno-virological failure can be defined as a detectable viral charge and CD4 lymphocytes lesser than 200 elements/mm3.

An explosive course of squamous cell penile cancer in an AIDS patient.

We report the case of a 37-year-old man in whom penile cancer was discovered while he was treated for AIDS 4 years after a human papillomavirus (HSV) infection. Despite initially localised disease with T1 N0 staging, he died of metastasis within 3 years. A brief review of the literature regarding HPV-related cancer in HIV-infected patients is presented and therapeutic options are discussed.

Improved method for the simultaneous determination of d4T, 3TC and ddl intracellular phosphorylated anabolites in human peripheral-blood mononuclear cells using high-performance liquid chromatography/tandem mass spectrometry.

There is still a need for direct determination (i.e. without dephosphorylation) of nucleoside reverse transcriptase inhibitor (NRTI) triphosphorylated nucleotides in the peripheral-blood mononuclear cells (PBMCs) of HIV-positive patients.

Reduced blood CD123+ (lymphoid) and CD11c+ (myeloid) dendritic cell numbers in primary HIV-1 infection.

Successful immunologic control of HIV infection is achieved only in rare individuals. Dendritic cells (DCs) are required for specific antigen presentation to naive T lymphocytes and for antiviral, type I interferon secretion. Two major blood DC populations are found: CD11c+ (myeloid) DCs, which secrete IL-12, and CD123+ (IL-3-receptor+) DCs (lymphoid), which secrete type I interferons in response to viral stimuli.

Lipodystrophy in 685 HIV-1-treated patients: influence of antiretroviral treatment and immunovirological response.

Purpose: To describe the clinical features in HIV-1-infected patients treated with protease inhibitors (PIs) or not, and to determine factors related to occurrence of lipodystrophy (LD).

Method: We performed a cross-sectional analysis of 685 treated HIV-1-infected patients that were routinely followed in 6 Paris hospital centers between January and May 1999. Demographic data, familial and personal vascular risk factors, history of antiretroviral treatment, HIV plasma viral load, CD4 cell count, and metabolic data were collected.

Direct determination of phosphorylated intracellular anabolites of stavudine (d4T) by liquid chromatography/tandem mass spectrometry.

The objective was to develop and validate a routine assay for active intracellular anabolites of stavudine (d4T), a nucleoside reverse transcriptase inhibitor in human PBMC, applicable to pharmacokinetic studies and treatment monitoring. This was achieved using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS), which theoretically allies optimum sensitivity, specificity and high sample throughput. After cellular lysis in a Tris/methanol buffer, the extract spiked with 2[H(8)]-ATP (internal standard) is directly injected into the LC/MS/MS system.

Proviral HIV-1 DNA in subjects followed since primary HIV-1 infection who suppress plasma viral load after one year of highly active antiretroviral therapy.

Objective: An assessment of the impact of one year potent antiretroviral treatment initiated during primary HIV infection on the cell-associated viral burden.

Design And Methods: Proviral HIV-1 DNA was quantified in serial peripheral blood mononuclear cell (PBMC) samples from 19 patients enrolled in the French prospective PRIMO Cohort for whom plasma HIV RNA was suppressed to undetectable levels after one year of triple therapy; that is, plasma HIV-1 RNA was maintained below 200 copies/ml. Results were compared with those observed in 19 patients with chronic HIV-1 infection presenting the same degree of virus suppression after 12 months of treatment.

Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy.

Background: The prognostic value of discordant immunologic (CD4 cell increase) and virologic (plasma HIV RNA level decrease) responses to antiretroviral treatment is not known.

Objective: To study the relation between clinical outcome of HIV-infected patients receiving highly active antiretroviral therapy (HAART) and early immunologic and virologic responses to such therapy.

Design: Prospective cohort study.