Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a phase 2 randomised, double-blind, placebo-controlled trial.

Background: Present combination antiretroviral therapy (cART) alone does not cure HIV infection and requires lifelong drug treatment. The potential role of HIV therapeutic vaccines as part of an HIV cure is under consideration. Our aim was to assess the efficacy, safety, and immunogenicity of Vacc-4x, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24(Gag), in adults infected with HIV-1.

Boosters of a therapeutic HIV-1 vaccine induce divergent T cell responses related to regulatory mechanisms.

Therapeutic human immunodeficiency virus (HIV) vaccines aim to reduce disease progression by inducing HIV-specific T cells. Vacc-4x are peptides derived from conserved domains within HIV-1 p24 Gag. Previously, Vacc-4x induced T cell responses in 90% of patients which were associated with reduced viral loads.

Delayed-type hypersensitivity responses to HIV Gag p24 relate to clinical outcome after peptide-based therapeutic immunization for chronic HIV infection.

Therapeutic immunization in chronic HIV infection aims to induce durable, HIV-specific immune responses capable of controlling disease progression, but immunological correlates of clinical efficacy are poorly defined. We have previously immunized 38 patients with a mixture of four short Gag p24-like conserved peptides (Vacc-4x) targeting skin dendritic cells. Antiretroviral treatment (ART) was initially stopped after completed immunizations and resumed post-protocol during regular clinical follow-up according to current guidelines.

Intradermal vaccination of HIV-infected patients with short HIV Gag p24-like peptides induces CD4 + and CD8 + T cell responses lasting more than seven years.

Background: Vacc-4x contains 4 HIV p24-like short peptides. In a previous phase II trial this immunized 90% of 38 patients on antiretroviral treatment (ART) after intradermal delivery in conjunction with local granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjuvant. In this study, 22 responders were retested for cellular memory at a median 7.

Long-term HIV-specific responses and delayed resumption of antiretroviral therapy after peptide immunization targeting dendritic cells.

Long-term HIV-specific immune responses and clinical outcomes were evaluated in HIV-infected patients previously immunized with p24-like peptides (Vacc-4x) targeting dendritic cells (DC). Vacc-4x-induced cellular immune responses were unchanged 1.5 years after completing immunization, and 62% were still off combined antiretroviral treatment (CART).

Multiple antigen concentrations in delayed-type hypersensitivity (DTH) and response diversity during and after immunization with a peptide-based HIV-1 immunotherapy candidate (Vacc-4x).

Delayed-type hypersensitivity (DTH) testing represents a simple in vivo method for monitoring cellular immune responses. In a phase II clinical trial on HIV-infected patients (n = 38) of the peptide-based HIV-1 immunotherapy candidate Vacc-4x, we monitored DTH responses to three antigen concentrations of Vacc-4x. We have shown that DTH can be used quantitatively to measure immune reactions to Vacc-4x and its individual peptide components.

Reduced viral burden amongst high responder patients following HIV-1 p24 peptide-based therapeutic immunization.

We have previously shown that HIV p24-like peptides (Vacc-4x) via activation of skin dendritic cells induced immune responses in 90% of HIV patients on highly active antiretroviral treatment (HAART). These patients (n=38) were here subjected to a final 14-week interruption of HAART. Patients with the highest delayed type hypersensitivity (DTH) responses to Vacc-4x-peptides before treatment interruption tended to achieve lower actual HIV RNA levels at the end of the study compared to Vacc-4x DTH low-responders (p=0.

Divergent in vitro and in vivo correlates of HIV-specific T-cell responses during onset of HIV viraemia.

Background: Cellular immune responses to HIV-1 have been examined mainly in peripheral blood mononuclear cells (PBMC). During onset of HIV replication and antigenaemia after discontinuation of highly active antiretroviral therapy (HAART), PBMC may theoretically contain HIV-specific T cells that are qualitatively and quantitatively different from specific T cells dominating in the tissues. PBMC responses throughout HIV immunotherapy trials may therefore be skewed during recurrent viraemia.

HLA- and dose-dependent immunogenicity of a peptide-based HIV-1 immunotherapy candidate (Vacc-4x).

Objective: The Vacc-4x immunotherapy candidate is composed of four modified peptides corresponding to conserved domains of the HIV-1 protein p24 that preferentially include HLA-A2 restricted elements. Dose-dependent safety and immunogenicity of Vacc-4x and the significance of a HLA-A2 haplotype were examined.

Design: Non-AIDS, HIV-1 infected healthy patients (n = 40) stable on HAART with CD4 counts > 300 x 10 cells/l were randomized to receive either low-dose or high-dose Vacc-4x over 26 weeks in an open, prospective phase II clinical trial.

Phase I trial of a therapeutic HIV type 1 vaccine, Vacc-4x, in HIV type 1-infected individuals with or without antiretroviral therapy.

Highly active antiretroviral therapy (HAART) can effectively suppress HIV-1 replication but, as soon as the drugs are withdrawn, there is a rapid rebound of replicating virus. Severe metabolic toxicities and therapy failures due to the appearance of resistant virus are becoming an increasing problem that precludes long-term continuous medication. Therapeutic immunizations represent a feasible and attractive means of supplementing or, alternatively, replacing current therapies, thereby reducing the potential for emergence of drug-resistant HIV-1 strains.

Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma.

K-RAS mutations are frequently found in adenocarcinomas of the pancreas, and induction of immunity against mutant ras can therefore be of possible clinical benefit in patients with pancreatic cancer. We present data from a clinical phase I/II trial involving patients with adenocarcinoma of the pancreas vaccinated by i.d.

Improvement of serum lipids and blood pressure during intervention with n-3 fatty acids was not associated with changes in insulin levels in subjects with combined hyperlipidaemia.

Objectives: To investigate the effect of an omega-3 fatty acid concentrate K85 on serum lipids, lipoproteins, insulin metabolism and blood pressure in subjects with combined hyperlipidaemia.

Design: After a run-in dietary period of 10 weeks, subjects were randomly allocated to receive either encapsulated K85 (n = 28) or corn oil (n = 29). The intervention was double-blind.

Superparamagnetic particles as gastrointestinal contrast agent in magnetic resonance imaging of lower abdomen.

Negative gastrointestinal contrast enhancement can be achieved by oral administration of superparamagnetic particles. Their feasibility for the MR imaging of the female pelvis and lower abdomen was evaluated in studies on 32 follow-up patients with treated gynaecologic cancer. All the applied doses (0.

An estimation of the prevalence of diabetes mellitus in Norway. A prescription registration study.

A prevalence of 0.9% for drug-treated diabetes mellitus was calculated (male 0.8; female 1.

Therapeutic traditions in Northern Ireland, Norway and Sweden: II. Hypertension. WHO Drug Utilization Research Group (DURG).

A questionnaire survey based on hypertension case histories was performed among a representative sample of 400 GP's and hospital doctors in Northern Ireland, Norway and Sweden, countries having markedly different utilization of antihypertensive drugs. We found a greater propensity to start antihypertensive drug treatment in Northern Ireland than in Norway and Sweden. This was true both in mild diastolic and isolated systolic hypertension.

Therapeutic traditions in Northern Ireland, Norway and Sweden: I. Diabetes. WHO Drug Utilization Research Group (DURG).

A questionnaire survey was carried out to explore differences in the approach to treatment of patients with Type II diabetes between physicians in Northern Ireland, Norway and Sweden, and to discover to what extent it could account for the three-fold difference in drug use between the countries. A representative sample of 400 physicians in each country was asked to give their opinions on the choice of therapy for three model cases designed to cover the spectrum of treatment - from diet alone to insulin. Significantly more Swedish (65%) than Northern Irish (51%) and Norwegian (52%) doctors suggested diet alone for uncomplicated diabetes recently discovered in a middle aged, overweight man.

Validation of observed differences in the utilization of antihypertensive and antidiabetic drugs in Northern Ireland, Norway and Sweden.

The amount of antihypertensive and antidiabetic drugs based of defined daily doses per 1000 inhabitants per day varies two to three fold between Northern Ireland, Norway, and Sweden. We explored whether variations based on the universally applied defined daily doses might be accounted for by national differences in the actual average prescribed daily doses. Use of prescribed daily doses for antihypertensive drugs resulted in Northern Irish and Norwegian consumption figures which were respectively 40 and 21% lower than the Swedish one, compared to 38 and 25% when defined daily doses were used.