Macro CK2 accumulation in tenofovir-treated HIV patients is facilitated by CK oligomer stabilization but is not predictive for pathology.

Background: Ubiquitous mitochondrial creatine kinase (uMtCK) accumulates as macroenzyme creatine kinase type 2 (macro CK2) in the serum of HIV-infected patients under a tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimen. The genesis and clinical significance of this finding is unclear.

Methods: A prospective observational 5-year follow-up study was performed on those patients in which macro CK2 appearance was initially described ('TDF switch study' cohort).

Longitudinal changes in HIV-1-specific T-cell quality associated with viral load dynamic.

Background: Several correlates of HIV control have been described; however their predictive values remain unclear, since most studies have been performed in cross-sectional settings.

Objectives: We evaluated the cause and consequence relationship between quality of HIV-specific T-cell response and viral load dynamic in a temporal perspective.

Study Design: HIV-1-specific T-cell responses were monitored over 7 years in a patient that following treatment interruption maintained a stable/low viral set point for 3.

Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma are associated with nonprogressive HIV-1 infection.

Background: Long-term survival of HIV-1 infected individuals is usually achieved by continuous administration of combination antiretroviral therapy (ART). An exception to this scenario is represented by HIV-1 infected nonprogressors (NP) which maintain relatively high circulating CD4+ T cells without clinical symptoms for several years in the absence of ART. Several lines of evidence indicate an important role of the T-cell response in the modulation of HIV-1 infection during the acute and chronic phase of the disease.

Impact of changes in antigen level on CD38/PD-1 co-expression on HIV-specific CD8 T cells in chronic, untreated HIV-1 infection.

Excessive immune activation is a hallmark of chronic uncontrolled HIV infection. During the past years, growing evidence suggests that immune inhibitory signals also play an important role in progressive disease. However, the relationship between positive and negative immune signals on HIV-specific CD8 T cells has not been studied in detail so far in chronic HIV-1 infection.

The intracellular detection of MIP-1beta enhances the capacity to detect IFN-gamma mediated HIV-1-specific CD8 T-cell responses in a flow cytometric setting providing a sensitive alternative to the ELISPOT.

Background: T-cell mediated immunity likely plays an important role in controlling HIV-1 infection and progression to AIDS. Several candidate vaccines against HIV-1 aim at stimulating cellular immune responses, either alone or together with the induction of neutralizing antibodies, and assays able to measure CD8 and CD4 T-cell responses need to be implemented. At present, the IFN-gamma-based ELISPOT assay is considered the gold standard and it is broadly preferred as primary assay for detection of antigen-specific T-cell responses in vaccine trials.

Therapeutic vaccination reduces HIV sequence variability.

With HIV persisting lifelong in infected persons, therapeutic vaccination is a novel alternative concept to control virus replication. Even though CD8 and CD4 cell responses to such immunizations have been demonstrated, their effects on virus replication are still unclear. In view of this fact, we studied the impact of a therapeutic vaccination with HIV nef delivered by a recombinant modified vaccinia Ankara vector on viral diversity.

Long-term effect on body composition and metabolic parameters after treatment with recombinant human growth hormone (r-hGH) in HIV-1 infected patients with lipodystrophy.

Several studies have shown reduction of visceral adipose tissue (VAT) using recombinant human growth hormone (r-hGH) in HIV-1+ patients, but whether these effects are maintained after the end of treatment is unknown. In a prospective, randomized study we previously studied the effects of r-hGH 4 mg daily vs 3 times/week over 12 weeks, followed by a 2 mg daily maintenance dose for an additional 12 weeks. T1 weighted MRI flash sequences were performed of the face, abdomen and at mid-thigh level (MTF) at baseline, week 12, week 24 and at follow-up.

Evaluation of modified vaccinia virus Ankara as an alternative vaccine against smallpox in chronically HIV type 1-infected individuals undergoing HAART.

The fear of malevolent use of variola virus by terrorists has led to the implementation of a health care worker vaccination program and to the consideration of vaccination for the general public. However, due to concerns about side effects of the classical smallpox vaccine, especially for immunocompromised individuals, a safer vaccine is urgently needed. We characterized the immunogenicity of modified vaccinia virus Ankara (MVA), one of the more promising alternative smallpox vaccines, in a cohort of 10 chronically HIV-1-infected individuals undergoing highly active antiretroviral therapy (HAART).

Macroenzyme creatine kinase (CK) type 2 in HIV-infected patients is significantly associated with TDF and consists of ubiquitous mitochondrial CK.

Objective: To evaluate the prevalence and origin of macroenzyme creatine kinase type 2 (Macro CK2) in HIV-1-infected patients on antiretroviral treatment.

Design: CK, CK-MB activity and protein weight, electrophoretic behaviour, glomerular filtration rate (GFR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), bone alkaline phosphatase (AP), beta2-microglobulin serum levels and proteinuria were analysed in 468 HIV-infected outpatients. Sera with detectable Macro CK2 were further analysed using immunoblotting.

Vaccines based on Nef and on Nef/DeltaV2 Env.

Modified vaccinia virus Ankara (MVA) is a potent vaccine vector, which proved its safety, immunogenity and efficacy in preclinical and clinical studies. The rational for the development of a vaccine against HIV based on the regulatory protein Nef delivered by MVA combined with a V2-deleted Env protein is discussed.

Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1.

We assessed the efficacy and safety of 10-d monotherapy with the orally administered CCR5 antagonist maraviroc in 63 HIV-1-positive individuals prescreened for the absence of CXCR4-using virus. Maximum reduction in viral load occurred at a median of 10-15 d, with a mean reduction of >or=1.6 log(10) copies/ml at all twice daily doses >or=100 mg.

Neutralization assay using a modified vaccinia virus Ankara vector expressing the green fluorescent protein is a high-throughput method to monitor the humoral immune response against vaccinia virus.

Vaccination against smallpox is again considered in order to face a possible bioterrorist threat, but the nature and the level of the immune response needed to protect a person from smallpox after vaccination are not totally understood. Therefore, simple, rapid, and accurate assays to evaluate the immune response to vaccinia virus need to be developed. Neutralization assays are usually considered good predictors of vaccine efficacy and more informative with regard to protection than binding assays.

Therapeutic vaccination with MVA-HIV-1 nef elicits Nef-specific T-helper cell responses in chronically HIV-1 infected individuals.

Vaccination is currently considered as an additional therapeutic approach to stimulate HIV-specific immune response in subjects that could not naturally control HIV. Ten chronically HIV infected individuals have been vaccinated with a modified vaccinia Ankara (MVA)-HIV-1(LAI)-nef vector in order to assess safety and immunogenicity. No significant adverse effects were observed during the course of vaccination indicating for the first time that the highly attenuated vaccinia-virus vector MVA is safe in HIV-1 infected individuals.