Phase I safety and immunogenicity evaluation of MVA-CMDR, a multigenic, recombinant modified vaccinia Ankara-HIV-1 vaccine candidate.

Background: We conducted a Phase I randomized, dose-escalation, route-comparison trial of MVA-CMDR, a candidate HIV-1 vaccine based on a recombinant modified vaccinia Ankara viral vector expressing HIV-1 genes env/gag/pol. The HIV sequences were derived from circulating recombinant form CRF01_AE, which predominates in Thailand. The objective was to evaluate safety and immunogenicity of MVA-CMDR in human volunteers in the US and Thailand.

In vivo oxidation in remelted highly cross-linked retrievals.

Background: Elimination of free radicals to prevent oxidation has played a major role in the development and product differentiation of the latest generation of highly cross-linked ultra-high molecular weight polyethylene bearing materials. In the current study, we (1) examined oxidation in a series of retrieved remelted highly cross-linked ultra-high molecular weight polyethylene bearings from a number of device manufacturers and (2) compared the retrieval results with findings for shelf-stored control specimens. The hypothesis was that radiation-cross-linked remelted ultra-high molecular weight polyethylene would maintain oxidative stability in vivo comparable with the stability during shelf storage and in published laboratory aging tests.

Antiretroviral therapies in women after single-dose nevirapine exposure.

Background: Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus.

Methods: In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death.

Class I HLA-A*7401 is associated with protection from HIV-1 acquisition and disease progression in Mbeya, Tanzania.

Here we explore associations between HLA variation and human immunodeficiency virus type 1 (HIV-1) acquisition and disease progression in a community cohort in Mbeya, Tanzania, a region that, despite harboring high rates of HIV-1 infection, remains understudied. African-specific allele HLA-A*74:01 was associated with decreased risk of infection (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.

Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial.

Background: Women account for an increasing proportion of patients with HIV-1 but remain underrepresented in antiretroviral clinical trials.

Objective: To evaluate sex-based differences in efficacy and adverse events in treatment-experienced, HIV-positive women and men receiving darunavir-ritonavir therapy over 48 weeks.

Design: Multicenter, open-label, phase 3b study designed to enroll a high proportion of women, with sample size determined on the basis of a noninferiority design with a maximum allowable difference of 15% in virologic response favoring men.

Evaluating the suitability of highly cross-linked and remelted materials for use in posterior stabilized knees.

Posterior stabilized (PS) knee designs are a popular choice for cruciate sacrificing knee arthroplasty procedures. The introduction of PS inserts fabricated from highly cross-linked and remelted Ultra High Molecular Weight Polyethylene (UHMWPE) has recently generated concern as these materials have been shown to possess reduced mechanical properties. This study investigated whether highly cross-linked and remelted UHMWPE material (referred to as XRP) can be expected to perform similarly to historical gamma-air polyethylene, which has suffered few reported incidences of tibial post failure.

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.

Associations of antiretroviral drug use and HIV-specific risk factors with carotid intima-media thickness.

Background: Previous research has demonstrated an increase in carotid intima-media thickness (cIMT) in HIV-infected individuals compared to controls. However, the reason for this increased level of subclinical vascular disease is unknown.

Objective: To identify HIV-related risk factors for increased cIMT.

Women experience higher rates of adverse events during hepatitis C virus therapy in HIV infection: a meta-analysis.

Background: In HIV/ hepatitis C virus (HCV) coinfection, adverse events (AEs) during HCV therapy account for 12%-39% of treatment discontinuations. It is unknown whether sex influences complications.

Methods: Meta-analysis to study the effect of sex and other predictors of AEs in 3 randomized trials, ACTG 5071, APRICOT, and ANRSHCO2-RIBAVIC of Interferon (IFN) and Pegylated IFN (PEG), both with and without Ribavirin, in HIV/HCV coinfection.

Percutaneous intervention of left main coronary artery compression by pulmonary artery aneurysm.

Background: Extrinsic compression of the left main coronary artery (LMCA) by a pulmonary artery aneurysm (PAA) has become increasingly recognized as an etiology of angina in patients with pulmonary arterial hypertension (PAH). The purpose of this study was to assess the feasibility and efficacy of LMCA stenting in the treatment LMCA stenosis because of PAA.

Methods: Retrospective analysis of data on patients with PAH who presented with angina and underwent percutaneous intervention of their LMCA compression because of PAA was performed.

Sense and significance: a mixed methods examination of meaning making after the loss of one's child.

The purpose of this mixed methods study was to identify specific themes of meaning making (sense making and benefit finding) among bereaved parents, as well as to examine associations of these themes to the severity of grief symptomatology. A sample of 156 bereaved parents responded in writing to open-ended questions about sense making and benefit finding. We assessed normative grief symptoms with the Core Bereavement Items (Burnett, Middleton, Raphael, & Martinek, 1997) and maladaptive grief symptoms with the Inventory of Complicated Grief (Prigerson et al.

Complications of HIV disease and antiretroviral treatment.

There is growing interest in the pathogenesis, treatment, and prevention of long-term complications of HIV disease and its therapies. Specifically, studies focused on cardiovascular, renal, bone, and fat abnormalities were prominent at the 17th Conference on Retroviruses and Opportunistic Infections. Although enthusiasm about the effectiveness of current antiretroviral therapy remains strong, collectively, the ongoing work in the area of HIV disease and treatment complications appears to reflect concerns that these clinical problems will continue to remain important and possibly increase over time in the current therapeutic era.

High-throughput high-resolution class I HLA genotyping in East Africa.

HLA, the most genetically diverse loci in the human genome, play a crucial role in host-pathogen interaction by mediating innate and adaptive cellular immune responses. A vast number of infectious diseases affect East Africa, including HIV/AIDS, malaria, and tuberculosis, but the HLA genetic diversity in this region remains incompletely described. This is a major obstacle for the design and evaluation of preventive vaccines.

Effects of highly active antiretroviral therapy duration and regimen on risk for mother-to-child transmission of HIV in Johannesburg, South Africa.

Background: Limited information exists about effects of different highly active antiretroviral therapy (HAART) regimens and duration of regimens on mother-to-child transmission (MTCT) of HIV among women in Africa who start treatment for advanced immunosuppression.

Methods: Between January 2004 to August 2008, 1142 women were followed at antenatal antiretroviral clinics in Johannesburg. Predictors of MTCT (positive infant HIV DNA polymerase chain reaction at 4-6 weeks) were assessed with multivariate logistic regression.

Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Antiretroviral Therapy: ACTG Study A5152s Stein: Lipoprotein Changes on Antiretroviral Therapy.

BACKGROUND: Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized. OBJECTIVE: To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins.

Performance of serum-supplemented and serum-free media in IFNgamma Elispot Assays for human T cells.

The choice of serum for supplementation of media for T cell assays and in particular, Elispot has been a major challenge for assay performance, standardization, optimization, and reproducibility. The Assay Working Group of the Cancer Vaccine Consortium (CVC-CRI) has recently identified the choice of serum to be the leading cause for variability and suboptimal performance in large international Elispot proficiency panels. Therefore, a serum task force was initiated to compare the performance of commercially available serum-free media to laboratories' own medium/serum combinations.

Update on cardiovascular complications in HIV infection.

HIV-infected patients are at increased risk of cardiovascular disease (CVD), reflecting interaction of risk associated with host, virus, and antiretroviral therapy factors. Although traditional risk factors appear to increase risk to a similar degree in HIV-infected and HIV-uninfected persons, some risk factors (eg, smoking) may be more common in HIV-infected persons. HIV infection per se may further increase CVD risk via proatherosclerotic effects on smooth muscle cells and macrophages or by increasing inflammation.

Design and evaluation of multi-gene, multi-clade HIV-1 MVA vaccines.

Recombinant modified vaccinia virus Ankara (rMVA) expressing HIV-1 genes are promising vaccine candidates. Toward the goal of conducting clinical trials with one or a cocktail of recombinant viruses, four rMVAs expressing env and gag-pol genes from primary HIV-1 isolates representing predominant subtypes from Kenya, Tanzania, Uganda, and Thailand (A, C, D, and CRF01_AE, respectively) were constructed. Efficient expression, processing, and function of Env and Gag were demonstrated.

Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV medicine Association of the Infectious Diseases Society of America.

Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2004. The guidelines are intended for use by health care providers who care for HIV-infected patients or patients who may be at risk for acquiring HIV infection.

High-throughput genotyping of KIR2DL2/L3, KIR3DL1/S1, and their HLA class I ligands using real-time PCR.

Killer immunoglobulin-like receptors (KIRs) expressed on natural killer cells are critical components of innate immunity. Interactions between KIRs and their human leukocyte antigen (HLA) ligands have been shown to influence autoimmune and infectious disease course in defined populations. However, the low throughput and high cost of current methods impede confirmation of the universality of these findings.

Elevated natural killer cell activity despite altered functional and phenotypic profile in Ugandans with HIV-1 clade A or clade D infection.

Background And Objective: Natural killer (NK) cells most likely contribute toward limiting HIV-1 replication, and investigation into their function throughout the course of infection is therefore important. We here aimed to determine the state of the NK cell compartment in Ugandans with untreated HIV-1 clade A or D infection in comparison with matched uninfected controls.

Methods And Results: The function and phenotype of NK cells were investigated using 10-color flow cytometry.

Determinants of participation in HIV clinical trials: the importance of patients' trust in their provider.

Purpose: To investigate the factors that contribute to willingness to participate in HIV clinical trials and to determine the impact of a brief intervention on willingness to participate.

Methods: 115 consecutive outpatients receiving HIV primary care participated in this prospective study. Each patient completed a questionnaire about clinical trials and met with a research assistant who discussed the purpose of clinical trials.

Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study.

Background: Cardiovascular disease (CVD) is an increasing cause of morbidity and mortality in HIV-infected patients. However, it is controversial whether HIV infection contributes to accelerated atherosclerosis independent of traditional CVD risk factors.

Methods: Cross-sectional study of HIV-infected participants and controls without pre-existing CVD from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) and the Multi-Ethnic Study of Atherosclerosis (MESA).