Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference

EUROPRISE is a Network of Excellence sponsored from 2007 to 2011 by the European Commission within the 6th Framework Program. The Network encompasses a wide portfolio of activities ranging from an integrated research program in the field of HIV vaccines and microbicides to training, dissemination and advocacy. The research program covers the whole pipeline of vaccine and microbicide development from discovery to early clinical trials. The Network is composed of 58 partners representing more than 65 institutions from 13 European countries; it also includes three major pharmaceutical companies (GlaxoSmithKline, Novartis and Sanofi-Pasteur) involved in HIV microbicide and vaccine research. The Network displays a dedicated and informative web page: http://www.europrise.org. Finally, a distinguishing trait of EUROPRISE is its PhD School of students from across Europe, a unique example in the world of science aimed at spreading excellence through training

Does personality play a role in continuous positive airway pressure compliance?

Key points Continuous positive airway pressure (CPAP) adherence is low among individuals with obstructive sleep apnoea. Type D personality and high scores on the depression and hypochondriasis scales on the Minnesota Multiphasic Personality Inventory (MMPI) have been identified as factors contributing to non-compliance with CPAP. Further research into personality type may assist in understanding why some people adhere to CPAP, while others fail. Obstructive sleep apnoea (OSA) is a condition characterised by repetitive, intermittent partial or complete collapse/obstruction of the upper airway during sleep. Continuous positive airway pressure (CPAP) is highly efficacious in treating OSA but its effectiveness is limited due to suboptimal acceptance and adherence rates, with as many as 50% of OSA patients discontinuing CPAP treatment within the first year. Until recently, research has focused on examining mechanistic and demographic factors that could explain nonadherence (e.g. age, sex, race and education level) with limited applicability in a prospective or clinical manner. More recent research has focused on personality factors or types of patients with OSA who comply and do not comply with CPAP adherence in an attempt to enhance the accuracy of predicting treatment compliance. Type D personality has been found to be prevalent in one third of patients with OSA. The presence of Type D personality increases noncompliance and poor treatment outcomes due to negative affectivity, social inhibition, unhealthy lifestyle, and a reluctance to consult and/or follow medical advice. Conversely, individuals who are more likely to adhere to CPAP treatment tend to have a high internal locus of control and high self-efficacy, self-refer for treatment, and have active coping skills. By assessing personality and coping skills, the clinician may gain insight into the likelihood of a patient’s adherence to treatment. If the patient displays potential risk factors for CPAP noncompliance, the clinician can offer the patient education, refer them to a support group, engage in behavioural/motivational therapy and undertake regular follow-up visits or phone calls incorporating troubleshooting to increase CPAP adherence, especially in individuals with Type D personality

Dual Testing Algorithm of BED-CEIA and AxSYM Avidity Index Assays Performs Best in Identifying Recent HIV Infection in a Sample of Rwandan Sex Workers

To assess the performance of BED-CEIA (BED) and AxSYM Avidity Index (Ax-AI) assays in estimating HIV incidence among female sex workers (FSW) in Kigali, Rwanda. Eight hundred FSW of unknown HIV status were HIV tested; HIV-positive women had BED and Ax-AI testing at baseline and ≥12 months later to estimate assay false-recent rates (FRR). STARHS-based HIV incidence was estimated using the McWalter/Welte formula, and adjusted with locally derived FRR and CD4 results. HIV incidence and local assay window periods were estimated from a prospective cohort of FSW. At baseline, 190 HIV-positive women were BED and Ax-AI tested; 23 were classified as recent infection (RI). Assay FRR with 95% confidence intervals were: 3.6% (1.2-8.1) (BED); 10.6% (6.1-17.0) (Ax-AI); and 2.1% (0.4-6.1) (BED/Ax-AI combined). After FRR-adjustment, incidence estimates by BED, Ax-AI, and BED/Ax-AI were: 5.5/100 person-years (95% CI 2.2-8.7); 7.7 (3.2-12.3); and 4.4 (1.4-7.3). After CD4-adjustment, BED, Ax-AI, and BED/Ax-AI incidence estimates were: 5.6 (2.6-8.6); 9.7 (5.0-14.4); and 4.7 (2.0-7.5). HIV incidence rates in the first and second 6 months of the cohort were 4.6 (1.6-7.7) and 2.2 (0.1-4.4). Adjusted incidence estimates by BED/Ax-AI combined were similar to incidence in the first 6 months of the cohort. Furthermore, false-recent rate on the combined BED/Ax-AI algorithm was low and substantially lower than for either assay alone. Improved assay specificity with time since seroconversion suggests that specificity would be higher in population-based testing where more individuals have long-term infectio

Dynamics of Envelope Evolution in Clade C SHIV-Infected Pig-Tailed Macaques during Disease Progression Analyzed by Ultra-Deep Pyrosequencing

Understanding the evolution of the human immunodeficiency virus type 1 (HIV-1) envelope during disease progression can provide tremendous insights for vaccine development, and simian-human immunodeficiency virus (SHIV) infection of non-human primate provides an ideal platform for such studies. A newly developed clade C SHIV, SHIV-1157ipd3N4, which was able to infect rhesus macaques, closely resembled primary HIV-1 in transmission and pathogenesis, was used to infect several pig-tailed macaques. One of the infected animals subsequently progressed to AIDS, whereas one remained a non-progressor. The viral envelope evolution in the infected animals during disease progression was analyzed by a bioinformatics approach using ultra-deep pyrosequencing. Our results showed substantial envelope variations emerging in the progressor animal after the onset of AIDS. These envelope variations impacted the length of the variable loops and charges of different envelope regions. Additionally, multiple mutations were located at the CD4 and CCR5 binding sites, potentially affecting receptor binding affinity, viral fitness and they might be selected at late stages of disease. More importantly, these envelope mutations are not random since they had repeatedly been observed in a rhesus macaque and a human infant infected by either SHIV or HIV-1, respectively, carrying the parental envelope of the infectious molecular clone SHIV-1157ipd3N4. Moreover, similar mutations were also observed from other studies on different clades of envelopes regardless of the host species. These recurring mutations in different envelopes suggest that there may be a common evolutionary pattern and selection pathway for the HIV-1 envelope during disease progression

Identification of Peptide Mimotopes of Trypanosoma brucei gambiense Variant Surface Glycoproteins

The control of human African trypanosomiasis or sleeping sickness, a deadly disease in sub-Saharan Africa, mainly depends on a correct diagnosis and treatment. The aim of our study was to identify mimotopic peptides (mimotopes) that may replace the native proteins in antibody detection tests for sleeping sickness and hereby improve the diagnostic sensitivity and specificity. We selected peptide expressing phages from the PhD.-12 and PhD.-C7C phage display libraries with mouse monoclonal antibodies specific to variant surface glycoprotein (VSG) LiTat 1.3 or LiTat 1.5 of Trypanosoma brucei gambiense. The peptide coding genes of the selected phages were sequenced and the corresponding peptides were synthesised. Several of the synthetic peptides were confirmed as mimotopes for VSG LiTat 1.3 or LiTat 1.5 since they were able to inhibit the binding of their homologous monoclonal to the corresponding VSG. These peptides were biotinylated and their diagnostic potential was assessed with human sera. We successfully demonstrated that human sleeping sickness sera recognise some of the mimotopes of VSG LiTat 1.3 and LiTat 1.5, indicating the diagnostic potential of such peptides

Molecular Evolution of HIV-1 CRF01_AE Env in Thai Patients

BACKGROUND: The envelope glycoproteins (Env), gp120 and gp41, are the most variable proteins of human immunodeficiency virus type 1 (HIV-1), and are the major targets of humoral immune responses against HIV-1. A circulating recombinant form of HIV-1, CRF01_AE, is prevalent throughout Southeast Asia; however, only limited information regarding the immunological characteristics of CRF01_AE Env is currently available. In this study, we attempted to examine the evolutionary pattern of CRF01_AE Env under the selection pressure of host immune responses. METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood samples were collected periodically over 3 years from 15 HIV-1-infected individuals residing in northern Thailand, and amplified env genes from the samples were subjected to computational analysis. The V5 region of gp120 showed highest variability in several samples over 3 years, whereas the V1/V2 and/or V4 regions of gp120 also showed high variability in many samples. In addition, the N-terminal part of the C3 region of gp120 showed highest amino acid diversity among the conserved regions of gp120. Chronological changes in the numbers of amino acid residues in gp120 variable regions and potential N-linked glycosylation (PNLG) sites are involved in increasing the variability of Env gp120. Furthermore, the C3 region contained several amino acid residues potentially under positive selection, and APOBEC3 family protein-mediated G to A mutations were frequently detected in such residues. CONCLUSIONS/SIGNIFICANCE: Several factors, including amino acid substitutions particularly in gp120 C3 and V5 regions as well as changes in the number of PNLG sites and in the length of gp120 variable regions, were revealed to be involved in the molecular evolution of CRF01_AE Env. In addition, a similar tendency was observed between CRF01_AE and subtype C Env with regard to the amino acid variation of gp120 V3 and C3 regions. These results may provide important information for understanding the immunological characteristics of CRF01_AE Env

Durability of treatment effects of the Sleep Position Trainer versus oral appliance therapy in positional OSA: 12-month follow-up of a randomized controlled trial

The Sleep Position Trainer (SPT) is a new option for treating patients with positional obstructive sleep apnea (POSA). This study investigated long-term efficacy, adherence, and quality of life during use of the SPT device compared with oral appliance therapy (OAT) in patients with POSA. This prospective, multicenter trial randomized patients with mild to moderate POSA (apnea-hypopnea index [AHI] 5-30/h) to SPT or OAT. Polysomnography was performed at baseline and after 3 and 12 months' follow-up. The primary endpoint was OSA severity; adherence, quality of life, and adverse events were also assessed. Ninety-nine patients were randomized and 58 completed the study (29 in each group). Median AHI in the SPT group decreased from 13.2/h at baseline to 7.1/h after 12 months (P < 0.001); corresponding values in the OAT group were 13.4/h and 5.0/h (P < 0.001), with no significant between-group difference (P = 1.000). Improvements throughout the study were maintained at 12 months. Long-term median adherence was also similar in the two treatment groups; the proportion of patients who used their device for ≥ 4 h for 5 days in a week was 100% in the SPT group and 97.0% in the OAT group (P = 0.598). The efficacy of SPT therapy was maintained over 12 months and was comparable to that of OAT in patients with mild to moderate POSA. Adherence was relatively high, and similar in the two groups. www.clinicaltrials.gov (NCT02045576