HIV-1 vaccines and adaptive trial designs.

Developing a vaccine against the human immunodeficiency virus (HIV) poses an exceptional challenge. There are no documented cases of immune-mediated clearance of HIV from an infected individual, and no known correlates of immune protection. Although nonhuman primate models of lentivirus infection have provided valuable data about HIV pathogenesis, such models do not predict HIV vaccine efficacy in humans. The combined lack of a predictive animal model and undefined biomarkers of immune protection against HIV necessitate that vaccines to this pathogen be tested directly in clinical trials. Adaptive clinical trial designs can accelerate vaccine development by rapidly screening out poor vaccines while extending the evaluation of efficacious ones, improving the characterization of promising vaccine candidates and the identification of correlates of immune protection.

Coping with an HIV infection. A multicenter qualitative survey on HIV positive adolescents' perceptions of their disease, therapeutic adherence and treatment.

HIV-positive adolescents face a number of challenges in dealing with their disease and its treatment. In this qualitative study, twenty-nine HIV-positive adolescents aged 13 to 20 years (22 girls), who live in Switzerland, were asked, in a semi-structured interview (duration of 40-110 minutes), to describe their perceptions and experiences with the disease itself and with therapeutic adherence. While younger adolescents most often thought of their disease as fate, older adolescents usually knew that they had received it through vertical transmission, although the topic appeared to be particularly difficult to discuss for those living with their HIV-positive mothers. Based on their attending physician's assessment, 18 subjects were judged highly adherent, 4 fairly and 7 poorly adherent. High adherence appeared linked with adequate psychological adjustment and effective coping mechanisms, as well as with the discussion and adoption of explicit medication-taking strategies. The setting and organisation of health care teams should allow for ongoing discussions with HIV-positive adolescents that focus on their perceptions of their disease, how they cope with it and with the treatment, and how they could improve their adherence.

Reasons for late presentation to HIV care in Switzerland.

INTRODUCTION: Late presentation to HIV care leads to increased morbidity and mortality. We explored risk factors and reasons for late HIV testing and presentation to care in the nationally representative Swiss HIV Cohort Study (SHCS). METHODS: Adult patients enrolled in the SHCS between July 2009 and June 2012 were included. An initial CD4 count <350 cells/µl or an AIDS-defining illness defined late presentation. Demographic and behavioural characteristics of late presenters (LPs) were compared with those of non-late presenters (NLPs). Information on self-reported, individual barriers to HIV testing and care were obtained during face-to-face interviews. RESULTS: Of 1366 patients included, 680 (49.8%) were LPs. Seventy-two percent of eligible patients took part in the survey. LPs were more likely to be female (p<0.001) or from sub-Saharan Africa (p<0.001) and less likely to be highly educated (p=0.002) or men who have sex with men (p<0.001). LPs were more likely to have their first HIV test following a doctor's suggestion (p=0.01), and NLPs in the context of a regular check-up (p=0.02) or after a specific risk situation (p<0.001). The main reasons for late HIV testing were "did not feel at risk" (72%), "did not feel ill" (65%) and "did not know the symptoms of HIV" (51%). Seventy-one percent of the participants were symptomatic during the year preceding HIV diagnosis and the majority consulted a physician for these symptoms. CONCLUSIONS: In Switzerland, late presentation to care is driven by late HIV testing due to low risk perception and lack of awareness about HIV. Tailored HIV testing strategies and enhanced provider-initiated testing are urgently needed.

An inhibitor of HIV-1 protease modulates constitutive eIF2α dephosphorylation to trigger a specific integrated stress response.

Inhibitors of the HIV aspartyl protease [HIV protease inhibitors (HIV-PIs)] are the cornerstone of treatment for HIV. Beyond their well-defined antiretroviral activity, these drugs have additional effects that modulate cell viability and homeostasis. However, little is known about the virus-independent pathways engaged by these molecules. Here we show that the HIV-PI Nelfinavir decreases translation rates and promotes a transcriptional program characteristic of the integrated stress response (ISR). Mice treated with Nelfinavir display hallmarks of this stress response in the liver, including α subunit of translation initiation factor 2 (eIF2α) phosphorylation, activating transcription factor-4 (ATF4) induction, and increased expression of known downstream targets. Mechanistically, Nelfinavir-mediated ISR bypassed direct activation of the eIF2α stress kinases and instead relied on the inhibition of the constitutive eIF2α dephosphorylation and down-regulation of the phophatase cofactor CReP (Constitutive Repressor of eIF2α Phosphorylation; also known as PPP1R15B). These findings demonstrate that the modulation of eIF2α-specific phosphatase cofactor activity can be a rheostat of cellular homeostasis that initiates a functional ISR and suggest that the HIV-PIs could be repositioned as therapeutics in human diseases to modulate translation rates and stress responses.

Patients' understanding of blood tests and attitudes to HIV screening in the emergency department of a Swiss teaching hospital: a cross-sectional observational study.

BACKGROUND: In Switzerland, patients may undergo "blood tests" without being informed what these are screening for. Inadequate doctor-patient communication may result in patient misunderstanding. We examined what patients in the emergency department (ED) believed they had been screened for and explored their attitudes to routine (non-targeted) human immunodeficiency virus (HIV) screening. METHODS: Between 1st October 2012 and 28th February 2013, a questionnaire-based survey was conducted among patients aged 16-70 years old presenting to the ED of Lausanne University Hospital. Patients were asked: (1) if they believed they had been screened for HIV; (2) if they agreed in principle to routine HIV screening and (3) if they agreed to be HIV tested during their current ED visit. RESULTS: Of 466 eligible patients, 411 (88%) agreed to participate. Mean age was 46 ± 16 years; 192 patients (47%) were women; 366 (89%) were Swiss or European; 113 (27%) believed they had been screened for HIV, the proportion increasing with age (p ≤0.01), 297 (72%) agreed in principle with routine HIV testing in the ED, and 138 patients (34%) agreed to be HIV tested during their current ED visit. CONCLUSION: In this ED population, 27% believed incorrectly they had been screened for HIV. Over 70% agreed in principle with routine HIV testing and 34% agreed to be tested during their current visit. These results demonstrate willingness among patients concerning routine HIV testing in the ED and highlight a need for improved doctor-patient communication about what a blood test specifically screens for.

24/12/19 Vel d'Hiv' départ du Bol d'or [les pistards : Georget, Van Neh, Deruyter, Godivier, Bartelemy, Léonard et Steux] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57305

25-12-19 Vel d'Hiv', Bol d'or [les pistards au repos] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57307

Vel d'Hiv' 25/12/19, [Léon] Georget vainqueur du Bol d'or : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57311

[25-12-19 Vel d'Hiv'] Barthelemy 4e, Georget vainqueur du Bol d'or, Godivier 2e : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57313

Will the "fight" ever end? : a critical reading of the metaphors and discourses that construct HIV/AIDS in an African context

In this thesis, I critically examine the discourses that inform how we conceptualise HIV/AIDS in Sub-Saharan Africa as they are produced in a sample of Canadian news articles, two nonfiction texts - Stephanie Nolen's 28 Stories of AIDS in Africa and Jonathan Morgan and the Bambanani Women's Group's Long Life ... Positive HIV Stories - as well as two literary texts - John Le Carre's popular fiction novel The Constant Gardener and an anthology of stories and poems from Southern Africa titled Nobody Ever Said AIDS, compiled and edited by Nobantu Rasebotsa, Meg Samuelson and Kylie Thomas. Paying particular attention to the role of metaphor in discursive formation, I have found that military metaphors, usually used in conjunction with biomedical discourses, continue to dominate what is said about HIV/AIDS. However, the use of military metaphors to conceptualise HIV/AIDS contributes to stigma and limits the effectiveness of responses to the pandemic. I argue that accessing alternative metaphors and discourses, such as biopsychosocial discourse, can lead to a more layered - and more beneficial - conceptualisation of HIV/AIDS, encouraging a more active response to the pandemic.

Relationship between Socio-Demographic Factors and Familial and Partner Pressures to Conceive in HIV-Positive Women in Ontario

This study examined the relationship between socio-demographic factors and family and partner pressure to conceive in women living with HIV in Ontario, Canada. A total of 490 women, aged 18-52 years were included in the study. The HIV Pregnancy Planning Questionnaire was used to collect data on socio-demographic, medical, and pressure variables. Multivariate logistic regression analysis suggest that increased age, years lived in Canada, and living in Toronto were associated with lower odds, and being married and having 0-1 lifetime births were associated with higher odds of family pressure to conceive. Increased age was associated with lower odds, and being married and living in Toronto were associated with higher odds of partner pressure to conceive. Findings suggest that socio-demographic factors influence the fertility decision-making process. Health care providers should consider socio-demographic factors along with medical factors when assisting women living with HIV and their partners to make informed reproductive decisions.

Aboriginal status is a prognostic factor for mortality among antiretroviral naïve HIV-positive individuals first initiating HAART

Affiliation: Mark Daniel: Département de médecine sociale et préventive, Faculté de médecine, Université de Montréal et Centre de recherche du Centre hospitalier de l'Université de Montréal

Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import

Affiliation: Zhujun Ao, Éric Cohen & Xiaojian Yao : Département de microbiologie et immunologie, Faculté de Médecine, Université de Montréal

Analysis of HIV-1 Vpr determinants responsible for cell growth arrest in Saccharomyces cerevisiae

Affiliation: Département de microbiologie et immunologie, Faculté de médecine, Université de Montréal