Investigation of HIV Incidence Rates in a High-Risk, High-Prevalence Kenyan Population: Potential Lessons for Intervention Trials and Programmatic Strategies

Abstract Cost-effective HIV prevention programs should target persons at high risk of HIV acquisition. We conducted an observational HIV incidence cohort study in Kisumu, Kenya, where HIV prevalence is triple that of the national rate. We used referral and venue-sampling approaches to enroll HIV-negative persons for a 12-month observational cohort, August 2010 to September 2011, collected data using computer-assisted interviews, and performed HIV testing quarterly. Among 1292 eligible persons, 648 (50%) were excluded for HIV positivity and other reasons. Of the 644 enrollees, 52% were women who were significantly older than men (P < .01). In all, 7 persons seroconverted (incidence rate [IR] per 100 person-years ¼ 1.11; 95% confidence interval [CI] 0.45-2.30), 6 were women; 5 (IR ¼ 3.14; 95% CI 1.02-7.34) of whom were 25 years. Most new infections occurred in young women, an observation consistent with other findings in sub-Saharan Africa that women aged 25 years are an important population for HIV intervention trials in Africa

Impact of route and adequacy of nutritional intake on outcomes of allogeneic haematopoietic cell transplantation for haematologic malignancies.

BACKGROUND: Allogeneic haematopoietic cell transplantation (HCT) is often associated with poor oral intake due to painful mucositis and gastrointestinal sequalae that occur following a preparative regimen of intensive chemotherapy and/or total body radiation. Although attractive to assume that optimal nutrition improves HCT outcomes, there are limited data to support this. It is also unclear whether artificial nutrition support should be provided as enteral tube feeding or parenteral nutrition (PN). METHODS: We analysed day-100 non-relapse mortality (NRM), incidence of acute graft-versus-host disease (GvHD), acute gastrointestinal GvHD, 5-year survival and GvHD-free/relapse-free survival (GRFS) according to both route and adequacy of nutritional intake prior to neutrophil engraftment, together with other known prognostic factors, in a retrospective cohort of 484 patients who underwent allogeneic HCT for haematologic malignancy between 2000 and 2014. RESULTS: Multivariate analyses showed increased NRM with inadequate nutrition (hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.2-7.2) and adequate PN (HR 2.9; 95% CI 1.6-5.4) compared to adequate enteral nutrition (EN) both P < .001. There were increased incidences of gastrointestinal GvHD of any stage and all GvHD ≥ grade 2 in patients who received PN (odds ratio (OR) 2.0; 95% CI 1.2-3.3; P = .006, and OR 1.8; 95% CI 1.1-3.0; P = .018, respectively), compared to adequate EN. Patients who received adequate PN and inadequate nutrition also had reduced probabilities of survival and GRFS at 5 years. CONCLUSION: Adequate EN during the early transplantation course is associated with reduced NRM, improved survival and GRFS at 5 years. Furthermore, adequate EN is associated with lower incidence of overall and gut acute GvHD than PN, perhaps because of its ability to maintain mucosal integrity, modulate the immune response to intensive chemo/radiotherapy and support the gastrointestinal tract environment, including gut microflora

Randomized controlled phase IIa clinical trial of safety, pharmacokinetics and pharmacodynamics of tenofovir and tenofovir plus levonorgestrel releasing intravaginal rings used by women in Kenya

IntroductionGlobally, many young women face the overlapping burden of HIV infection and unintended pregnancy. Protection against both may benefit from safe and effective multipurpose prevention technologies.MethodsHealthy women ages 18–34 years, not pregnant, seronegative for HIV and hepatitis B surface antigen, not using hormonal contraception, and at low risk for HIV were randomized 2:2:1 to continuous use of a tenofovir/levonorgestrel (TFV/LNG), TFV, or placebo intravaginal ring (IVR). In addition to assessing genital and systemic safety, we determined TFV concentrations in plasma and cervicovaginal fluid (CVF) and LNG levels in serum using tandem liquid chromatography-mass spectrometry. We further evaluated TFV pharmacodynamics (PD) through ex vivo CVF activity against both human immunodeficiency virus (HIV)-1 and herpes simplex virus (HSV)-2, and LNG PD using cervical mucus quality markers and serum progesterone for ovulation inhibition.ResultsAmong 312 women screened, 27 were randomized to use one of the following IVRs: TFV/LNG (n = 11); TFV-only (n = 11); or placebo (n = 5). Most screening failures were due to vaginal infections. The median days of IVR use was 68 [interquartile range (IQR), 36–90]. Adverse events (AEs) were distributed similarly among the three arms. There were two non-product related AEs graded &gt;2. No visible genital lesions were observed. Steady state geometric mean amount (ssGMA) of vaginal TFV was comparable in the TFV/LNG and TFV IVR groups, 43,988 ng/swab (95% CI, 31,232, 61,954) and 30337 ng/swab (95% CI, 18,152, 50,702), respectively. Plasma TFV steady state geometric mean concentration (ssGMC) was &lt;10 ng/ml for both TFV IVRs. In vitro, CVF anti-HIV-1 activity showed increased HIV inhibition over baseline following TFV-eluting IVR use, from a median of 7.1% to 84.4% in TFV/LNG, 15.0% to 89.5% in TFV-only, and −27.1% to −20.1% in placebo participants. Similarly, anti-HSV-2 activity in CVF increased &gt;50 fold after use of TFV-containing IVRs. LNG serum ssGMC was 241 pg/ml (95% CI 185, 314) with rapid rise after TFV/LNG IVR insertion and decline 24-hours post-removal (586 pg/ml [95% CI 473, 726] and 87 pg/ml [95% CI 64, 119], respectively).ConclusionTFV/LNG and TFV-only IVRs were safe and well tolerated among Kenyan women. Pharmacokinetics and markers of protection against HIV-1, HSV-2, and unintended pregnancy suggest the potential for clinical efficacy of the multipurpose TFV/LNG IVR.Clinical Trial RegistrationNCT03762382 [https://clinicaltrials.gov/ct2/show/NCT03762382

Mechanisms of tumour progression in indolent B lymphoid haemopathies : applications to Waldenström dysglobulinemia and Chronic Lymphocytic Leukemia

Résumé indisponible.Résumé indisponible

State-of-the-art for CAR T-cell therapy for chronic lymphocytic leukemia in 2019

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De la nutrition artificielle au cours de l'allogreffe de cellules souches hématopoïétiques (résultats d'une étude rétrospective monocentrique, construction d'un essai clinique prospectif randomisé multicentrique et d'un projet d'exploration du rôle potentiel du microbiote dans la modulation du devenir post-allogreffe)

L'allogreffe de Cellules Souches Hématopoïétiques (CHS) est une procédure lourde, grevée d'une toxicité non négligeable. Un support nutritionnel artificiel est indispensable pendant son déroulement, mais les modalités optimales n'en sont pas connues. Les données récentes de la littérature suggèrent un bénéfice à l'emploi systématique de la nutrition entérale (NE) vs la Nutrition Parentérale (NP), notamment sur l'incidence des complications infectieuses et immunologiques précoces. Les résultats de notre étude rétrospective locale, menée sur 56 patients allogreffés au CHU de Clermont-Ferrand, sont en faveur d'une diminution du risque infectieux précoce avec l'emploi de la NE. Ils montrent également l'équivalence de la NE et de la NP en termes d'efficacité nutritionnelle chez des patients lourdement traités dont les capacités d'absorption digestive sont souvent remises en cause. Ces résultats mettent en exergue les mesures à mettre en oeuvre, en amont et pendant la prise en charge nutritionnelle, pour améliorer l'acceptation et la tolérance de la nutrition entérale dans ce contexte particulier qu'est l'allogreffe de CSH. Létude des données de la littérture et les ésultats de notre étude monocentrique ont permis de construire et de faire évoluer le projet d'essai clinique prospectif NEPHA (Etude prospective, randomisée, multicentrique, comparant la Nutrition Entérale et la nutrition Parentérale comme support nutritionnel chez les malades atteints d'Hémopathie maligne traités par Allogreffe de cellules souches hématopoïtiques), dont le CHU de Clermont-Ferrand est le promoteur, et qui fait l'objet d'un financement dans le cadre des PHRC nationaux de l'INCA (2002). Les inclusions devraient débuter en septembre 2013. Enfin, les données issues de l'étude spécialisée des caractéristiques de microbiote digestif dans ce contexte pourraient permettre d'apporter un support mécanistique à la supériorité potentielle de la nutrition entérale.CLERMONT FD-BCIU-Santé (631132104) / SudocSudocFranceF

Pomalidomide dans les myélomes multiples

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Les CAR-T cells sont là !

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Characterization of the novel HLA‐B *56:76 allele by sequencing‐based typing

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Characterization of the novel HLA‐A *29:02:38 allele by sequencing‐based typing

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