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Meudon, France

Piketty C.,AP HP Service dImmunologie Clinique | Cochand-Priollet B.,University Denis Diderot | Lanoy E.,French Institute of Health and Medical Research | Lanoy E.,University 06 S 943 | And 10 more authors.
AIDS | Year: 2013

BACKGROUND: A high prevalence of anal squamous intraepithelial lesions (ASIL) and human papillomavirus (HPV) infections were observed in HIV-infected men who have sex with men (MSM) in the precART (combined antiretroviral therapy) era. The impact of cART on the natural history of HPV infection and ASIL is poorly documented. METHODS: Ninety-four HIV-infected MSM naive of cART were enrolled in a longitudinal study before starting cART. Patients were evaluated for anal cytology, histology and anal HPV DNA at baseline, month 12 and month 24 of cART. HPV DNA genotyping was performed by Linear Array assay. Anal cytologic samples were processed by the Thin Prep method. RESULTS: Analyses included 76 patients with at least two visits with available cytology. The median age was 39.4 years. The median (interquartile range) CD4 cell count was 301 cells/μl (242-339) at baseline and 545 cells/μl at month 24, when 93% of patients had plasma HIV-RNA 50copies/ml or less. An abnormal result was observed in 45 of 76 patients at baseline (59%) with prevalent low-grade squamous intraepithelial lesion (LSIL) in 27 patients (36%) and high-grade squamous intraepithelial lesion (HSIL) in seven patients (9%) and in 36 of 69 patients assessed at month 24 (52%) with LSIL in 23 patients (33%) and HSIL in six patients (9%). At month 24, regression of the severity of lesions was observed in 44% of patients, whereas a lesion occurred in 37% of patients. CONCLUSION: Our results show a high prevalence and incidence of ASIL in HIV-infected MSM despite immune restoration under cART. These data emphasize that HIV-positive MSM although receiving effective cART remain at high risk of anal squamous intra-epithelial lesions. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Launay O.,University of Paris Descartes | Launay O.,French Institute of Health and Medical Research | Desaint C.,University of Paris Descartes | Desaint C.,French Institute of Health and Medical Research | And 16 more authors.
Journal of Infectious Diseases | Year: 2011

Background. Human immunodeficiency virus (HIV)-infected patients have decreased immune response to vaccines. Few data are available about pandemic flu vaccination in this population. Methods. We conducted amulticenter, patient-blinded, randomized trial in a cohort of HIV-infected adults. Patients received 2 injections 21 days apart of a AS03A-adjuvanted H1N1v vaccine containing 3.75 μg hemagglutinin (HA) or a nonadjuvanted H1N1v vaccine containing 15 μg HA to assess hemagglutination inhibition (HI) response and safety. Results. A total of 309 patients were randomized, and 306 were vaccinated. After the first vaccine dose, HI titers ≥1:40 were observed in 93.4% of the patients in the adjuvanted group (A group) (n = 155) and in 75.5% in the nonadjuvanted group (B group) (n = 151) (P < .001); seroconversion rates were 88.8% and 71.2%, and factor increases in geometric mean titers (GMT) of 21.9 and 15.1, respectively. After 2 injections, 98.6% of patients of the A group and 92.1% of the B group demonstrated HI titers ≥1:40 (P = .018); seroconversion rates were 96.5% and 87.1%, respectively, and factor increases in GMT were 45.5 and 21.2, respectively. The majority of adverse events were mild to moderate in severity; no impact on CD4+ cell count or viral load has been detected. Conclusions. In HIV-1-infected adults, the AS03 A-adjuvanted H1N1v vaccine yielded a higher immune response than did the nonadjuvanted one, with no impact on HIV infection.

Levy C.,SFP Societe Francaise de Pediatrie | Taha M.-K.,Institute Pasteur Paris | Bingen E.,SFP Societe Francaise de Pediatrie | Bingen E.,University Denis Diderot | And 2 more authors.
Archives de Pediatrie | Year: 2012

Background: The GPIP/ACTIV (Groupe de Pathologie Infectieuse Pédiatrique and Association Clinique et Thérapeutique Infantile du Val de Marne) set up an active surveillance network to analyze the epidemiological, clinical and biological features of meningococcal meningitis. Methods: French pediatric wards working with 166 microbiology laboratories enrolled all children (0-18 years old) with bacterial meningitis. Risk factors, signs and symptoms, vaccination status, cerebrospinal fluid analysis, treatments and case fatality rate were recorded. Results: Since 2001, 1661 meningococcal meningitis were reported among 3769 (44.1%) bacterial meningitis. Mean age was 4.4- year- old (±4.8, median 2.5) and 2/3 cases occurred in children under 5- year- old (68.8%). Serogroup B (61.3%) is preponderant following by serogroup C (27.0%). 27.5% of children had received an antibiotic treatment 24 hours before lumbar puncture. A shock is reported in 31.0% of cases. No cases of meningococcal meningitis C has been reported in children vaccinated with a conjugate vaccine. Two children vaccinated with MenBvac® vaccine had a meningitis B14:P1.7,16. Global case fatality rate was 6.5% but was higher (9.2%) for serogroup C than for serogroup B (5.9%) (p=0.02). Conclusion: This is among the largest series of microbiologically documented meningococcal meningitis to date (1661 cases). In France, meningococal is responsible for approximately 50 % of meningitis. Effective meningococcal serogroup B vaccine and serogroup C vaccination recommendation could control the burden of meningococal meningitis. © 2012 Elsevier Masson SAS.

Pascoli V.,University of Geneva | Cahill E.,University Pierre and Marie Curie | Bellivier F.,LAssistance Publique Hopitaux de Paris | Bellivier F.,University Denis Diderot | And 3 more authors.
Biological Psychiatry | Year: 2014

Addiction is a chronic and relapsing psychiatric disorder that is thought to occur in vulnerable individuals. Synaptic plasticity evoked by drugs of abuse in the so-called neuronal circuits of reward has been proposed to underlie behavioral adaptations that characterize addiction. By increasing dopamine in the striatum, addictive drugs alter the balance of dopamine and glutamate signals converging onto striatal medium-sized spiny neurons (MSNs) and activate intracellular events involved in long-term behavioral alterations. Our laboratory contributed to the identification of salient molecular changes induced by administration of addictive drugs to rodents. We pioneered the observation that a common feature of addictive drugs is to activate, by a double tyrosine/threonine phosphorylation, the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the striatum, which control a plethora of substrates, some of them being critically involved in cocaine-mediated molecular and behavioral adaptations. Herein, we review how the interplay between dopamine and glutamate signaling controls cocaine-induced ERK1/2 activation in MSNs. We emphasize the key role of N-methyl-D-aspartate receptor potentiation by D1 receptor to trigger ERK1/2 activation and its subsequent nuclear translocation where it modulates both epigenetic and genetic processes engaged by cocaine. We discuss how cocaine-induced long-term synaptic and structural plasticity of MSNs, as well as behavioral adaptations, are influenced by ERK1/2-controlled targets. We conclude that a better knowledge of molecular mechanisms underlying ERK1/2 activation by drugs of abuse and/or its role in long-term neuronal plasticity in the striatum may provide a new route for therapeutic treatment in addiction.

Mandelbrot L.,University Denis Diderot | Berrebi A.,Toulouse University Hospital Center | Rouzioux C.,Service de Virologie | Partisani M.,COREVIH | And 5 more authors.
Gynecologie Obstetrique Fertilite | Year: 2014

The desire for children is a legitimate aspiration that should be part of multidisciplinary care for all men, women or couples living with HIV. The use of effective antiretroviral therapy has revolutionized the prevention of sexual, as well as mother-to-child HIV transmission. When the HIV plasma viral load is undetectable on long-term antiretroviral therapy, the risk of mother-to-child transmission is <1% and the risk of heterosexual HIV transmission without condom use in a stable relationship is very low (estimated at less than 1/10,000) in the absence of inflammation of the genital tract. In a man with a long-term undetectable viral load, viral shedding in semen is uncommon, but may occur persistently or intermittently. The same appears true of viral shedding in the vaginal tract of women. Reproductive options are: natural conception, self-insemination when the woman is HIV-infected, assisted reproduction. Natural conception is now considered to be an acceptable option when the conditions are met, after exploring four aspects: (1) virological (viral load undetectable sustained for at least 6 months on therapy), (2) genital (absence of genital infections or lesions), (3) fertility (after appropriate evaluation) and (4) detecting the ovulation period to limit intercourse without condoms. Assisted reproduction has two objectives in the context of HIV, to allow the couple to conceive without abandoning condom use and/or to treat infertility. © 2014 Elsevier Masson SAS. All rights reserved.

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