Nouvelles recommandations de dépistage du VIH en population générale (état des lieux des pratiques des médecins généralistes en 2013 à Marseille d'après une étude transversale)

OBJECTIF: Faire un état des lieux des pratiques des médecins généralistes à Marseille en matière de dépistage du VIH en population générale suite à la parution des dernières recommandations de l'HAS. MATERIEL ET METHODES: Une enquête transversale effectuée de janvier à mars 2013 auprès de 462 généralistes marseillais à partir d'un questionnaire visant à évaluer leurs pratiques. Analyse statistique descriptive et des données croisées. RESULTATS: 37% de réponses obtenues réparties sur les 16 arrondissements de la ville. Les médecins interrogés connaissent bien les recommandations de l'HAS de dépistage de VIH qui ont eu pour plus de la moitié d'entre eux un impact sur les prescription de test VIH. Néanmoins le dépistage systématique en population générale n'est pas assez appliqué et de nombreux freins semblent évidents. Ces recommandations ne sont pas bien applicables et pas forcément cout-efficaes. Les généralistes sont ipliqués et volontaires et reconnaissent leur place centrale mais ont besoin d'une dépistage ciblé sur certaines populations à risque était indispensable et qu'une bonne identification de ces populations à risque était primordiale. CONCLUSION: Il faut prioriser et nuancer les recommandations de l'HAS afin de proposer le dépistage VIH de façon ciblée et généralisée, renforcer les liens entre généralistes et spécialistes, diversifier les outils et les lieux de dépistage et sensibiliser le grand public à l'intérêt d'un dépistage élargi.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Impact of tenofovir dose adjustment on both estimated glomerular filtration rate and tenofovir trough concentration

International audienceBackground: Tenofovir disoproxil fumarate (TDF)-based regimen is a treatment option for HIV-infected patients. TDF dose adjustment is recommended in patients with impaired renal function. We assessed the impact of TDF dose adjustment on renal function and tenofovir trough concentration.& para;& para;Methods: Fourteen HIV patients for whom TDF dose was adjusted (1 tablet/48 h) because of estimated glomerular filtration rate (eGFR) 90 ng/ml between 2006 and 2013 were selected. The eGFR was measured at baseline and 3, 6 and 12 months after TDF dose adjustment.& para;& para;Results: A 50% TDF dose reduction resulted in a significant increase of the eGFR 3 months after dose adjustment (61.1 versus 72.8 ml/min/1.73 m(2); P=0.003). Concomitantly, tenofovir trough concentration decreased from 175 to 66 ng/ml (P=0.009). Antiviral efficacy was maintained in all patients.& para;& para;Conclusions: TDF dose adjustment combined with therapeutic drug monitoring may be useful especially in patients at risk of kidney dysfunction

Cancer risk in HIV-infected patients

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Frailty in HIV infected people: a new risk factor for bone mineral density loss

International audienceObjective: The study aims to assess the association between bone mineral density (BMD) and frailty in a cohort of HIV-infected patients. Design: A cross-sectional study in an HIV outpatient unit where nearly 1000 patients are monitored. Methods: Study participants undergoing bone densitometry were proposed an evaluation of frailty using criteria of the Cardiovascular Health Study (CHS) and the Study of Osteoporotic Fractures (SOF). Frailty markers were weight-loss, self-reported exhaustion , physical activity, grip strength, chair stands, and slow gait. Patients' characteristics were collected from an electronic medical record. Associations of frailty with BMD and osteoporosis were tested using multivariate linear and logit regression models, respectively. Results: In total, 175 HIV-infected patients, 121 (69.14%) men, were analyzed. Prevalence of frailty markers, osteopenia, and osteoporosis were comparable among sexes. Despite a younger age, spinal and femoral neck BMD were lower in women (P < 0.05). Linear regression model adjusting by age, duration of HIV follow-up, BMI, smoking status, osteoarthritis, osteoporosis treatment, and the age at menopause showed a negative association of spinal and femoral BMD with frailty according to SOF criteria in women (P < 0.05). In men, SOF-defined frailty was associated with osteoporosis (odds ratio 28.79; 95% confidence interval 2.15-386.4) in a model adjusting for age, duration of HIV follow-up, CD4 þ nadir, CD4 þ T-cell count, tobacco consumption, exposure to tenofovir (TDF) and protease inhibitors. No significant associations were found between BMD and CHS-defined frailty. Conclusion: Our study shows that frailty according to SOF criteria is associated with low spinal BMD values in female and osteoporosis in male HIV-infected patients

Impact of hepatitis C virus coinfection on T-cell dynamics in long-term HIV-suppressors under combined antiretroviral therapy

International audienceObjective: The objective of this study is to evaluate the impact of hepatitis C virus (HCV) serostatus on the evolution of CD8 þ cells and CD4 þ : CD8 þ ratio in HIV-infected patients on combined antiretroviral therapy (cART) who achieve sustained undetectable viral load (HIV-pVL). Design and methods: A longitudinal study performed in an outpatient HIV-unit following 1495 HIV-infected patients. Data of patients on cART achieving undetectable HIV-pVL for at least 3 years were collected retrospectively from our medical e-database NADIS from January 1997 to April 2005, a period defined in order to select patients who were naive of hepatitis treatment. T-cell counts were assessed every 6 months from HIVsuppression over the study period. Results: Two hundred and twenty-six HIV mono-infected (group 1) and 130 HCVcoinfected patients (group 2; genotype prevalence: 42% HCV-G1, 26% HCV-G3, 11% HCV-G4 and 21% HCV-G2) fulfilled the selection criteria. cART regimens were comparable between the groups, as were CD4 þ and CD8 þ cell counts at the first undetectable HIV-pVL. After 3 years, both groups displayed similar CD4 þ cell reconstitution, although CD4 þ percentage was higher in group 1 (30.3 AE 1.1 vs. 27 AE 1.1%; P < 0.001). HIV suppression led to a significant drop of median CD8 þ cell counts in group 1 (P ¼ 0.027), but not in group 2, which displayed higher CD8 þ cell counts all through the follow-up (mean diff. ¼ 135.71 AE 26.89 cells/ml, P < 0.001). Moreover, the fraction of patients reaching CD4 þ : CD8 þ ratio ! 1 was lower in group 2 (14 vs. 27.7%; P < 0.05). Conclusion: Despite sustained HIV suppression under cART, HCV coinfection was found to hamper CD8 þ downregulation. Further studies will determine the impact of treatment with direct-acting antiviral agents on the CD8 þ pool, and the advantage of systematic HCV-targeted therapy for HIV/HCV-coinfected patients

Severe Pulmonary Arterial Hypertension in Patients Treated for Hepatitis C With Sofosbuvir

International audienceDevelopment of direct-acting antiviral agents against hepatitis C virus (HCV) has changed the management of chronic HCV infection. We report three cases of newly diagnosed or exacerbated pulmonary arterial hypertension (PAH) in patients treated with sofosbuvir. All patients had PAH-associated comorbidities (HIV coinfection in two, portal hypertension in one) and one was already being treated for PAH. At admission, all patients presented with syncope, World Health Organization functional class IV, right-sided heart failure, and extremely severe hemodynamic parameters. After specific PAH therapy, the clinical and hemodynamic properties for all patients were improved. Severity and acuteness of PAH, as well as chronology, could suggest a causal link between HCV treatment and PAH onset. We hypothesize that suppression of HCV replication promotes a decrease in vasodilatory inflammatory mediators leading to worsening of underlying PAH. The current report suggests that sofosbuvir-based therapy may be associated with severe PAH

Therapeutic Perspectives in the Systemic Treatment of Kaposi’s Sarcoma

International audienceIn patients with Kaposi’s sarcoma (KS), the therapeutic goal is to achieve a durable remission in the size and number of skin and visceral lesions. Although most patients show tumor regression in response to standard systemic chemotherapy regimens, alternative systemic treatments are needed for patients who develop refractory KS. Anti-angiogenic therapies represent attractive therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis. Pomalidomide, which exhibits such anti-angiogenic activity through inhibition of VEGF, currently constitutes the most promising agent of this class and has been recently approved by the FDA. In addition, immune checkpoint blockade also represents an interesting alternative therapeutic approach through the restoration of immunity against HHV-8, the causative agent of KS, and improvement of tumor control. Although small series of cases treated successfully with these drugs have been reported, there is no marketing approval for anti-immune checkpoint antibodies for KS to date. In the present review, we will discuss potential therapeutic options for patients with recurrent or refractory KS, including systemic chemotherapies, immune checkpoint inhibitors, anti-herpesvirus agents, and anti-angiogenic drugs. Well-conducted clinical trials in this population are urgently needed to correctly address the efficacy of targeted agents and immunomodulators, while monitoring for adverse effects