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International audience; Antibiotic treatment of native osteomyelitis caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) is a challenge. Limited epidemiological and outcome data are available. This retrospective cohort study included osteomyelitis patients with ESBL-PE infections treated in a reference centre for bone and joint infections (BJIs) between 2011–2019. Twenty-nine patients with native BJI (mean age, 44.4 ± 15.7 years) were analysed. Fifteen cases were paraplegic patients with ischial pressure sores breaching the hip capsule. Other cases included eight other hip infections, four tibial infections and two foot infections. Infections were mostly polymicrobial (n = 23; 79.3%), including Staphylococcus aureus (n = 13; 8 methicillin-resistant). Klebsiella pneumoniae (n = 13) was the most frequent ESBL-producing species identified, followed by Escherichia coli (n = 10), including 3 E. coli/K. pneumoniae co-infections, and Enterobacter spp. (n = 9). ESBL-PE were rarely susceptible to fluoroquinolones (n = 4; 13.8%). Most therapies were based on carbapenems (n = 22) and combination therapies (n = 19). The median duration of treatment was 41 (5–60) days. Primary control of the infection was achieved in 62.1% (18/29) of cases and up to 86.2% after second look surgeries, after a median follow-up of 6 (1–36) months. Infection with ESBL-producing K. pneumoniae was associated with failure (P = 0.001), whereas age, infection location, prior colonisation and antimicrobial therapy were not found to be predictors of outcome. ESBL-PE native BJIs are often polymicrobial and fluoroquinolone-resistant infections caused by K. pneumoniae, highlighting the need for expert centres with pluridisciplinary meetings with experienced surgeons.

Background It is unclear whether HIV infection affects the long‐term prognosis after an acute coronary syndrome (ACS). The objective of the current study was to compare rates of major adverse cardiac and cerebrovascular events after a first ACS between people living with HIV (PLHIV) and HIV‐uninfected (HIV−) patients, and to identify determinants of cardiovascular prognosis. Methods and Results Consecutive PLHIV and matched HIV− patients with a first episode of ACS were enrolled in 23 coronary intensive care units in France. Patients were matched for age, sex, and ACS type. The primary end point was major adverse cardiac and cerebrovascular events (cardiac death, recurrent ACS, recurrent coronary revascularization, and stroke) at 36‐month follow‐up. A total of 103 PLHIV and 195 HIV− patients (mean age, 49 years [SD, 9 years]; 94.0% men) were included. After a mean of 36.6 months (SD, 6.1 months) of follow‐up, the risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV− patients (17.8% and 15.1%, P =0.22; multivariable hazard ratio [HR], 1.60; 95% CI, 0.67–3.82 [ P =0.29]). Recurrence of ACS was more frequent among PLHIV (multivariable HR, 6.31; 95% CI, 1.32–30.21 [ P =0.02]). Stratified multivariable Cox models showed that HIV infection was the only independent predictor for ACS recurrence. PLHIV were less likely to stop smoking (47% versus 75%; P =0.01) and had smaller total cholesterol decreases (–22.3 versus –35.0 mg/dL; P =0.04). Conclusions Although the overall risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV− individuals, PLHIV had a higher rate of recurrent ACS. Registration URL: https://www.clini​caltr​ials.gov ; Unique identifier: NCT00139958.

Introduction et but de l’etude L’anorexie mentale (AM) est la pathologie psychiatrique avec le plus haut taux de mortalite, notamment a cause de la denutrition. L’immunodepression cellulaire induite par cette denutrition severe pourrait etre a l’origine de l’apparition d’infections pulmonaires chroniques opportunistes (IPCO). Seuls quelques cas d’IPCO dans l’AM ont ete rapportes dans la litterature. Le but de cette etude etait d’identifier les facteurs associes aux IPCO dans une population de patients denutris atteints d’AM. Materiel et methodes Une etude observationnelle a ete realisee dans un service soins tertiaires dedie aux patients atteints d’AM et severement denutris. Le diagnostic d’IPCO a ete fait sur la presence de lesions suggestives au scanner thoracique, associe ou non a une identification microbiologique. Chaque patient avec un diagnostic d’IPCO a ete apparie sur l’âge et le sexe a deux patients non malades, hospitalises au cours de la meme periode. Les variables suivantes ont ete recueillies : poids, IMC, CRP, albuminemie, transthyretine, neutrophiles, lymphocytes, et identification des germes a la culture des expectorations le cas echeant. Le test t de Student et la regression logistique ont ete effectues pour determiner les parametres associes aux IPCO. Une analyse discriminante et des courbes de ROC ont ete realisees pour les variables significatives en univariee. Resultats et analyse statistique Entre 2004 et 2020, 1441 patients ont ete hospitalises et 31 avaient un diagnostic d’IPCO (2,2 %). Les patients atteints d’IPCO avaient un IMC inferieur (11,5 vs 13,0 ; p = 0,02), un taux de lymphocytes sanguins plus bas (763 vs 1637/mm3 ; p Conclusion L’IPCO est une des complications somatiques observees chez les patients avec AM. Cette etude observationnelle a identifie le taux de lymphocytes comme etant le principal facteur predictif d’IPCO. Des etudes prospectives sont necessaires pour confirmer ce seuil en prospectif et juger de l’utilite de realiser un scanner thoracique systematique pour ces patients.

Resume Objectifs Pour les patients vivant avec le VIH (PVVIH) naifs, de nombreux schemas d’associations d’antiretroviraux (ARV) peuvent etre utilises et bien souvent ce choix reste subjectif. L’objectif de ce travail est d’evaluer les facteurs associes au choix des molecules en primo-prescriptions d’ARV. Patients et methodes Du 01/01 au 30/10/2014, toutes les primo-prescriptions d’ARV ont ete analysees (donnees patients et donnees prescripteurs), puis reevaluees par un groupe de praticiens « relecteurs ». Resultats Trente-quatre prescripteurs (dans 11 centres) ont inclus 132 patients : 71 H, migrants : 57 %, homosexuels : 21 %, CD4 3 : 26 %, charge virale VIH > 100 000 cp/mL : 33 %. Les schemas prescrits ont ete : INRT/IP (43 %), INRT/INNRT (29,5 %), INRT/anti-integrase (23 %). Le choix etait conforme aux recommandations dans 75 % des cas. Ni les facteurs de risque, ni l’origine des patients, ni le taux de CD4 n’ont influence le choix du 3 e agent. En revanche, ce choix etait influence par l’activite professionnelle ( p = 0,007), un desir de grossesse ( p = 0,07), une grossesse ( p = 0,001), la primo-infection ( p = 0,049) et le niveau de charge virale ( p = 0,02). Ni l’âge, ni l’anciennete dans la prise en charge des PVVIH, ni la taille de la file active de chaque prescripteur n’a influe le choix des ARV. La non-conformite etait principalement le fait de l’utilisation des anti-integrases ( p Conclusions La prescription d’ARV chez les patients naifs respecte globalement les recommandations. Les facteurs influencant les choix sont essentiellement lies a l’existence d’une primo-infection, aux particularites de la procreation, et au niveau de charge virale. Les 25 % de prescriptions non conformes aux recommandations temoignent de l’interet des praticiens pour les classes therapeutiques mieux tolerees.

Introduction Peu de cas de COVID-19 chez des patients infectes par le VIH ont ete rapportes dans la litterature. Nous decrivons les caracteristiques clinicobiologiques et l’evolution de la COVID-19 chez 10 patients infectes par le VIH. Materiels et methodes 10 patients (1,8 %) de notre file active de 560 patients ont eu la COVID-19 entre le 9 mars et le 30 avril 2020. Le diagnostic d’infection a Coronavirus SARS-CoV-2 a ete fait par amplification par PCR en temps reel du gene E du betacoronavirus sur ecouvillon nasopharynge. Resultats Dix patients infectes par le VIH-1, 6 hommes et 4 femmes, d’âge moyen 56 ans ont presente la COVID-19. L’infection par le VIH avait ete diagnostiquee depuis 19 ans environ (min : 6 mois, max : 32 ans). Sept patients sur 10 etaient classes stade C. Tous les patients avaient un traitement antiretroviral : tritherapie (9/10) ou bitherapie (1/10), une charge virale VIH indetectable et des LT CD4 > 200/mm3 (min : 295, max : 1350/mm3). Quatre patients ont ete hospitalises pour une pneumonie, 1 patiente avec antecedent de cancer du poumon a presente une pneumonie nosocomiale a SARS-CoV-2. Quatre patients ambulatoires avaient une infection respiratoire haute et 1 un tableau digestif isole. Les patients hospitalises pour pneumonie communautaire avaient des comorbidites : hypertension arterielle (4/4), diabete de type 2 (4/4), obesite (2/4), maladie respiratoire chronique (1/4). La presentation clinique comprenait : fievre (7/10), toux (7/10), anosmie et agueusie (3 des 5 patients ambulatoires) et troubles digestifs (3/10). La guerison survenait en 7 a 14 jours sous traitement symptomatique (formes ambulatoires). L’hospitalisation survenait entre 7 et 12 jours apres le debut des symptomes avec une duree d’hospitalisation de 8 a plus de 45 jours. Deux patients ont presente un SDRA : une decedee a 12 jours en medecine ; l’autre admis en reanimation avec ventilation mecanique pendant 2 mois. La patiente decedee a eu du ritonavir/lopinavir, une corticotherapie et un antagoniste du recepteur IL1. Les autres patients hospitalises ont recu : antibiotiques (4/5), hydroxychloroquine (2/5), antagoniste du recepteur C5 (1/5). Conclusion Les patients infectes par le VIH ont les memes presentations cliniques que ceux non infectes par le VIH avec des formes severes de COVID-19 survenant chez des patients ayant les facteurs de risque decrits dans la litterature (âge, comorbidites tels l’hypertension arterielle, le diabete, l’obesite ou une pathologie respiratoire chronique). Une infection par le VIH bien controlee sur le plan immunovirologique ne semble pas etre un facteur de risque de COVID-19. Par ailleurs, le traitement antiretroviral en cours ne semble pas etre un facteur protecteur contre l’infection a SARS-CoV-2. Une etude etiologique est necessaire pour confirmer ces hypotheses.

International audience; Objectives - Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis.Methods - We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes.Results - Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified.Conclusions - LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

Background. Calendar trends in virologic failure (VF) among human immunodeficiency virus (HIV)-infected patients can help to evaluate the performance of healthcare systems and the need for new antiretroviral therapy (ART). We examined the time trend in the rate of VF beyond 6 months of ART between 1997 and 2011 in France. Methods. We included patients from the French Hospital Database on HIV who received at least 6 months of ART. VF was defined as 2 consecutive plasma HIV-RNA values >500 copies/mL or as 1 value >500 copies/mL followed byatreatment switch. We adjusted for patients’ characteristics by fitting a multivariable generalized estimating equation logistic regression model with an exchangeable covariance matrix. Results. A total of 81738 patients were enrolled, and median follow-up was 112.4 months. Median CD4 count was 333 cells/µL, and 23% of patients had HIV infection classified as Centers for Disease Control and Prevention stage C. Overall, 29.3% of patients received single/dual-drug ART initially, and 45.4% of patients experienced at least 1 episode of VF during follow-up. The percentage of patients with VF fell from 61.5% in 1997–1998 to 9.7% in 2009–2011 (P

The efficacy and safety of switching to a combined regimen containing darunavir/ritonavir (DRV/r) was investigated in a retrospective study.Sixty-six experienced patients receiving once-daily DRV/r (900/100 mg) in various regimens were included (median age 51 y; male 82%; Centers for Disease Control and Prevention (CDC) stages B or C 70%). The number of patients with plasma HIV RNA50 copies/ml increased from 71% (45/63) at baseline (before switch) to 84% (52/62) at visit 1 (weeks 3-11), and to 92% (60/65) at visit 2 (weeks 12-24). CD4 cells increased from 498 ± 201 cells/mm³ at baseline to 567 ± 232 cells/mm³ by visit 2. Good digestive and metabolic tolerance was observed. The median steady-state DRV plasma concentration, measured 24 ± 4 h after the last drug intake, was 1427 ng/ml. All DRV plasma concentrations were above the protein-binding corrected median effective concentration (EC₅₀) for the wild-type virus (55 ng/ml).Once-daily DRV/r (900/100 mg) was efficacious in pretreated patients, with safe responses.

Objectives The mechanism of raltegravir (RAL)-resistant evolutions has not already been elucidated. Because the emergence of RAL resistance is usually initiated by the N155H mutant, we assessed the role of minor N155H-mutated variants in circulating RNA and archived DNA in five heavily treated patients experiencing long-term RAL therapy failure and harbouring three different resistance profiles determined by standard genotyping. Methods Allele-specific polymerase chain reaction (AS-PCR) was used to detect N155H mutants in longitudinal stored plasma and whole-blood samples before, during and after RAL-based regimens in five patients infected with the HIV-1 B subtype. Results No minor N155H-mutated variant was found by AS-PCR in either plasma or whole-blood samples collected at baseline and after RAL withdrawal in any of the five patients. During RAL failure, the mutation N155H was detected at different levels in three patients displaying the N155H pathway and gradually declined when the double mutant Q148H+G140S was selected in one patient. In two patients with the Q148H resistance pathway, no N155H variant was identified by AS-PCR in either viral RNA or DNA. Conclusions The N155H mutation present at various levels from minority to majority showed no relationship with the three RAL-associated resistance profiles, suggesting that this mutant may not play a role in determining different resistance profiles. Moreover, pre-existing N155H is very infrequent and, if selected during RAL failure, the N155H mutant disappears quickly after RAL withdrawal.

Introduction Du fait de l’augmentation de l’âge des patients et du risque de vieillissement premature, le vieillissement des patients infectes par le VIH (PVVIH) devient une realite de sante publique. Afin d’ameliorer la prise en charge de cette population particuliere, nous avons realise une etude visant a evaluer les comorbidites associees des PVVIH âges de plus de 75 ans. Materiels et methodes Recueil standardise des caracteristiques demographiques, virologiques, immunologiques, therapeutiques des patients du Corevih âges de 75 ans et plus en 2016. Les comorbidites evaluees etaient les suivantes : insuffisance renale (ClCr

Background Darunavir (DRV) is the latest protease inhibitor (PI) to be approved for antiretroviral-naive and -experienced HIV-infected patients. Objectives We examined virologic and immunologic outcomes of highly antiretroviral-experienced patients with triple-class drug resistance receiving DRV/r-based regimens, and attempted to identify factors predictive of virologic success. Study design We studied patients beginning a ritonavir-boosted DRV (DRV/r 600/100 mg twice daily)-containing regimen. Virologic success was defined as plasma viral load (pVL) Results We studied 62 patients with very severe immunodeficiency (CDC stage C in 69% of cases; median CD4 cell nadir 12/mm3). They had previously received a median of four PI and had extensive PI resistance, with a median of three major PI and two DRV resistance mutations. The baseline median pVL and CD4 cell count values were 4.6 log10 and 150/mm3. At week 36, pVL had fallen by 2.6 log10 and the CD4 cell count had risen by 123 cells/mm3. The virologic success rate was 55% overall, and was improved by concomitant first use of enfuvirtide (67%), raltegravir (69%) or etravirine (75%). Virologic success was independently associated with fewer major PI mutations, previous tipranavir exposure, and concomitant first use of enfuvirtide or raltegravir. Conclusions In these highly antiretroviral-experienced patients with triple-class drug resistance, virologic success of DRV-containing regimens was mainly associated with the use of new drug classes and/or fully active drugs. Interestingly, previous tipranavir failure did not undermine the efficacy of DRV, confirming the low level of cross-resistance and, probably, distinct resistance profiles between DRV and tipranavir.

Resume Introduction La lymphogranulomatose venerienne (LGV) est une maladie sexuellement transmissible rare provoquee par Chlamydiae trachomatis serovar L. Depuis 2003–2004, on assiste a une epidemie de rectites liees a la LGV C. trachomatis (serovar L2b) chez des patients homosexuels masculins, en particulier infectes par le VIH, en Amerique du Nord et en Europe, y compris en France. Observation Un homme de 41 ans, infecte par le VIH, presentait depuis trois semaines une volumineuse lesion granulomateuse ulceree de la verge et une adenopathie inguinale sans atteinte rectale associee. Un traitement par doxycycline, 200 mg/j pendant trois semaines, permettait une disparition totale des lesions. La positivite de la recherche par PCR de C. trachomatis (serovar L2) sur les serosites de l’ulceration genitale confirmait le diagnostic de bubonulus genital lie a la LGV. Discussion Depuis le debut de la recente epidemie occidentale de rectites liees a la LGV, les descriptions cliniques de lesions genitales masculines sont rares. Le diagnostic de LGV doit etre systematiquement evoque devant une lesion genitale sexuellement transmise, meme devant un aspect atypique, surtout chez les patients infectes par le VIH.

International audience; EASL International Liver Congress, APR 13-17, 2016, Barcelona, SPAIN

Resume Situation La prevalence de l'infection a VIH (virus d'immunodeficience humaine) augmente en France, l'incidence restant elevee et les multitherapies antiretrovirales reduisant fortement la mortalite. Les personnes infectees par le VIH ont desormais une esperance de vie augmentee et sont susceptibles d'etre pris en charge en reanimation plus facilement. Methode Nous avons realise en France metropolitaine une enquete nationale comparative (82 etablissements de sante) portant sur les pratiques des reanimateurs ( n = 101) et des medecins referents ( n = 78) pour la prise en charge du VIH, afin de connaitre leurs attitudes therapeutiques concernant les antiretroviraux dans differentes situations de reanimation. Resultats Les resultats demontrent une heterogeneite importante dans les reponses des reanimateurs, avec une proportion importante de reponses « non tranchees ». L'attitude des medecins referents pour le VIH semble plus homogene. Il apparait une absence de collaboration entre les deux specialistes au sein des hopitaux. Les CISIH (Centres d'information et de soin de l'immunodeficience humaine) sont peu consultes. Conclusion Il est necessaire de renforcer les connaissances des reanimateurs vis-a-vis d'une pathologie et de traitements en constante evolution. L'acces a l'information actualisee ou a un medecin referent doit etre simplifie et il convient de developper des etudes sur la gestion des antiretroviraux en reanimation.

Resume Objectifs Caracteriser par une methode d’imagerie reproductible les redistributions adipeuses abdominales chez les patients infectes par le virus de l’immunodeficience humaine (VIH) cliniquement lipodystrophiques. Materiels et methodes 89 patients VIH cliniquement lipodystrophiques ont ete inclus dans l’etude. Une seule coupe axiale abdominale ponderee T1 passant par le milieu du corps de la quatrieme vertebre lombaire (L4) est realisee en apnee. Deux radiologues mesurent de facon semi-automatique les surfaces de tissu adipeux abdominales dans les regions sous-cutanees (SAT) et viscerales (VAT). Les mesures sont comparees a celles de temoins apparies (ethnie, sexe, âge et indice de masse corporelle). Resultats Les mesures de surfaces adipeuses abdominales en IRM sont reproductibles. Chez l’homme lipodystrophique : on decrit trois formes cliniques de lipodystrophie avec augmentation du tissu adipeux visceral (VAT) et diminution du tissu graisseux sous cutane (SAT) par rapport aux sujets sains. Chez les femmes, on retrouve deux formes cliniques de lipodystrophie avec une augmentation du VAT mais aucune diminution du SAT. Conclusion L’IRM avec comparaison malades-temoins apparies est une methode reproductible pour caracteriser les redistributions adipeuses de la lipodystrophie et en evaluer la severite. Un large referentiel IRM de distribution du tissu adipeux abdominal sur temoins serait utile a l’etude des pathologies metaboliques.

29-69 % of pneumonias are microbiologically documented because it can be considered as an invasive procedure with variable test sensitivity. However, it drastically impacts therapeutic strategy in particular the use of antibiotics. Serum protein electrophoresis (SPEP) is a routine and non-invasive test commonly used to identify serum protein disorders. As virus and bacteria may induce different globulins production, we hypothesize that SPEP can be used as an etiological diagnosis test. Retrospective study conducted from 1/1/13 until 5/1/15 among patient hospitalized for an acute community-acquired pneumonia based on fever, crackles and radiological abnormalities. α/β, α/γ, β/γ globulins and albumin/globulin (A/G) ratio were calculated from SPEP. Data were analyzed in 3 groups: documented viral (DVP) or bacterial pneumonia (DBP) and supposedly bacterial pneumonia (SBP). We used ANOVA statistic test with multiple comparisons using CI95 and ROC curve to compare them. 109 patients included divided into DBP (n = 16), DVP (n = 26) and SBP (n = 67). Mean age was 62 ± 18 year-old with a sex ratio M/F of 1.3. Underlying conditions (e.g. COPD, diabetes) were comparable between groups in multivariate analysis. Means of A/G ratio were 0.80 [0.76-0.84], 0.96 [0.91-1.01], 1.08 [0.99-1.16] respectively for DBP, SBP and DVP (p = 0.0002). A/G ratio cut-off value of 0.845 has a sensitivity of 87.5 % and a specificity of 73.1 %. A/G ratio seems to be an easy diagnostic tool to differentiate bacterial from viral pneumonia. A/G ratio cut-off value below 0.845 seems to be predictable of a bacterial origin and support the use of antibiotics.

International audience; Background - Chronic kidney disease (CKD) is frequent in individuals infected with human immunodeficiency virus (HIV). Progression to end-stage renal disease can be slowed by appropriate medical management. Methods - To assess whether active promotion of guidelines improves CKD management, we conducted a cluster randomized controlled trial within the French Hospital Database on HIV (FHDH-ANRS CO4). We randomized 46 centers participating in the FHDH to either simple information on guideline availability or active promotion with a multifaceted and repeated intervention comprising reminders and audit feedback and targeting of local opinion leaders carried out between April 2009 and April 2010. Outcome measure was CKD management adequacy assessed before and 2 years after the beginning of the intervention in HIV-infected patients with moderate to severe CKD. CKD management was considered adequate in case of referral to a nephrologist or if proteinuria, blood pressure, low-density lipoprotein cholesterol level, and glycemia had been measured during the previous year and medications had been prescribed when necessary. Results - Three hundred six patients were enrolled, of whom 238 (78%) completed the 2 years of follow-up. During the study period, the percentage of patients receiving adequate CKD management improved from 64.1% to 70.4% (+6.3%) in the active arm and from 68.3% to 75.6% (+7.3%) in the control arm (adjusted mean difference, -0.7 percentage points [95% confidence interval: -9.2 to 7.9]; P = .95). The biggest impact of active promotion was on the management of proteinuria and blood pressure. Conclusions - Adequate compliance with CKD management guidelines improved slightly between 2009 and 2011, with no difference between the simple information and active promotion arms. Clinical trials registration - CCTIRS 10.150 and CNIL DR-2010-379.

Background Thirteen clustered cases of American histoplasmosis, a deep mycosis caused by Histoplasma capsulatum and acquired through inhalation of airborne spores was reported. Twenty-five persons traveled in Martinique, French West Indies. Thirteen underwent trekking and passed through a mountain tunnel full of bats (tunnel group). The 12 others performed canyoning and did not go through the tunnel (control group). Fifteen days after exposure, 1 patient of the tunnel group developed fever, chills, and cough. Methods The index case was diagnosed in the hospital, but 12 cases where initially diagnosed as prolonged influenza. All individuals were contacted and submitted to a phone questionnaire. They were asked about eventual occurrence of influenzalike symptoms, about activities practiced, and the notion of contact with bats. All were invited to have clinical examinations, chest x-ray films, and blood samplings. Serologic testing for histoplasmosis was performed by immunodiffusion. Clinical evidence of infection with H. capsulatum was obtained in all the remaining patients of the tunnel group and in none in the control group. Symptoms occurred with an acute onset in 11 to 23 days: fever and chills, severe asthenia, headaches, digestive tract involvement, and then cough, dyspnea, hepatic involvement. Pulmonary micro- or macronodules and mediastinal adenopathies were seen on radiograph and/or computed tomography scan. ResultsH. capsulatum serologic tests were positive in all 13 cases with presence of specific M and or H precipitins, 5 to 13 weeks after exposure, and were negative in control group. All patients were treated with itraconazole 200 mg per day during at least 2 months. Treatment was well tolerated; patients progressively recovered. Clinical and serologic follow-up was obtained for some patients at 1 and 4 years. The present study reports the first large outbreak of histoplasmosis acquired in Martinique. Conclusion Histoplasmosis still occurs and is potentially serious. In patients returning from endemic areas, presenting prolonged influenzalike symptoms, clinicians should look for previous possible exposure to Histoplasma.

Treating Hepatitis C among HIV patients under antiretroviral drug therapy requires a high degree of vigilance and continuous monitoring because of frequent problems with intolerance and/or drug interactions. Recent studies, including three therapeutic trials, on Ribavic, APRICOT, and ACTG A5671, have given some insights on following these patients up. The adverse effects are relatively similar in HCV-HIV-co-infected patients and patients infected by HCV only. Their frequency is, on the other hand, higher among HCV-HIV-Co-infected patients. The adverse-effects are consistent, in a non-exhaustive way, with pseudo influenza-like symptoms, fever, myalgia, cephalgia, with psychiatric disorders (irritability, depression, etc.); endocrine disorders (thyroid dysfunction, diabetes...); and with hematological anomalies especially anemia and leucopenia. But the percentage of lymphocyte T CD4 is not modified, therefore there is no risk of opportunistic infection. Pharmacokinetic interactions between antiretroviral drugs and treatment for HCV infection including ribavirin plus interferon alpha (IFN-alpha) or pegylated IFN are described. They are almost exclusively due to the combination of ribavirin and of nucleoside analogue reverse transcriptase inhibitors. One of the principal consequences is the emergence of mitochondrial toxicity defined by the occurrence of hyperlactatemia, or acute pancreatitis). Thus, some combinations should be avoided such as ddI+ribavirin and ddI+d4T+ribavirin. The d4T+ribavirin combination must also be used with caution.

Background We have previously shown that lipid alterations in HIV-1-associated lipodystrophy (LD) are correlated with decreased serum dehydroepiandosterone (DHEA) and increased cortisol:DHEA ratio and IFN-α levels. Objective To evaluate in a longitudinal study whether steroid and cytokine modifications are associated with the evolution of physical changes and lipid alterations associated with LD. Methods Thirty-four HIV-1-positive men were followed during 32·5 ± 4·0 months and tested at four time-points. The patients were subdivided into five groups according to physical changes and anthropometric measurements: LD-negative, initially LD-negative becoming LD-positive, LD-positive unchanged, aggravated or improved. Serum lipids, apolipoproteins, adrenal steroids and cytokines were measured and compared with baseline values. Results (1) LD aggravation is associated with persistent elevated lipids, a decrease in serum DHEA, an increase in cortisol:DHEA ratio and persistent high levels of IFN-α. (2) LD improvement is associated with normalization of serum lipids, an increase in serum DHEA leading to normalization in cortisol:DHEA ratio, and normalization of IFN-α levels. (3) In LD-positive men evolution of VLDL cholesterol is negatively correlated with DHEA (r = −0·56, P

Gonococcal arthritis is typically acute and appears within 3 weeks after initial infection. Chronic gonococcal arthritis is now exceptionally rare, since the advent of the antibiotic era. Numerous host factors are involved in gonococcal dissemination, such as complement deficiency, HIV and gonococcus strain characteristics. Gonococcal arthritis shares the same risk factors. In this instance, our patient was a 16-year-old girl suffering from persistent polyarthralgia with joint swelling presenting with brief flare-ups for a period of 1 year. She disclosed a single episode of unprotected sexual intercourse 1 year ago, i.e. just before developing her first rheumatological symptoms. Therefore, we performed a joint aspiration (arthrocentesis), and synovial fluid was inoculated directly into aerobic and anaerobic blood culture bottles, which tested positive for Neisseria gonorrhoeae within 24 h. Clinical presentation was consistent with previous reports of chronic gonococcal arthritis. Further investigation revealed a C5 complement deficiency, which might explain the chronic Neisseria process. A favourable outcome was reached after a ten-day course of IV ceftriaxone, with no apparent sequelae found during follow-up 6 weeks later. This case demonstrates an unusual gonococcal arthritis with brief flare-ups for the course of a year, followed by a subacute form. N. meningitidis infections, similar to N. gonorrhoeae, are typically acute and may sometimes be involved in chronic processes. However, this characteristic appears to be rare in the case of N. gonorrhoeae. Risk factors for this chronic process will be discussed with a review of the literature.

Objective To assess the efficacy of highly active antiretroviral treatment (HAART) on AIDS-Kaposi's sarcoma (KS). Design Prospective cohort of patients followed for 24 months. Setting Four referral hospitals of the West Paris metropolitan area. Patients/intervention Thirty-nine AIDS-KS patients, 42 +/- 9 years old, who began HAART (HIV-protease inhibitor and two nucleoside analogues) between March and December 1996, were enrolled. One was lost to follow-up at month 12. Main outcome measures KS response, using criteria of the AIDS clinical trials group (ACTG), CD4 cell counts, and plasma HIV-RNA, assessed every 6 months. ACTG TIS staging of KS. Results Eighteen patients had T1 KS and 21 T0 KS. One patient died from KS at month 6. KS improved progressively, with complete and partial response rates of 46% and 28% at month 24, respectively. Only six patients were still receiving systemic KS therapy at month 24. Complete response was observed in 10 of the 19 patients without systemic KS therapy at inclusion. Patients with complete response at month 24 had higher CD4 cell counts than others (465 +/- 343 versus 185 +/- 167 x 10(6)/l; P 150 x 10(6)/l [odds ratio (OR), 13.4; 95% confidence interval (CI), 2-82] and T0 KS at inclusion: [OR, 7; 95% CI, 1.1-42] were predictive of complete response at month 24. Conclusions HAART appears to have prolonged efficacy on AIDS-KS, even without specific KS therapy, and this effect appears to be linked to the restoration of immune function.

Background: A syndrome of lipodystrophy, associated with hypertriglyceridaemia, hypercholesterolaemia, hyperinsulinaemia and peripheral insulin resistance has been reported in protease inhibitor (PI)-treated HIV-infected patients. Because lipid metabolism, fat mass distribution and insulin resistance are partly regulated by steroid hormones, we questioned whether lipodystrophy is related to hormonal perturbations. Objective: To evaluate serum lipid and steroid hormone concentrations in HIV-positive men on highly active antiretroviral therapy (HAART) in order to determine whether dyslipidaemia, peripheral loss of fatty tissue and central fat accumulation are related to steroid hormone modifications. Design: A cross-sectional study. Methods: Thirty-seven HIV-1-positive men on HAART, 23 of whom had symptoms of lipodystrophy, according to a subjective clinical score of lipodystrophy (SCSL), were tested. Serum concentrations of cholesterol, triglycerides and their subclasses, apolipoproteins and steroid hormones, including cortisol, dehydroepiandrosterone (DHEA), DHEA sulphate, androstenedione, testosterone and dihydrotestosterone were measured. Results: Serum cholesterol, very low density lipoprotein (VLDL) cholesterol, triglycerides, VLDL triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL) triglycerides, apolipoprotein B (ApoB) and atherogenic ratios of cholesterol:HDL cholesterol, LDL cholesterol:HDL cholesterol and ApoB:apolipoprotein A1 (ApoA1) were significantly increased in lipodystrophy-positive compared with lipodystrophy-negative men. The serum cortisol level was similar in lipodystrophy-positive versus lipodystrophy-negative men, but was elevated compared with controls. Serum DHEA was significantly lower in lipodystrophy-positive versus lipodystrophy-negative men and, consequently, the cortisol:DHEA ratio was increased in lipodystrophy-positive patients. A positive correlation was found between the cortisol:DHEA ratio and increased levels of atherogenic lipids. In addition, the SCSL was positively correlated with dyslipidaemia and the cortisol:DHEA ratio. Conclusion: This study demonstrates an association between the cortisol:DHEA ratio, lipid alterations and lipodystrophy. This syndrome might result from an imbalance between peripheral lipolysis and lipogenesis, both regulated by cortisol and DHEA.

Twenty-four cerebrospinal fluid (CSF) samples from 19 AIDS patients with neurological signs were analysed by the polymerase chain reaction (PCR) for the presence of JC virus (JCV). Eleven of the 19 patients tested presented with progressive multifocal leucoencephalopathy (PML). Two specific JCV target sequences were used for the PCR analysis: a sequence specific for the T antigen genes from both BK virus (BKV) and JCV (PCR1) and a sequence specific for the large T antigen gene from JCV (PCR2). The JCV genome was detected in 10 of 11 patients with PML by the PCR1 method and in all 11 patients by the PCR2 method. With samples from the eight patients without PML, one positive result was obtained with the PCR1 method and this sample and another gave positive results with PCR2. Multiple CSF samples were collected from three patients with PML at different times, including after intrathecal cytarabine treatment, and were tested by the PCR2 method for the presence of the JCV genome. The PCR result became negative for two of the three patients during the cytarabine treatment. However, the absence of a PCR signal was not associated with clinical improvement in these patients. The PCR method is useful for the detection of JCV in CSF samples and in the diagnosis of PML. However, the application of PCR for monitoring the effect of treatment remains to be established.

International audience; OBJECTIVES: The aims of the study were to assess in patients with advanced HIV disease receiving antiretroviral therapy (ART) intensification with enfuvirtide (i) resistance at virological failure (VF), (ii) impact of baseline tropism on immunovirological response, and (iii) HIV-1 DNA tropism evolution during ART. METHODS: The ANRS 130 APOLLO randomized trial evaluated in naive patients the immunovirological impact of standard ART without (control arm) or with enfuvirtide. Tropism was determined on RNA and DNA by V3-loop sequencing interpreted using the Geno2Pheno algorithm. RESULTS: At baseline the median CD4 cell count was 30 cells/mm(3). Among the 170 patients assessable in this virological substudy, HIV-1 RNA tropism was as follows: 60% of viruses were R5 and 40% were R5X4/X4. HIV-1 DNA tropism was as follows: 54% were R5 and 46% were R5X4/X4. At week 24, 39% and 49% of patients experienced VF in the enfuvirtide and control arms, respectively. In the enfuvirtide arm, only resistance-associated mutations to enfuvirtide were detected. In the control arm, two patients displayed drug-resistant viruses at the time of VF. No impact of baseline tropism was observed on immunovirological response, regardless of the study arm. Among the 25 patients experiencing DNA tropism switch between baseline and week 24, 16 (64%) switched from R5 to R5X4/X4. These latter were mostly successfully suppressed patients receiving enfuvirtide and exhibiting poorer immunological response. CONCLUSIONS: Baseline RNA tropism had no impact on the immunovirological response. Drug resistance mutations were only detected for the fusion inhibitor. Finally, the mechanism of replenishment of the viral cellular reservoir with X4 viruses observed needs to be further analysed.

The recent augmentation of the prevalence of multidrug resistant (MDR) tuberculosis is related to the high incidence of tuberculosis in HIV infected people, especially in those with low social status and no medical care; several nosocomial epidemics of MDR tuberculosis were observed in American and European institutions where HIV-infected persons were hospitalized; these MDR tuberculosis were associated with a high mortality-rate and frequent nosocomial transmission to immunocompromised contacts and care workers. The rapid institution of an adequate treatment with ancient antituberculosis agents (cycloserin, capreomycin, aminoglycosides) and/or new drugs (rifabutine, ofloxacin, sparfloxacin, etc) is necessary to avoid mortality and to diminish transmission. Prevention of MDR tuberculosis transmission is very important: patient isolation, adequate and prolonged therapy, better detection of resistance with gene-amplification methods (PCR) which are under investigation.

The mechanism of raltegravir (RAL)-resistant evolutions has not already been elucidated. Because the emergence of RAL resistance is usually initiated by the N155H mutant, we assessed the role of minor N155H-mutated variants in circulating RNA and archived DNA in five heavily treated patients experiencing long-term RAL therapy failure and harbouring three different resistance profiles determined by standard genotyping.Allele-specific polymerase chain reaction (AS-PCR) was used to detect N155H mutants in longitudinal stored plasma and whole-blood samples before, during and after RAL-based regimens in five patients infected with the HIV-1 B subtype.No minor N155H-mutated variant was found by AS-PCR in either plasma or whole-blood samples collected at baseline and after RAL withdrawal in any of the five patients. During RAL failure, the mutation N155H was detected at different levels in three patients displaying the N155H pathway and gradually declined when the double mutant Q148H+G140S was selected in one patient. In two patients with the Q148H resistance pathway, no N155H variant was identified by AS-PCR in either viral RNA or DNA.The N155H mutation present at various levels from minority to majority showed no relationship with the three RAL-associated resistance profiles, suggesting that this mutant may not play a role in determining different resistance profiles. Moreover, pre-existing N155H is very infrequent and, if selected during RAL failure, the N155H mutant disappears quickly after RAL withdrawal.

International audience; OBJECTIVES: To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. METHODS: From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan-Meier curves and Cox models. RESULTS: The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05-3.79). CONCLUSIONS: Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided.

Ten severely immunocompromised HIV–HCV co-infected patients were enrolled in a quantifiable HCV-RNA assay. Serum alanine aminotransferase, HCV-RNA levels and HIV viral loads were determined at baseline, at month three and at month six after initiation of a highly active antiretroviral therapy including an HIV protease inhibitor. HCV genotypes were determined using a line probe assay kit. Our results suggested that this therapy did not result in lower HCV viraemia, whatever the HCV genotypes, and probably had no effect on the outcome of chronic viral hepatitis C. As our patients were severely immunocompromised and their mean increase of CD4 cell counts was less than 50/mm 3 , we cannot reach any conclusions about the impact of the improvement of immune status on the HCV-RNA load.

Background: The effect of syphilis on HIV infection remains controversial. Most studies involved small sample sized population and did not account for cART effects on HIV markers. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P223 Cite this article as: Jarzebowski et al.: Syphilis infection is associated with an increase in plasma viral load in HIV infected patients: results from the FHDH cohort — ANRS CO4. Journal of the International AIDS Society 2010 13(Suppl 4):P223. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113009/

Resume L'objectif de cette etude ouverte prospective etait d'evaluer l'interet des aerosols d'isethionate de pentamidine a la dose quotidienne de 300 mg dans le traitement de relais de 13 episodes de pneumocystose survenus chez des patients atteints de syndrome d'immunodeficience acquise. Les aerosols de pentamidine ont ete administres dans 11 cas apres un traitement d'une duree moyenne de 10 jours par l'association trimethoprime-sulfamethoxazole, et dans 2 cas apres 6 jours de traitement par la pentamidine intraveineuse. Apres une duree totale du traitement anti-Pneumocystis de 21 jours, tous les patients ont ete consideres gueris sur les criteres cliniques. Une aggravation des anomalies radiologiques et gazometriques a ete constatee chez deux patients presentant une pathologie pulmonaire associee (tuberculose et sarcome de Kaposi). La tolerance des aerosols de pentamidine a ete bonne. Deux patients ont developpe des signes de surinfection bronchique. Au total, cette etude montre l'interet du traitement sequentiel — traitement par voie generale puis locale — des pneumocystoses non severes liees au SIDA.

Solid organ transplantations (SOT) are performed successfully in selected HIV-infected patients. However, multiple and reciprocal drug–drug interactions are observed between antiretroviral (ARV) drugs and calcineurin inhibitors (CNIs) through CYP450 metabolization. Raltegravir (RAL), a novel HIV-1 integrase inhibitor, is not a substrate of CYP450 enzymes. We retrospectively reviewed the outcomes of 13 HIV-infected transplant patients treated by an RAL + two nucleosidic reverse transcriptase inhibitor (NRTI) regimen, in terms of tolerability, ARV efficacy (plasma viral load, CD4 cell count), drug interactions, RAL pharmacokinetics and transplant outcome. Thirteen patients with liver (n = 8) or kidney (n = 5) transplantation were included. RAL was initiated (400 mg BID) either at time of transplantation (n = 6), or after transplantation (n = 7). Median RAL trough concentration was 507 ng/mL (176–890), which is above the in vitro IC95 for wild type HIV-1 strains (15 ng/mL). Target trough levels of CNIs were promptly obtained with standard dosages of tacrolimus or cyclosporine. RAL tolerability was excellent. There was no episode of acute rejection. HIV infection remained controlled. After a median follow-up of 9 months (range: 6–14), all patients were alive with satisfactory graft function. The use of an RAL + two NRTI-based regimen is a good alternative in HIV-infected patients undergoing SOT.

Lymphogranuloma venereum (LGV) is an uncommon sexually transmitted disease caused by the L serovars of Chlamydiae trachomatis. Since 2003-2004, a continued outbreak of LGV proctitis (C. trachomatis serovar L2b) has been reported in North America and Europe, including France, among homosexual males, especially with HIV co-infection.A 41-year-old man presented penile ulceration of three weeks' standing, associated with a large swollen granulomatous lesion and an inguinal lymph node but without proctitis. All lesions resolved after a three-week course of doxycycline 200mg daily. These lesions were related to a genital bubo due to LGV as confirmed by positive specific PCR for C. trachomatis (serovar L2) performed on the genital ulceration.Clinical descriptions of male genital LGV are infrequent, even during the LGV proctitis epidemic seen in Western countries in recent years. A diagnosis of LGV must be considered in the presence of sexually transmitted genital lesions, even atypical, especially among HIV-infected patients.

To characterize intra-abdominal adipose tissue changes in HIV patients with clinical lipodystrophy using a reproducible imaging technique. Materials and methods. 89 HIV patients with clinical lipodystrophy were included. A single axial T1W image was acquired at the mid L4 vertebral level. Two radiologists measured subcutaneous (SAT) and visceral (VAT) adipose tissues using a semi-automated method. Measurements were compared to a matched population (race, sex, age and BMI).Measurements of abdominal adipose tissue on MRI are reproducible. Three clinical types of lipodystrophy are described in males with increased visceral (VAT) and reduced subcutaneous (SAT) adipose tissues compared to control subjects. Two clinical types of lipodystrophy are described in females with increased visceral (VAT) and unchanged subcutaneous (SAT) adipose tissues.MRI with comparison between HIV patients and normal control subjects is a reproducible method to characterize adipose tissue changes of lipodystrophy and evaluate its severity. Evaluation of a adipose tissue distribution in a large control population would be helpful to the study of metabolic disorders.

The HIV-positive population is still increasing because the incidence of the disease remains high while the effectiveness of highly active antiretroviral therapy (HAART) has dramatically reduced mortality. HIV infected patients have an increased life expectancy and are more readily admitted to intensive care units.We conducted a nation-wide comparative study in France of how these patients are managed by ICU specialists, on one hand, and HIV specialists, on the other, to better understand the use of antiretroviral therapy in critically ill patients.The results show heterogeneous responses of ICU specialists with an important proportion of non decisive answers. The answers of HIV specialists are more homogeneous. There appears to be little or no cooperation between the two specialties. The CISIH (French centers for the information and care of human immunodeficiency) are rarely consulted.ICU specialists must be better informed on this rapidly evolving disease. Access to updated information or to an HIV specialists must be made easier. Studies should also be made on how HAART is employed in ICUs (pharmacology, pharmacodynamics...).

When boosted by ritonavir, protease inhibitors trough concentration and inhibitory quotient are increased, thus enhancing their therapeutic margin. Although the inhibitory quotient is less high when patients are pre-treated and have developed resistance mutations, it nonetheless offers a precious alternative for patients experiencing therapeutic failure. Despite great inter-individual variability in virologic responses, boosted protease inhibitors can be compared to boosted lopinavir. The latter seems superior to saquinavir boosted and indinavir boosted in terms of virologic efficacy and resistance mutations selection. A conclusion regarding boosted atazanavir and boosted fos-amprenavir versus lopinavir cannot be absolutely drawn on the basis of present results.

Treating Hepatitis C among HIV patients under antiretroviral drug therapy requires a high degree of vigilance and continuous monitoring because of frequent problems with intolerance and/or drug interactions. Recent studies, including three therapeutic trials, on Ribavic, APRICOT, and ACTG A5671, have given some insights on following these patients up. The adverse effects are relatively similar in HCV-HIV-co-infected patients and patients infected by HCV only. Their frequency is, on the other hand, higher among HCV-HIV-Co-infected patients. The adverse-effects are consistent, in a non-exhaustive way, with pseudo influenza-like symptoms, fever, myalgia, cephalgia, with psychiatric disorders (irritability, depression, etc.); endocrine disorders (thyroid dysfunction, diabetes...); and with hematological anomalies especially anemia and leucopenia. But the percentage of lymphocyte T CD4 is not modified, therefore there is no risk of opportunistic infection. Pharmacokinetic interactions between antiretroviral drugs and treatment for HCV infection including ribavirin plus interferon alpha (IFN-alpha) or pegylated IFN are described. They are almost exclusively due to the combination of ribavirin and of nucleoside analogue reverse transcriptase inhibitors. One of the principal consequences is the emergence of mitochondrial toxicity defined by the occurrence of hyperlactatemia, or acute pancreatitis). Thus, some combinations should be avoided such as ddI+ribavirin and ddI+d4T+ribavirin. The d4T+ribavirin combination must also be used with caution.

We have previously shown that lipid alterations in HIV-1-associated lipodystrophy (LD) are correlated with decreased serum dehydroepiandosterone (DHEA) and increased cortisol:DHEA ratio and IFN-alpha levels.To evaluate in a longitudinal study whether steroid and cytokine modifications are associated with the evolution of physical changes and lipid alterations associated with LD.Thirty-four HIV-1-positive men were followed during 32.5 +/- 4.0 months and tested at four time-points. The patients were subdivided into five groups according to physical changes and anthropometric measurements: LD-negative, initially LD-negative becoming LD-positive, LD-positive unchanged, aggravated or improved. Serum lipids, apolipoproteins, adrenal steroids and cytokines were measured and compared with baseline values.(1) LD aggravation is associated with persistent elevated lipids, a decrease in serum DHEA, an increase in cortisol:DHEA ratio and persistent high levels of IFN-alpha. (2) LD improvement is associated with normalization of serum lipids, an increase in serum DHEA leading to normalization in cortisol:DHEA ratio, and normalization of IFN-alpha levels. (3) In LD-positive men evolution of VLDL cholesterol is negatively correlated with DHEA (r = -0.56, P0.01) and positively with cortisol:DHEA ratio (r = 0.62, P0.004) and with IFN-alpha (r = 0.57, P0.01). (4) The switch to LD is associated with a decrease in serum DHEA. (5) Patients who remained LD-negative maintained normal lipids, elevated cortisol and DHEA, and normal cortisol:DHEA ratio and normal levels of IFN-alpha.This study indicates that cortisol:DHEA ratio and serum IFN-alpha levels are closely associated with clinical evolution and atherogenic lipid alterations in LD.

Introduction – objectifs L’adaptation posologique du TDF n’est pas recommandee en cas d’atteinte renale mineure et/ou d’elevation de la concentration residuelle plasmatique de TDF (CresTDF). Nous etudions l’evolution virologique, pharmacologique et renale chez des pts recevant TDF a dose reduite (TDF 300 mg1j/2). Materiels et methodes Etude retrospective de tous les pts infectes par le VIH traites par TDF1j/2 pour atteinte renale moderee et/ou CresTDF eleve. L’efficacite du traitement ARV, les parametres renaux et la CresTDF etaient evalues a M-2, J0, M2, M6, M12 ; donnees en medianes (IQR). Resultats 56 pts, 49♂, 54 (35–80) ans, 43 % stade CDC-C, 32 (12–53) mois de pre-exposition TDF 300 mg/j, ont ete inclus. Les traitements ARV associes comprenaient FTC (n = 50), abacavir (n = 3), INNTI (nevirapine : 3, efavirenz : 9, etravirine : 5), IP boostee (atazanavir : 11, lopinavir : 10, darunavir : 11), et/ou raltegravir (12). Les facteurs de risque etaient HTA (8 pts), diabete (6), tabagisme (26), arteriopathie (12), BMI > 25 (12), dyslipidemie (26), VHC chronique (8) ; 6 pts etaient coinfectes VHB. A J0, creatininemie Cr = 97 μM/l [87–107], clairance de la Cr (CrCl) = 75 ml/mn [64–85] (MDRD) et 72 ml/mn [62–84] (Cockroft-Gault-CG), CresTDF = 135 ng/ml [98–205]. Sous TDF1j/2 : Cr = 92 μM/l [81–101] (p = 0,04), ClCr = 83 ml/mn (70–92) (MDRD) (p = 0,002) et 79 ml/mn [65–91] (CG) (p = 0,004), CresTDF = 91ng/ml [52–124] a 12–24 h (p = 0,002) et 46 ng/ml [32–68] a 36–48 h (p Conclusion La reduction de posologie du TDF a permis de maintenir le TDF dans une combinaison ARV efficace, en reduisant la toxicite renale chez les patients ayant une insuffisance renale legere.

Ritonavir (RTV) is a powerful inhibitor of P450 3A4 cytochorme. When given in combination with indinavir (IDV) it increases the IDV trough concentrations (Cmin) allowing a lower IDV dosage in a twice a day regimen, independently of meals. We report tolerance data and IDV Cmin levels observed in plasma and cerebrospinal fluid (CSF) in a cohort of HIV-infected patients treated with the IDV-RTV combination at different dosages of IDV and RTV.IDV Cmin was assayed 56 times in 40 patients (few patients had received different dosages of the IDV-RTV combination). Tolerance was recorded.For patients given the IDV-RTV combination at the doses of 800/100 mg b.i.d., 800/200 mg b.i.d. or 400/400 mg b.i.d., the IDV Cmin was 12 times the median IDV IC95. If the Cmin/IC95 ratio was greater than 10 with the 800/100 mg b.i.d. regimen and virological success was achieved, the IDV dosage was reduced to 400 mg b.i.d. For these patients, the 400/100 mg b.i.d. IDV-RTV regimen always gave a Cmin above the IDV IC95. Median Cmin for IDV in CSF was 146 ng/ml (range 71-881 ng/ml), above the IDV IC95. It was possible to control most of the adverse effects by reducing dosage after obtaining the IDV pharmacological levels. Definitive interruption of treatment was required in only 2 cases at mean follow-up of 7.9 months.The IDV-RTV combination should be used to improve observance of antiretroviral treatments and reduce the risk of virological failure related to low plasma levels. The IDV-RTV combination at 800/100 mg b.i.d. is a useful protocol when IDV efficacy alone is the goal. The 400/400 mg b.i.d. IDV-RTV regimen is an interesting alternative when efficacy of both inhibitors is the goal. Drug assays should be systematic to adapt individual dosages and limit the risk of adverse effects.

The August 1997 Directive of the Direction of General Health in France extended indications for antiretroviral treatment to risk of HIV exposure by sexual intercourse or syringe sharing. In November 1997, in collaboration with the Hauts-de-Seine MedicoJudiciary center, the Infectious Disease unit of the Raymond Poincaré Garches Hospital established a health care and anti-HIV prophylaxis clinic for victims of sexual assault. We report here the experience in 1998 and 1999.Between January 1998 and December 1999, 109 victims of sexual assault, 105 women and 4 men, mean age 24.7 +/- 10.6 years attended the clinic.Mean delay from assault to antiretroviral tritherapy (AZT, 3TC, indinavir) was 18.35 +/- 17.39 hours. Mean duration of antiretroviral treatment was 17.4 +/- 11.8 days. HIV screening in perpetrators enabled early interruption of the antiretroviral treatment in 23 cases (21.1%). Sixty-two victims (62%) were still in follow-up at W4/W7. Excellent compliance to tritherapy was observed in these subjects. Clinical intolerance was observed in 46.6% with nausea-vomiting in 91.4% of the cases. Adverse effects led to interruption of indinavir in 5 cases. Initial HIV serology was negative in all cases and no case of HIV seroconversion was observed. Among the 23 known perpetrators, one was HIV-positive with an HIV-RNA at 88,000 copies. Sixty-one victims (55.9%) had been previously vaccinated against the hepatitis B virus; 16 victims were vaccinated after the assault. There were no cases of hepatitis B virus seroconversion. Search for chlamydiae in vaginal secretions was positive in 3 cases and chlamydia serology demonstrated a seroconversion in 1 case. There was no case of syphylitic seroconversion and no case of gonococcal or trichomonas infection.The low rate of attendance for follow-up in regards to the gravity of the potential risk of HIV and/or hepatitis B virus transmission and the burden and cost of the antiretroviral treatment highlight the need for better medico-psycho-social support for rape victims. For the victims who attended the clinic, antiretroviral treatment was generally well accepted and well tolerated.