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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.

We report a case of CMV retinitis cured in an AIDS patient after two months of regular HAART therapy without CMV medications.A 37-year-old patient (baseline CD4 count 47/ml) receiving HAART (2 NRTI and 1 IP) showed poor compliance and had increased his CD4 count for two months reaching 263/ml although HIV viral load remained high (71,840 copies/ml). His fundus was normal. He was evaluated 8 months after a period of loss to follow-up: his CD4 count was 65/ml, HIV viral load was 123,000 copies/ml, CMV serology for IgV and viruria were positive, viremia was negative, his fundus revealed a healed CMV retinitis. Six months later and without any CMV therapy, no relapse has been observed while regularly taking HAART medications.Few cases have been reported in which HAART therapy with good immune response and reduced HIV viral load lead to complete regression of CMV retinitis without specific CMV medication. This case suggests that, even with an uncontrolled HIV viral load, HAART via transient immune restoration may contribute to resolving CMV retinitis.

To assess the efficacy of highly active antiretroviral treatment (HAART) on AIDS-Kaposi's sarcoma (KS).Prospective cohort of patients followed for 24 months.Four referral hospitals of the West Paris metropolitan area.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.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.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; P0.01), but the proportion of patients with HIV-1 RNA500 copies/ml was not significantly different. An increase in CD4 cell counts from inclusion to month 12 of150 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.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.

Highly-active antiretroviral therapy (HAART) has lead to a dramatic decrease in the morbidity of patients infected with the human immunodeficiency virus (HIV). However, metabolic side effects, including lipodystrophy-associated (LD-associated) dyslipidemia, have been reported in patients treated with antiretroviral therapy. This study was designed to determine whether successful HAART was responsible for a dysregulation in the homeostasis of tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in lipid metabolism. Cytokine production was assessed at the single cell level by flow cytometry after a short-term stimulation of peripheral blood T cells from HIV-infected (HIV(+)) patients who were followed during 18 months of HAART. A dramatic polarization to TNF-alpha synthesis of both CD4 and CD8 T cells was observed in all patients. Because it was previously shown that TNF-alpha synthesis by T cells was highly controlled by apoptosis, concomitant synthesis of TNF-alpha and priming for apoptosis were also analyzed. The accumulation of T cells primed for TNF-alpha synthesis is related to their escape from activation-induced apoptosis, partly due to the cosynthesis of interleukin-2 (IL-2) and TNF-alpha. Interestingly, we observed that LD is associated with a more dramatic TNF-alpha dysregulation, and positive correlations were found between the absolute number of TNF-alpha CD8 T-cell precursors and lipid parameters usually altered in LD including cholesterol, triglycerides, and the atherogenic ratio apolipoprotein B (apoB)/apoA1. Observations from the study indicate that HAART dysregulates homeostasis of TNF-alpha synthesis and suggest that this proinflammatory response induced by efficient antiretroviral therapy is a risk factor of LD development in HIV(+) patients.

Introduction et but de l’etude L’existence de perturbations des tests hepatiques au cours de l’anorexie mentale est decrite dans la litterature depuis plusieurs annees. Nous avons souhaite analyser les anomalies du bilan hepatique au cours des denutritions graves chez des patients atteints d’anorexie mentale, et observer leur evolution au cours de la renutrition enterale Materiel et methodes Etude retrospective monocentrique de la biologie hepatique chez des patients atteints d’anorexie mentale severement denutris (37 dossiers selectionnes au hasard parmi un collectif de 204 pris en charge entre Janvier 1998 et Octobre 2006). Criteres d’exclusion : affection hepatique, prise de medicaments hepatotoxiques ou d’alcool pouvant expliquer la perturbation du bilan hepatique. Resultats Parmi les patients inclus, 34 etaient des femmes (95 %). L’âge moyen etait de 28 ans ± 11, l’IMC moyen a l’admission etait de 12 ± 2,0, On a observe a l’admission une cytolyse hepatique chez 17 (46 %) patients. Leur IMC a l’admission etait de 10,9 ± 1,4; leur âge 25,4 ± 18. Ils presentaient une augmentation moyenne des ASAT a 8N, mediane (Extreme) 84 (46-1620), et ou des ALAT a 8N, mediane (Extreme) 215 (57-2614).L’evolution du bilan hepatique a la fin de la premiere semaine apres la mise en route d’une alimentation enterale progressive, associee a une supplementation en vitamines, oligoelements et phosphore etait favorable chez 16 des 17 patients (94 %) avec une moyenne des ASAT a 3N, mediane (Extreme) 65 (29-225) et Des ALAT a 4N, mediane (Extreme) 137 (55-1129). La normalisation totale du bilan hepatique est observee a la 4 e semaine d’hospitalisation. Une seule patiente a cependant presente une aggravation secondaire des transaminases sous alimentation entrale apres amelioration initiale avec des ASAT 10N et ALAT 8N a la 4 e semaine, un retour a des valeurs normales est observe au bout de la 7 e semaine ; elle avait par ailleurs presente une hypophosphoremie majeure a l’admission et un TP a 40 %. L’IMC moyen des patients presentant une cytolyse hepatique etait de 11,7 ± 1,6 a la 4 e semaine.Les patients n’ayant pas presente de cytolyse hepatique a l’admission, etaient âges de28 ans ± 11.Leur IMC a l’admission etait de 13,4 ± 2 et a 14 ± 2a la 4 e semaine de renutrition. Le reste du bilan hepatique etait peu perturbe. Conclusions Pres de la moitie des patients denutris severes atteints d’anorexie mentale admis pour renutrition enterale presentent une augmentation systematique des transaminases, ils avaient a l’admission un IMC inferieur et etaient plus jeunes que les patients ayant un bilan hepatique normal. L’evolution est rapidement favorable des la premiere semaine d’hospitalisation dans la majorite des cas. La normalisation des transaminases parallelement a la prise de poids a concerne tous les patients au terme d’un mois d’alimentation enterale progressive associee a une supplementation en vitamines et oligo-elements. Par ailleurs, une meilleure connaissance des mecanismes a l’origine des perturbations du bilan hepatique necessiterait certainement des etudes prospectives plus completes chez les patients atteints d’anorexie-mentale.

In order to test the hypothesis that a combination of protease inhibitors with nucleoside analogues-agents known to inhibit different steps of the human immunodeficiency virus (HIV) life cycle--is likely to prove more effective in reducing viral loads than either of those modalities alone, we performed a 60 week, open-label trial in 32 HIV-positive patients with depressed CD4 T lymphocyte cell counts but no active AIDS-defining illnesses. For the first 2 weeks, patients received 600 mg twice daily of liquid ritonavir, a protease inhibitor; then zidovudine 200 mg three times daily and zalcitabine 0.75 mg three times daily were added to the treatment regimen. Mononuclear blood cell fractions were analysed for infected cell levels, using a co-culture system. HIV-1 RNA in plasma was measured both by reverse transcriptase-polymerase chain reaction (RT-PCR) and reverse transcriptase quantitative PCR (QcRT-PCR); lymphocyte counts were determined by standard laboratory methods. In the 2 weeks of ritonavir therapy, both the mean count of infectious blood cells and plasma HIV RNA levels decreased dramatically. Mean CD4 cell counts increased from 173 cells/mm3 at baseline to 286 cells/mm3; CD8 cell counts rose from 951 cells/mm3 to 1,141 cells/mm3. With the introduction of the nucleoside analogues, infectious cell counts and plasma virus dropped another log unit to a nadir at 8 weeks, while CD4 T lymphocyte counts continued to rise slowly. By week 28, 12 patients had withdrawn due to adverse events, none of which were life-threatening. At week 36, infectious material could not be detected in the cells of 10 of the 17 remaining patients; by week 60, four of the seven patients with residual viraemia at week 24 had undergone viral relapse. After the introduction of a more palatable capsule formulation of ritonavir at week 52, infectious cells and plasma virus were undetectable in 50-60% of patients. The combination of protease inhibitors and nucleoside analogues significantly reduces HIV load, and in some patients may suppress viral activity for sustained periods.

Fungal infections of the central nervous system are uncommon in human immunodeficiency virus infected patients. The most frequently encountered is cerebromeningeal cryptococcosis. We report 3 clinicopathological cases of rarer fungal infections of the central nervous system in AIDS patients due to Candida and Aspergillus genders. In most cases, a systemic candida infection or aspergillus pulmonary infection preceded the onset of cerebral granulomas or abscesses. These infections usually occurred at the terminal stage of the disease and were associated with other neuropathologies. Neutropenia associated with lymphopenia represents a frequent risk factor along with intravenous catheter.

Infections of the central nervous system by Herpes simplex viruses (Herpes simplex type 1 and Herpes simplex type 2) are uncommon in acquired immune deficiency syndrome and are often clinically and pathologically atypical. We have collected 11 cases of herpes simplex encephalomyelitis in AIDS patients reported in the literature. Only 3 of these cases presented with a typical, necrotizing, limbic encephalitis. Other clinicopathological patterns included ventriculitis, rhombencephalitis and myelitis. Ventriculitis and rhombencephalitis were usually due to infection by HSV-1, whereas myelitis was mostly due to HSV-2 infection. Distinction between the 2 types of virus is often difficult by immunohistochemistry due to frequent cross reactivity and usually requires tissue culture, in situ hybridization, or polymerase chain reaction. Association of HSV encephalomyelitis with productive infection of the central nervous system by the human immunodeficiency virus was only found in one case. In contrast, co-infection with cytomegalovirus was found in 9 of the 11 cases. One case also had had varicella zoster virus vasculitis, and another case also had a cerebral malignant non Hodgkin's lymphoma in which Epstein Barr virus genome was identified. This supports the view that concomitant herpes-virus infections of the central nervous system is a characteristic feature of AIDS.

We have reviewed 23 cases of varicella-zoster virus infection of the central nervous system in patients with the acquired immunodeficiency syndrome, previously reported in the literature, including 11 from our own series. This allowed us to identify 5 clinico-pathological patterns which could occur simultaneously. In most cases, viral proteins or viral genome were identified using immunocytochemistry or in situ hybridization. Multifocal encephalitis involves predominantly the white matter and is likely to be due to haematogenous spread of the infection. Ventriculitis may have variable appearance according to the course of the disease. In one incipient case, the ependymal lining appeared irregular with foci of infected ependymal cells some of which protruded into the ventricular lumen; in other instances, there was acute or chronic necrosis of the ventricular wall with marked vasculitis. Acute haemorrhagic meningo-myelo-radiculitis with necrotising vasculitis may be associated with ventriculitis and results from shedding of infected ependymal cells into the ventricular lumen and secondary seeding of the cerebrospinal fluid. Focal necrotising encephalitis or myelitis usually follows cutaneous herpes zoster in the corresponding dermatoma and is considered to result from neural spread from the diseased trigeminal or dorsal root ganglion. Vasculopathy involving leptomeningeal arteries and causing cerebral infarcts is associated with meningitis in most cases. These findings are in keeping with the observation in other immunocompromised patients, that varicella-zoster virus spread to the central nervous system may follow different routes. Our study tends to show that varicella-zoster virus infection of the central nervous system is more frequent in the acquired immunodeficiency syndrome than previously suspected and suggests this diagnosis must be considered systematically in cases of encephalitis, ventriculitis, focal myelitis, acute myeloradiculitis and cerebral infarcts in these patients, since an efficient treatment is available.

Herpetic esophagitis (HE) associated with human immunodeficiency virus (HIV) is a rare condition mainly reported as isolated cases. We thus decided to study this association and analyze the possible predisposing factors, clinical and endoscopic presentations, and clinical response to treatment. Thirty-four HIV-1-infected patients were identified: 27 had histologically or virologically confirmed HE and seven had probable HE, a retrospective diagnosis based on the efficacy of acyclovir given alone. The median CD4 cell count was 15/mm3. Recent predisposing factors (such as nasogastric procedures, steroid therapy, and anticancer therapy) were noted with regard to 16 of the 34 patients (47%). Odynophagia and/or chest pain occurred in 30 patients (88%). At the time of diagnosis of HE, extraesophageal herpes was found in only 13 patients (38%). Superficial ulcers of the distal third of the esophagus were present in 17 (50%). Among 20 of the 27 patients with confirmed HE that could be evaluated, therapy with acyclovir led to complete resolution in 16 and partial response in 3; 1 patient died of HE. Five patients (15%) suffered confirmed or possible relapses. The mean interval between the diagnosis of HE and death was 8.8 months. Herpes simplex virus may be responsible for ulcerated esophagitis that occurs in the advanced stages of AIDS and that can be safely treated with acyclovir before a definitive diagnosis is made.

Eighty patients were followed up prospectively. Histological correlation was obtained in 25 cases. All MRI examinations were performed on at 0.5 Tesla in T1-weighted sequences with and without gadolinium injection, and in axial or frontal T2-weighted spin echo sequences. Histological confirmation was obtained 30 days on average after the last MRI examination. Immunohistochemical stainings were performed in search of CMV, VZV, toxoplasma, HIV antigen and lymphoma.CMV meningoencephalitis was found in 6 cases. In 3 of these it was manifested by atrophy, either isolated or associated with high signal intensity punctiform areas. Histology detected cortical or subcortical microglial nodules. In 2 cases MRI displayed abnormalities of subependymal nodular signals without enhancement, associated with punctiform abnormalities of subcortical signals. Histology showed subependymal foci of necrosis and abnormalities of white matter. In one case, MRI showed a ventriculitis confirmed by histology. VZV meningoencephalitis was diagnosed in 2 cases. MRI displayed abnormal basal ganglia related to meningitis (n = 1). All abnormalities were confirmed at histology.Some images (ventriculitis, infarction in basal ganglia, abnormal subependymal signal) would suggest VZV and CMV encephalitis. Other images (abnormalities of punctiform signals or atrophy) are not specific.

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.

A 36 years-old male with AIDS, presented with left hemiparesis revealing a right parietal tumour. Stereotactic biopsy demonstrated a malignant non-Hodgkin's lymphoma. His condition partially improved following radiotherapy and chemotherapy. Three months later he was re-admitted with progressive bilateral root pain and urinary incontinence resulting in paraplegia with sensory loss below T10. He died one month later from generalized sepsis. Neuropathology confirmed an immunoblastic B-cell malignant non-Hodgkin's lymphoma in the white matter of the right parietal lobe and revealed a centrospinal localisation of the lymphoma in the thoracic cord at T10. There was no visceral localisation of the tumour. Secondary spread to the spinal cord of malignant non Hodgkin's lymphomas, usually causes meningo-myelo-radiculitis. Intraspinal deposits of primary cerebral lymphomas are uncommon and have never been previously described in AIDS, to our knowledge. Their pathogenesis is unclear. In our case, neuropathological findings are consistent with diffusion of the primary tumour to leptomeninges and secondary infiltration of the spinal cord along the perivascular spaces.

Introduction La citrullinemie est un biomarqueur innovant de la masse enterocytaire [1]. Elle constitue un parametre integre de la fonction absorptive globale de la muqueuse intestinale en situation chirurgicale, medicale et oncologique. Cependant les donnees evolutives sont rares, la majorite des etudes etant transversales. But determiner la citrullinemie, son evolution et sa valeur pronostique, dans les enteropathies medicales immunologiques, infectieuses et toxiques. La maladie VIH a ete prise comme modele. Patients et Methodes Trois groupes de patients (n = 53 ; 43H, 10F ; 43 (24 - 68) ans) ont ete prospectivement suivis pendant une duree mediane de 16 (6 - 37) mois avec 3 (2 -15) dosages, selon le contexte : 1) patients sans signes digestifs (n = 16) ; 2) patients non immunodeprimes (CD4 > 200/mm3) ayant une diarrhee du fait d’un effet toxique du traitement antiretroviral (ARV) (n = 12) ; 3) patients immunodeprimes (CD4 Resultats Chez les patients sans signes digestifs la citrullinemie ne se modifiait pas (36 ± 6 μmol/L vs 38 ± 8 chez les controles). Lors de gastro-enterite aigue de rencontre (n = 4) la citrullinemie baissait (19 ± 5 vs 34 ± 7) puis revenait a sa valeur basale en moins d’un mois. Lors d’enteropathie toxique, la citrullinemie augmentait quand l’ARV pouvait etre arrete ou substitue (n = 6, 22 ± 4 vs 42 ± 14, P 10). Aucun seuil ne pouvait etre determine pour la nutrition enterale (n = 10). Une correlation (P 6 mois d’une citrullinemie 20, P Conclusion La citrullinemie constitue un marqueur fiable de la fonction enterocytaire et de son evolution au cours des traitements specifiques. Elle determine les consequences fonctionnelles des enteropathies et notamment l’indication d’une nutrition parenterale. Elle constitue de plus un marqueur pronostique defavorable si elle reste inferieure a 20 μmol/L.

Introduction L’existence de perturbations des tests hepatiques dans l’anorexie mentale (AM) est decrite. La physiopathologie et la gravite potentielle de cette atteinte hepatique sont mal connues. L’objectif de ce travail a ete d’analyser les anomalies des tests hepatiques au cours des denutritions graves chez les patients atteints d’AM, d’identifier les facteurs de risque de survenue et d’observer leur evolution au cours de la renutrition. Patients et Methodes Etude retrospective sur un echantillon de patients AM hospitalises pour renutrition entre 1996 et 2006. Une perturbation du bilan hepatique a ete definie par une augmentation des ASAT et/ou des ALAT > 2N. Criteres d’inclusion : AM (definition DSM-IV), denutrition definie par un indice de masse corporelle (IMC) 18. Resultats Soixante six patients ont ete inclus. Sex ratio 62 F/4 H. AM restrictive pure 42 (63,6 %), des conduits purgatives associees 24 (36,3 %). L’âge moyen etait de 28,7 ± 11 ans, IMC 12,3 ± 1,9, albuminemie 36,7 ± 7 g/L. Tous les patients ont beneficie d’une renutrition progressive (enterale et/ou orale), selon les besoins calcules, associee a une complementation en vitamines, oligo-elements et phosphore. Plus de la moitie des patients (39, 59 %), IMC 12,9 ± 2,0, âge 30,6 ± 12, n’avait pas de cytolyse hepatique a l’admission. Aucun de ces patients n’a secondairement developpe d’hypertransaminasemie. Il existait une cytolyse a l’admission chez 41 % (n = 27) des patients, 78 % presentaient une AM restrictive pure, IMC 11,4 ± 1,9 ; âge 25,9 ± 7 ans. Ils presentaient une augmentation mediane des ASAT a 4N (extremes 2N-57N) et des ALAT a 4N (2N- 44N). Ces patients avec cytolyse avaient un IMC inferieur (P Conclusion La cytolyse hepatique est retrouvee pres d’une fois sur 2 dans l’AM au cours des denutritions severes. Quatre facteurs de risque ont pu etre identifies : âge jeune, homme, IMC bas et forme restrictive pure de maladie. L’evolution est le plus souvent benigne mais peut etre plus severe dans moins de 5 % des cas. Les facteurs de risque d’une evolution defavorable restent a identifier.

Apres une hepatite aigue C, une guerison survient spontanement dans 25 % des cas ; l’ARN plasmatique du VHC disparait dans les 6 premiers mois. La persistance de la viremie VHC apres 6 mois traduit le passage a la chronicite. De rares cas de guerison spontanee d’hepatites chroniques C ont ete decrits. Cas cliniques Nous en rapportons 4 cas chez des patients co-infectes par le VIH et le VHC. Il s’agit de 3 femmes et 1 homme d’âge moyen 42 ans, tous anciens usagers de drogue par voie veineuse qui avaient arrete la toxicomanie au profit d’une consommation importante d’alcool. L’infection VIH etait connue depuis en moyenne 13 annees, la serologie VHC positive etait connue depuis en moyenne 7 annees (genotype 4 deux patients, genotype 1 et 3 un patient chacun, charge virale VHC moyenne = 4,87 log). Chaque patient a eu plusieurs PCR VHC positives (2 a 4) accompagnees de transaminases elevees (moyenne 2 × N). La PCR est ensuite devenue negative jusqu’a ce jour (moyenne 4 determinations, recul moyen = 3 ans). Ces 4 guerisons ont ete observees apres mise sous tritherapie antiretrovirale (50 mois en moyenne). Lors de la negativation de la PCR VHC, le gain de CD4 etait de +270/mm 3 par rapport au nadir. Les 4 patients etaient devenus abstinents d’alcool depuis quelques mois. Discussion La guerison spontanee de l’hepatite chronique C apres restauration immunitaire et arret de l’alcool merite d’etre recherchee. Cette constatation plaide pour la mise sous tritherapie antiretrovirale et pour la promotion du sevrage alcoolique avant decision du traitement de l’hepatite C chez les patients co-infectes VIH/VHC.

Dans les pays en developpement, l’acces aux anti-retroviraux pour les patients infectes par le VIH est en constante progression. La malnutrition y est aussi tres frequente et represente une autre cause d’immunodeficience acquise. Objectif Cette etude avant/apres a evalue l’impact d’un appui nutritionnel standardise (ANS ; type blanket feeding) associe a une tritherapie anti-retrovirale (HAART) chez des patients infectes par le VIH a Niamey, Niger. Methode Le suivi clinico-biologique pendant 6 mois de 64 patients recevant l’ANS associe a une HAART, a ete compare a celui de 131 patients ayant seulement recu une HAART l’annee precedente. Resultats Dans le groupe recevant l’ANS, 3 patients decedaient contre 15 dans le groupe temoin (Ratio de Mortalite = 0,30 [0,05 ; 1,0]) ; la persistance d’infections opportunistes non resolutives etait reduite RR = 0,31 [0,11 ; 0,87] ; l’augmentation des lymphocytes T CD4+ etait 1,6 fois plus importante (p Conclusion Cette etude montrait un impact favorable de l’ANS des six mois de supplementation, associe a une HAART chez des patients infectes par le VIH dans un pays en developpement. L’impact etait observe sur les plans clinique, immunologique et sur l’observance. L’amelioration de l’observance etait le meilleur signe de la portee sociale de l’ANS associee a la HAART. L’ANS devrait etre propose le plus largement possible pour les patients infectes par le VIH dans les pays en developpement.

Un taux insuffisant d'inhibiteurs proteiques (IP) peut etre la cause de l'echec d'un traitement antiretroviral hautement actif (HAART). Objectifs Etablir une correlation entre la teneur en indinavir (IDV) dans les cheveux preleves (capillogramme) et la reponse virologique au traitement comprenant de l'IDV. Methodes Trente patients naifs d'IP avec viremie VIH positif, ont suivi un HAART comprenant de l'IDV. Le jour du prelevement des cheveux, les patients etaient classes comme repondeurs (R) ou non-repondeurs (NR) (viremie > 200 copies/mL). Une meche de cheveux prelevee au ras du crâne a ete coupee en segments de 2 cm. La teneur en IDV a ete mesuree par Chromatographie. Chez les NR, l'emergence de mutations significatives du gene de la protease (IDV) a ete recherchee. Resultats Dix-neuf patients etaient R et 11 NR. Dans les 2 cm proximaux de cheveux, le capillogramme d'IDV etait plus haut chez les R que chez les NR (moyenne + ecart-type : 17,85 + 5,08 contre 8.01 + 5,39 g/g) et de meme dans les segments plus distants. Aucune mutation du gene de la protease (IDV) n'avait ete detectee avant le HAART; 8 souches sur 11 des NR ont ete sequencees. Les 3 NR avec un haut capillogramme d'IDV (> 10 g/g) avaient des souches mutees pour le gene de la protease. Parmi les 5 NR a bas capillogramme d'IDV, 3 avaient des souches sensibles a l'IDV et 2 avaient des souches mutees. Conclusion Le capillogramme d'IDV permet d'aider a guider le traitement des patients VIH ne repondant pas a un HAART