Acute microbiologically negative hypoxic interstitial pneumonia on HAART: Immune Reconstitution Inflammatory Syndrome unmasking Pneumocystis jiroveci infection with an atypical presentation.

Highly active antiretroviral therapy for AIDS sometimes engenders inflammatory manifestations resulting from an inappropriate and unbalanced immune-system restoration, called Immune Reconstitution inflammatory Syndrome, which, in turn, can unmask a subclinical infection/pathology. Despite our patient's evident syndrome, the atypical clinical, microbiologic and radiologic feature of Pneumocystis pneumonia made its diagnosis difficult.

[Rifampin-induced severe aseptic meningitis]. / Méningite aseptique sévère induite par la rifampicine.

We report the first case of acute drug-induced aseptic meningitis (DIAM) due to rifampin in a young female with systemic lupus erythematosus (SLE). DIAM is uncommon and its diagnosis is often difficult. This type of drug hypersensitivity is more frequently observed in patients with a history of auto-immune disease, particularly SLE. The major categories of causative agents are: nonsteroidal anti-inflammatory drugs, antimicrobials, intravenous immunoglobulins and biotherapies.

[From retroperitoneal fibrosis to gastric linitis]. / De la fibrose rétropéritonéale à la linite gastrique.

Retroperitoneal fibrosis may reveal many diseases, including neoplasias. An 83-year-old man presented with an acute renal failure due to compressive retroperitoneal fibrosis. Clinically the only abnormal feature was a cutaneous subclavicular infiltrated lesion and laboratory features included hypereosinophilia, anemia and elevated acute phase reactants. A thoracic CT-scan showed pleuritis and para-esophageal lymph node and the 18FDG-PET-scan an hypermetabolism lesion of the oesophagus. Gastroscopy and colonoscopy found a gastric linitis, already multi-metastatic at diagnosis. The gastric linitis can present with many decepting clinical forms, increasing the risk of delayed diagnosis.

Anti-PGL-Tb1 responses as an indicator of the immune restoration syndrome in HIV-TB patients.

A prospective and multi-centre study has allowed us to analyse antibody responses and Mycobacterium tuberculosis clinical isolate genotypes on 24 consecutive HIV-TB co-infected patients treated with Highly Active Antiretroviral Therapy (HAART) who either went on to develop a TB Immune Restoration Syndrome (TB-IRS), or not. Circulating free and immune-complexed antibodies against ManLAM, ESAT-6/CFP10 and PGL-Tb1 in HIV-TB co-infected patients were measured by ELISA at the initiation of anti-TB treatment, at the date of HAART initiation and thereafter. Presence of circulating B cells was also monitored by in vitro antibody production (IVAP) against ESAT-6/CFP10 and PGL-Tb1. Finally, 16 out of 24M. tuberculosis clinical isolates from patients with TB-IRS were genotyped using spoligotyping and MIRUs-VNTR typing. Eleven patients (45.8%) experienced TB-IRS (TB-IRS+). Significantly, lower anti-PGL-Tb1 antibody levels were identified in TB-IRS+ compared to TB-IRS-negative patients prior to TB-IRS development. These very low levels were neither related to CD4 counts nor with complexed antibodies. No difference in antibody levels was observed with the other tested antigens. In addition, no specific strain genotype was associated with TB-IRS. The presence of specific anti-PGL-Tb1 antibodies only in TB-IRS-negative patients represents for the first time an indicator of a potential protective response or a diagnostic biomarker for the detection of non-progression to TB-IRS in HIV-TB co-infected patients starting HAART.

Hepatitis B virus-human immunodeficiency virus co-infection in France: a cross-sectional multicentre study.

This prospective, multicentre study was conducted between September and October 2003 in 38 French departments of internal medicine, infectious disease and hepatogastroenterology and included 406 consecutive HBV-infected patients (positive HBsAg), half of whom were HIV-infected (53%). The aim was to outline the main characteristics of hepatitis B virus (HBV)-human immunodeficiency virus (HIV) co-infected patients in French hospitals. HBV-HIV co-infected patients (85% were receiving HAART; mean CD4 count 447+/-245/microl, HIV RNA load<400 copies/ml, 67% of patients), compared to HIV-negative patients, were more often male, injecting drug users, HBeAg-positive and HCV-HIV co-infected (P<10(-4)). They underwent liver biopsy less often (31% vs. 51%, P<10(-4)), particularly those with severe immunodeficiency. They received anti-HBV treatment more often (75% vs. 45.7%, P<10(-4)), mainly lamivudine and tenofovir. Significant improvements in the management of such patients are awaited mainly in the appraisal of liver disease by either liver biopsy or non-invasive alternatives to liver biopsy.

Impact of pain in health related quality of life of patients with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) has an heterogenous clinical pattern, with variable organ involvement and degrees of severity. Like in other rheumatic diseases, the self-questionnaires have been used to evaluate SSc globally. The aim of the study is as to evaluate the quality of life (QoL) in patients with either diffuse or limited SSc, and to examine the impact of pain on the QoL scores. METHODS: Patients with SSc, either diffuse or limited SSc, were included in a cross-sectional study. The QoL was evaluated with the short-form 36 (SF-36) and the functional repercussion with the SSc-modified Health Assessment Questionnaire (S-HAQ). RESULTS: A total of 89 patients (67 with diffuse and 22 with limited SSc) were included. The SF-36 score values were lower in SSc patients than those reported in the general population. The physical component scores (PCS) of the SF-36 was significantly worse in diffuse compared with limited SSc (P < 0.05). The PCS was significantly negatively related to the number of clinical manifestations (ANOVA, P < 0.0001). The mental component score (MCS) was not influenced by the type of SSc or the number of clinical manifestations presented by the patient. The QoL of SSc patients was highly correlated with pain (R = 0.69) and disability (R = 0.70). Interestingly, the QoL of SSc patients was only slightly correlated with cutaneous (R = 0.42) and pulmonary involvement (R = 0.57). CONCLUSION: The QoL of patients with SSc is strongly influenced by the type of SSc, the burden of clinical manifestations, the functional disability and by the pain, whatever its cause. The treatment of pain should be considered as priority to improve the QoL of SSc patients.

Factors associated with virological response in HIV-infected patients failing antiretroviral therapy: a prospective cohort study.

OBJECTIVES: To assess the antiviral response to optimized therapy following genotypic resistance testing and to identify factors associated with virological response in HIV-1-infected patients failing antiretroviral therapy. METHODS: A prospective cohort study was conducted in 344 HIV-1-infected patients who underwent genotypic resistance testing because of virological failure. Virological response was defined as a plasma HIV RNA level below 200 HIV-1 RNA copies/mL or a drop of plasma viral load from baseline of more than 1 log10. A multivariate logistic regression analysis was performed to identify factors associated with virological response. RESULTS: The median age of the patients was 40 years, with a male to female ratio of 4:1. Fifty-one per cent of patients had received the three major classes of antiretrovirals and the median duration of previous antiretroviral therapy was 4.6 years. At baseline, the median plasma HIV RNA level was 4.4 log10 copies/mL and the median CD4 cell count was 274 cells/microL. At 3 months, 55% of patients (188 of 344) had a virological response, which was sustained at 6 months (53%). Predictors of virological response were exposure to two or fewer protease inhibitors [odds ratio (OR) 1.8; P=0.046], and use in optimized therapy of a new class of antiretrovirals (OR 2.9; P=0.006), of more than two new drugs (OR 3.0; P<0.0001), of abacavir (OR 1.9; P=0.03), or of lopinavir/ritonavir (OR 3.7; P=0.0002). CONCLUSIONS: A high proportion of patients achieved a short-term virological response in this cohort study. Patients with the least experience of protease inhibitor treatment and in whom a new class of antiretroviral, more than two new drugs, abacavir or lopinavir/ritonavir was used in optimized therapy had the best virological outcome.

Validation of French version of the Scleroderma Health Assessment Questionnaire (SSc HAQ).

The modified Scleroderma Health Assessment Questionnaire (SSc HAQ) is a functional score to assess systemic sclerosis (SSc) comprising the HAQ disease index (HAQ-DI) plus five specific visual analogue scales (VAS). Since it was validated in English-speaking patients only, its general use in any other language necessitates prior cross-cultural adaptation and validation. We designed this study to assess its value in French-speaking patients and to validate the French version according to international recommendations. We elaborated a French version using the "forward-backward" method. We then validated its psychometric properties with 100 consecutive SSc French-speaking patients who had undergone simultaneous clinical and paraclinical examination. In addition, we calculated the SSc HAQ score, a new outcome measure, which is obtained by pooling the eight domains from the HAQ-DI with the five organ VAS. Our study confirmed the psychometric properties of the SSc HAQ in non-English-speaking patients with (a) structural validity: the major component analysis, performed on the HAQ-DI and the five VAS, yielding a two-factor structure; (b) convergent validity: with high correlation coefficients between the SSc HAQ score and the physical component score of the SF-36 (r=-0.74, p<0.0001); (c) discriminant validity: the SSc HAQ score was better in patients with limited than with diffuse SSc (0.5+/-0.5 vs 1.1+/-0.7, respectively, p<0.0001) in relation to the number of clinical involvements; (d) reproducibility was high using the test-retest procedure (r=0.98). This study showed the value of the SSc HAQ, which is a simple, discriminant, reproducible self-administered questionnaire to evaluate French-speaking SSc patients. In addition, we suggest the use of a new outcome measure, the SSc HAQ score, to assess this systemic disease more accurately.

[Medical practice analysis in internal medicine: a national descriptive study]. / Analyse des pratiques des spécialistes de médecine interne: une enquête transversale descriptive nationale.

PURPOSE: This descriptive and epidemiological study was conducted in Mars 2002 in Internal Medicine in order to (1) participate in elaborating a White Book about the speciality, (2) analyse the post-university formation needs of the specialists in Internal Medicine. METHODS: A questionnaire was sent to all specialists in Internal Medicine listed on the ADELI file (n = 2155). For the first three patients seen in consultation and during hospital stay, questioned specialists had to mention the age, sex, origin, motive of the visit, nature of symptoms, complexity of the problem and the nature of the required abilities. They also had to precise the main diagnosis of all patients seen in the same day. RESULTS: Three hundred and sixty answers have been received. Three hundred and thirty two were exploitable. Five thousand six hundred and eleven main diagnosis were listed. Fifteen percent of the questioned specialists did practise in other specialities than Internal Medicine. Orphaned diseases were the most common pathologies carried out in consultation (17%). Patients seen during their hospital stay suffered more frequently from infectious, haematological and malignant diseases. In 55% of the cases, patients were seen in second or third line after a visit to a general practitioner or another specialist. The abilities of the Internal Medicine specialist alone were sufficient in 70% of the cases to solve the problem. Complexity of the problem was evaluated by the specialists themselves at about 45/100 on an analogical scale. CONCLUSIONS: This study inform the medical community about the type of patients treated by the specialists in Internal Medicine, precise the exact nature of their professional exercise and their real need in medical post-university formation.

Thoracic disk herniation mimicking renal crisis.

A 45-year-old-woman presented with a mimicking renal stone colicky pain that was finally attributed to radiculalgia T12 caused by a calcified T11-T12 disk herniation.

Pharmacokinetics of emtricitabine, didanosine and efavirenz administered once-daily for the treatment of HIV-infected adults (pharmacokinetic substudy of the ANRS 091 trial).

OBJECTIVE: This study was conducted to investigate the pharmacokinetics of emtricitabine (FTC), didanosine (ddI), and efavirenz (EFV) when administered in a once-daily combination. METHODS: Nine antiretroviral-naïve HIV-infected adults who received FTC [200 mg once a day (q.d.)], ddI (400 mg q.d. if > or =60 kg; 250 mg q.d. if <60 kg) and EFV (600 mg q.d.) were studied. The following pharmacokinetic (PK) parameters were determined over 24 h at steady-state after 4 weeks of treatment: area under the plasma concentration vs. time curve (AUC(0-24 h)), maximum (Cmax) and minimum (Cmin) plasma concentrations, time to reach Cmax (Tmax), and the elimination half-life (t(1/2)). EFV plasma concentrations were also measured during follow-up. RESULTS: Median PK parameters for FTC, ddI and EFV, respectively, were as follows. AUC(0-24 h): 7.2, 7.0 and 36.4 h x mg/L; Cmax: 1.8, 2.6 and 2.5 mg/L; Cmin: 0.04, <0.01 and 1.0 mg/L; Tmax: 1.8, 1.1 and 2.5 h; t(1/2): 7.4, 2.3, and 23.7 h. EFV plasma concentrations measured 10-13 h postdosing were higher during follow-up than during the PK study (2.57 vs. 1.19 mg/L, P<0.01). CONCLUSION: The simultaneous administration of FTC, ddI and EFV did not affect the PK parameters of FTC when compared to historical controls. EFV Cmax and Cmin were lower than expected, but the data may have been slightly underestimated in this study. High ddI AUC and Cmax were measured in these patients, and further studies are warranted to confirm this finding.

[Quality of life assessment with the MOS-SF36 in patients with systemic sclerosis]. / Evaluation de la qualité de vie par le MOS-SF36 dans la sclérodermie systémique.

OBJECTIVE: To investigate the metric properties and the validity of the Medical Outcome Study Short Form 36 (SF-36), a questionnaire to assess the quality of life, in patients with either diffuse or limited systemic sclerosis (SS), and to examine the effect of the disease on quality of life. METHODS: Cross sectional study of 86 patients with a SS (64 diffuse SS, 22 limited SS). Disease severity was assessed by clinical examination, pulmonary functional tests and Health Assessment Questionnaire (HAQ) modified for scleroderma. RESULTS: The SF-36 scores values were lower in diffuse than in limited sclérodermie systémique. The Physical Component Score was worse in patients with than without any clinical involvement. This score increased in relation with the number of clinical involvements. The quality of life of patients with SS was correlated to its functional repercussion. CONCLUSION: The quality of life in SS patients is correlated with the clinical severity of the disease. The use of SF-36 to measure the quality of life is useful for the clinical evaluation of patients with SS.

Rapid efficacy of highly active antiretroviral therapy in a case of HIV myelitis.

An HIV-seropositive patient with severe immunodepression was diagnosed as having HIV myelitis. Plasma and cerebrospinal fluid (CSF) HIV-RNA PCR were, respectively, 4.11 and 5.19log(10). After 1 month of treatment with highly active antiretroviral therapy (HAART), there was clinical recovery and both plasma and CSF HIV viral load had decreased considerably. This dramatic improvement was associated with a high concentration of antiviral drugs in the CSF, suggestive of the direct efficacy of HAART on HIV myelitis.

Preferential and persistent depletion of CCR5+ T-helper lymphocytes with nonlymphoid homing potential despite early treatment of primary HIV infection.

Strains of human immunodeficiency virus (HIV) transmitted between individuals use the CCR5 coreceptor, but no preferential depletion of particular Th-lymphocyte subpopulations has been reported during primary HIV infection (PHI). In contrast, gut-associated Th lymphocytes are preferentially depleted in macaques recently infected by simian immunodeficiency virus. The expression of CCR5 and the intestinal homing receptor integrin alpha4beta7 on subpopulations of Th lymphocytes was studied in 12 patients with PHI. There was a profound decrease of circulating alpha4beta7+ Th lymphocytes and CCR5+ memory Th lymphocytes with nonlymphoid homing potential (CD62L-CD45RO+). Unlike other Th lymphocytes, this cell population remained depleted despite early control of viral replication under antiretroviral treatment. Therefore, HIV preferentially targets a specific CCR5+ subpopulation of Th lymphocytes early during infection, inducing its persistent depletion despite treatment. Protective immunity in vivo depends on Th lymphocytes carrying homing capacity to nonlymphoid tissue, and therefore these data may explain the persistent abnormalities of immune functions in patients infected with HIV.

A dose-ranging study to evaluate the antiretroviral activity and safety of amprenavir alone and in combination with abacavir in HIV-infected adults with limited antiretroviral experience.

OBJECTIVE: To evaluate the antiretroviral activity and safety of multiple escalating doses of amprenavir administered alone, and in combination with abacavir in HIV-1-infected adults. DESIGN: Sixty-two HIV-1-infected subjects were enrolled in a multicentre, open-label, non-randomized, dose-escalating trial. METHODS: Subjects were assigned to one of six dose groups and received amprenavir 300 mg twice daily, 300 mg three times daily, 900, 1050, or 1,200 mg twice daily for 4 weeks. One dose group received amprenavir 900 mg twice daily in combination with abacavir 300 mg twice daily for 4 weeks. Antiretroviral activity was assessed by measuring changes from baseline in plasma HIV-1 RNA levels and CD4 cell counts. Safety was evaluated by monitoring clinical adverse events and changes in laboratory values. Genotypic and phenotypic analyses were performed using ABI sequencing and the recombinant virus assay, respectively. RESULTS: At week 4, amprenavir monotherapy (900, 1,050, or 1,200 mg twice daily) resulted in marked decreases in plasma HIV-1 RNA levels (1.3-1.6 log10 copies/ml), and substantial increases in CD4 cell counts in the two dose groups who received 1,050 mg twice daily (118 x 10(6) cells/mm3) or 1,200 mg twice daily (114 x 10(6) cells/mm3). Amprenavir/abacavir resulted in median plasma HIV-1 RNA reductions of 1.8 log10 copies/ml, and median CD4 cell count increases of 138 x 10(6) cells/mm3. Amprenavir was reasonably well tolerated with few treatment-limiting adverse events. No known active site mutations associated with amprenavir resistance were selected in any of the dose groups, and no significant phenotypic resistance to amprenavir developed during 4 weeks of therapy. CONCLUSIONS: The antiviral effect of amprenavir monotherapy increased with escalating doses, and all amprenavir doses were reasonably well tolerated over 4 weeks of therapy. Amprenavir/abacavir combination therapy elicited a potent antiviral effect. The three highest doses of amprenavir (900, 1,050 and 1,200 mg twice daily) were selected to design subsequent Phase II and III studies that confirmed the safety profile and efficacy of amprenavir in combination regimens and led to the approval of amprenavir in the USA in 1999.

Early control of HIV replication in primary HIV-1 infection treated with antiretroviral drugs and pegylated IFN alpha: results from the Primoferon A (ANRS 086) Study.

IFN alpha has both antiviral and immunostimulating properties. The ANRS086 Primoferon A Study evaluated in 12 patients with primary HIV infection the tolerance and efficacy of an early and transient administration of pegylated IFN alpha, in addition to highly active antiretroviral therapy. Tolerance was good, and this regimen allowed the early control of HIV replication and rapid decay of the viral reservoir. These results support the initiation of comparative studies with pegylated INF alpha in primary HIV infection.