Satisfaction with care in HIV-infected patients treated with long-term follow-up antiretroviral therapy: the role of social vulnerability.

The aim of this study was to determine factors associated with complete satisfaction with the care provided (satisfaction with physicians and satisfaction with services and organization) among HIV-infected patients followed up in the French ANRS CO8 APROCO-COPILOTE cohort. Analyses focused on cross-sectional data collected during the ninth year of cohort follow-up. Satisfaction with care, sociodemographic characteristics, and behavioral data were collected using self-administered questionnaires, while clinical data were derived from medical records. Complete satisfaction with care was defined as being 100% satisfied. Two logistic regression models were used to identify predictors of (1) complete satisfaction with physicians (n=404) and (2) complete satisfaction with services and organization (n=396). Sixteen percent of patients were completely satisfied with physicians, while 15.9% were completely satisfied with services and organization. Being older and reporting fewer discomforting antiretroviral therapy (ART) side effects were factors independently associated with complete satisfaction with both physicians and services and organization. Strong support from friends and absence of hepatitis C (HCV) co-infection were independently associated with complete satisfaction with physicians, while strong support from one's family and comfortable housing conditions were independently associated with complete satisfaction with services and organization. Even after nine years of follow-up, social vulnerabilities still strongly influence HIV-infected patients' interactions with the health care system. Day-to-day experience with the disease, including perceived treatment side effects, appears to play a key role in the quality of these interactions. More attention should be given to patient satisfaction, especially for socially vulnerable patients, in order to avoid potentially detrimental consequences such as poor adherence to ART.

Hepatitis C virus (HCV) protease variability and anti-HCV protease inhibitor resistance in HIV/HCV-coinfected patients.

OBJECTIVES: Data on the natural selection of isolates harbouring mutations within the NS3 protease, conferring resistance to hepatitis C virus (HCV) protease inhibitors (PIs), are limited for HIV/HCV-coinfected patients. The aim of this study was to describe the natural prevalence of mutations conferring resistance to HCV PIs in HIV/HCV-coinfected patients compared with HCV-monoinfected patients. METHODS: The natural prevalences of HCV PI resistance mutations in 120 sequences from HIV/HCV-coinfected patients (58 genotype 1a, 18 genotype 1b and 44 genotype 4) and 501 sequences from HCV-monoinfected patients (476 genotype 1 and 25 genotype 4), retrieved from GenBank as a control group, were compared. RESULTS: Of 76 sequences from HIV/HCV genotype 1-coinfected patients, six (7.9%) showed amino acid substitutions associated with HCV PI resistance (V36L, n=1; V36M, n=2; T54S, n=2; R155K, n=1). In 31 of 476 (6.5%) HCV genotype 1 sequences retrieved from the GenBank database, HCV PI resistance mutations were found. The difference was not statistically significant (P=0.6). All of the sequences from HIV/HCV genotype 4-coinfected patients and those retrieved from the GenBank database had amino acid changes at position 36 (V36L). CONCLUSION: Our study suggests that the natural prevalence of strains resistant to HCV PIs does not differ between HCV-monoinfected and HIV/HCV-coinfected patients. Further studies on larger cohorts are needed to confirm these findings and to evaluate the impact of these mutations in clinical practice.

[A case of severe community acquired pneumonia and non-respiratory illness induced by Influenza A]. / Une grippe exceptionnelle.

BACKGROUND: Severe community acquired pneumonia is a common cause of acute respiratory failure. The influenza virus itself can cause a severe pneumonia and non-respiratory illness. CASE REPORT: A physician developed an acute respiratory failure associated with hemolytic anemia, acute renal failure, and myocarditis. Influenza A infection was diagnosed by screening for antibodies (complement fixation, ELISA Ig A). DISCUSSION: Fulminant influenza pneumonia is a rare clinical presentation of influenza infection and usually has a severe clinical course. Influenza infection is also associated with myositis, myocarditis, acute renal failure, encephalopathy, and hemolytic anemia. Rapid laboratary diagnosis can be made by PCR or immunofluorescence applied directly to respiratory specimens. Antiviral treatment did not prove its efficacy in fulminant Influenza. This case report is an opportunity to stress the importance of seroprophylaxis by parenteral vaccination in exposed occupations.

HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation.

BACKGROUND: The K65R HIV-1 reverse transcriptase (RT) mutation is a multidrug resistance mutation which may be correlated with specific antiretroviral combinations and with the presence or absence of other RT resistance mutations. OBJECTIVES: The aims of this study were: (i) to determine the prevalence of the K65R mutation in a cohort of antiretroviral-treated patients; (ii) to study genotypic patterns and treatment characteristics in patients in whom the K65R mutation was present. STUDY DESIGN: We included in the study all antiretroviral-experienced patients followed up at the Bordeaux University Hospital in 2003 and 2004 for whom an HIV-1 genotypic resistance analysis was available. Information on RT resistance mutations was reported from a hospital database including therapeutic and biological parameters. The prevalence of K65R was investigated for all patients. Genotypic patterns and treatment characteristics were examined at the time of detection of the K65R mutation. RESULTS: The prevalence of K65R was 1.9% (26 of 1404 patients). K65R was associated with nucleoside RT inhibitor-based regimens in 22 patients, and with tenofovir disoproxil fumarate, lamivudine, didanosine and abacavir in 23, 17, 17 and eight patients, respectively. The M184V and Q151M mutations were the most commonly co-selected substitutions. Thymidine analogue mutations (TAMs) were rarely co-selected with K65R and inversely associated with K65R. CONCLUSION: The K65R mutation may emerge preferentially in the absence of zidovudine and TAMs, suggesting the possibility of an antagonistic interaction between K65 and TAMs.

[Clinical, microbiological, and therapeutic aspects of Nocardia sp. infections in the Bordeaux hospital from 1993 to 2003]. / Aspects cliniques, microbiologiques et thérapeutiques des infections à Nocardia sp. au centre hospitalier universitaire de Bordeaux entre 1993 et 2003.

OBJECTIVE: Our goal was to describe the epidemiological, clinical, and microbiological characteristics of nocardiosis in the Bordeaux teaching hospital, between January 1, 1993 and December 31, 2003. DESIGNS: The retrospective study included patients examined between January 1, 1993 and December 31, 2003 in whom a Nocardia bacterium had been identified from a biological sample. RESULTS: Twenty-four out of 30 Nocardia sp. strains identified during the study period were classified as colonizing strains. 19 patients presented with risk factors for nocardiosis. Nocardia asteroïdes were found in 22 samples, mainly from pulmonary samples. 11 cases of infection due to Nocardia sp. were reported during the study period. Immunosuppression was reported in 7 cases. The clinical forms were not specific. The species incriminated belonged to the N. asteroïdes complex in 8 cases. Treatment consisted in a combination of 2 or 3 molecules including cotrimoxazole for an average duration of 9 months. 9 patients recovered. CONCLUSIONS: The variability of clinical presentation and the lack of standard identification methods delayed the diagnostic. The treatment is not well defined. Clinical strains should be reported to the reference laboratory and prospective studies are necessary.

An imported case of canine rabies in Aquitaine: investigation and management of the contacts at risk, August 2004-March 2005.

In August 2004, a case of rabies was diagnosed in a puppy that had been illegally imported from Morocco to Bordeaux (France). Because a great number of people and animals were thought to have come into contact with the puppy, extensive tracing measures were implemented, and an international alert was launched to trace and treat the contacts at risk. One hundred and eighty seven people received post-exposure treatment, eight of whom also received serovaccination, and 57 animals known to have been exposed to the puppy were tested. Six months after the death of the rabid animal, none of the people treated showed any signs of rabies, nor was any secondary animal case reported. The management of this crisis highlights the importance of the role of a rapid alert system at European level. Strict application of sanitary control regulations is essential for animals introduced into EU countries, and all necessary information must be made available to EU residents travelling to rabies enzootic areas.

Carotid intima-media thickness is slightly increased over time in HIV-1-infected patients.

OBJECTIVES: HIV-infected patients are at risk of atherosclerosis and cardiovascular diseases. In a 12-month follow-up study, we aimed to investigate changes in carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis, and its determinants in HIV-1-infected patients. METHODS: Our multicentre prospective longitudinal cohort study included 346 HIV-infected patients, for each of whom two IMT measurements were taken by B-mode ultrasonography at baseline (M0) and 1 year later (M12). RESULTS: We observed a significant but moderate increase in the common carotid artery (CCA) median IMT, from 0.54 to 0.56 mm (P<10(-4)), i.e. an increase of 0.020 mm (95% confidence interval 0.012-0.029). There was a significant association between cross-sectional CCA IMT measures at M12 and conventional cardiovascular risk factors (higher CCA IMT with older age, P<10(-4); male gender, P=0.02; tobacco consumption, P=0.05), as well as higher CD4 cell count at M12 (>median 455 cells/microL, P=0.01). Only CD4 cell count at M0 was strongly and positively associated with the variation in IMT between M0 and M12 (P=4 x 10(-3)). IMT progression was +0.0020 mm for the lowest quartile of CD4 cell count distribution at M0, i.e. 3-253 cells/microL, +0.010 mm for 253-402 cells/microL, +0.043 mm for 402-590 cells/microL, and +0.028 mm for 590-2270 cells/microL. No association was found with type or duration of antiretroviral exposure. CONCLUSIONS: Conventional cardiovascular risk factors are major determinants of IMT evolution. The link between immunological status and carotid IMT requires further study.

An imported case of canine rabies in Aquitaine: Investigation and management of the contacts at risk, August 2004-March 2005.

In August 2004, a case of rabies was diagnosed in a puppy that had been illegally imported from Morocco to Bordeaux (France). Because a great number of people and animals were thought to have come into contact with the puppy, extensive tracing measures were implemented, and an international alert was launched to trace and treat the contacts at risk. One hundred and eighty seven people received post-exposure treatment, eight of whom also received serovaccination, and 57 animals known to have been exposed to the puppy were tested. Six months after the death of the rabid animal, none of the people treated showed any signs of rabies, nor was any secondary animal case reported. The management of this crisis highlights the importance of the role of a rapid alert system at European level. Strict application of sanitary control regulations is essential for animals introduced into EU countries, and all necessary information must be made available to EU residents travelling to rabies enzootic areas.

Symptomatic bone disorders in HIV-infected patients: incidence in the Aquitaine cohort (1999-2002).

BACKGROUND: Since the inception of highly active antiretroviral therapy (HAART), mortality among HIV-infected patients has decreased, but this has been accompanied by the appearance of several complications. OBJECTIVES: To estimate the incidence of symptomatic bone disorders in HIV-infected patients of the Aquitaine cohort (from south-west France) for the period 1999-2002, and to describe cases. METHODS: We retrospectively studied the records of 2700 patients of the Aquitaine cohort, which was derived from a hospital-based surveillance system of HIV infection in France. All cases of symptomatic bone disorders diagnosed from 1 January 1999 to 30 June 2002 were reviewed. RESULTS: Fourteen cases of bone disorders were diagnosed, eight cases of aseptic osteonecrosis and six cases of severe osteoporosis, representing incidences of 0.3/1000 patient-years [95% confidence interval (CI): 0.14-0.62] and 0.22/1000 patient-years (95% CI: 0.09-0.52), respectively. All patients with aseptic osteonecrosis were male, while all but one with osteoporosis were female. The ages of patients ranged from 36 to 54 years for osteonecrosis and from 39 to 50 for severe osteoporosis. At the time of clinical diagnosis, all patients were treated with nucleoside reverse transcriptase inhibitors (duration of treatment ranging from 19 to 123 months for osteonecrosis and from 46 to 132 months for severe osteoporosis). Ten patients were treated with nonnucleoside reverse transcriptase inhibitors [duration of treatment ranging from 6 to 31 months for osteonecrosis (n=6) and from 4 to 29 months for severe osteoporosis (n=4)]. Thirteen patients were treated with protease inhibitors [duration of treatment ranging from 12 to 62 months for osteonecrosis (n=8) and from 3 to 44 months for severe osteoporosis (n=5)]. All osteonecrosis and five osteoporosis patients had at least one known risk factor or comorbidity associated with the bone disorder occurrence. CONCLUSIONS: In our study, the aetiology of clinical bone disorders seemed to be multifactorial, as almost all the patients had at least one possible risk factor in addition to HAART exposure.

Emphysematous cystitis.

We present a case of emphysematous cystitis in a diabetic patient with a poor glycemic control in the context of alcoholic chronic pancreatitis. A 62-year-old woman was admitted to the emergency department after being found on floor with confusion and vomiting. The clinical examination was unremarkable except she was undernourished, agitated and presented an hepatomegaly. Urine contained 5.104 leukocytes/mm3 and culture grew Escherichia coli, 10(7) Colony Forming Unit/ml. Abdominal plain film showed gas shadows along the wall of urinary bladder. CT scan of the pelvis confirmed the presence of gas, and diffuse thickening of the urinary bladder wall. A Foley catheter was placed and the patient was treated with antibiotics for 6 weeks. She was also treated with insulin, rehydratation, vitamin B1 and B6, and pancreatic enzyme replacement. Emphysematous cystitis is defined by the presence of gas in the urinary bladder wall. It complicates urinary tract infections especially in diabetic patients but other disabled general medical conditions may be present. Because this relatively uncommon disease may present with fairly nonspecific findings, the diagnosis is often made incidentally on X-rays. However, as early diagnosis and treatment improve the outcome, a high index of suspicion for unusual presentations is warranted. Every diabetic patient with a urinary tract infection who seems to be severely ill should have an abdominal X-ray as a minimal screening tool to detect emphysematous complications.

Isolated antibodies against the core antigen of hepatitis B virus in HIV-infected patients.

The aim of this study was to describe the frequency and significance of isolated antibodies against the hepatitis B virus (HBV) core antigen (HBc) in 2185 HIV-infected patients of the Aquitaine Cohort. Antibodies against HBc were found in 372 subjects (17%). Patients with isolated anti-HBc antibodies were more frequently coinfected with hepatitis C virus (HCV) (58.2%) than those who were anti-HB surface (HBs) antibody positive (22.9%, P<0.001) and those who were dually reactive anti-HBs/anti-HBc antibody positive (27.3%, P<0.001). These results suggest interactions between HBV and HCV. As observed in patients not infected with HIV, the "anti-HBc-alone" serological profile could reflect essentially late immunity with undetectable anti-HBs antibodies. However, an occult HBV infection cannot be ruled out.

Cold bone defect on granulocytes labelled with technetium-99m-HMPAO scintigraphy: significance and usefulness for diagnosis and follow-up of osteoarticular infections.

We wished to determine the frequency and significance of cold bone defect on granulocytes labelled with technetium-99-m-hexamethylpropyleneamine oxime (99mTc-HMPAO-PMN) in non-spinal bone infection. Cold bone defect was investigated as part of a retrospective review during a 2-y period. Patients who had possible osteoarticular infection underwent bone scintigraphy combined with 99mTc-HMPAO-PMN for diagnosis and follow-up. Osteomyelitis was confirmed by isolation of the responsible pathogen. Among 210 patients who had possible infection, 17 (8%) demonstrated a cold bone defect. The site of cold bone defect was for all patients the hip. All 17 patients had proven bacterial orthopaedic hardware-related infection. The single causative micro-organism was staphylococcus. Whatever the outcome, cold bone defect was constant regardless of follow-up equal to or longer than 18 months. These data suggest that this uncommon scintigraphic pattern is an indication of an infectious process similar to increased uptake.

[Menstrual staphylococcal toxic shock is still a reality]. / Le choc toxique staphylococcique menstruel est toujours d'actualité.

INTRODUCTION: Staphylococcal toxic shock replies to precise clinical-biological criteria; but can be difficult to diagnose. Today, the nonmenstrual form of shock is the most frequent. The incidence of menstrual shock is low but their potential severity must be recalled. OBSERVATIONS: A young 14 year-old girl and a 33 year-old woman presented with menstrual shock that was treated successfully. A relapse in the form of staphylococcal scarlet fever occurred in the second patient. In both cases, the strain Staphylococcus aureus, which produces the TSST-1 toxin, had been identified. CONCLUSION: The possibility of the occurrence of a menstrual staphylococcal shock in the year 2002 must be known. The polymorphism of the clinical and biological manifestations must be underlined. The search for a toxin can be conducted in an appropriate centre.

T-lymphocyte populations in hepatitis C and HIV co-infected patients treated with interferon-alfa-2a and ribavirin.

OBJECTIVE: The effects on T-lymphocyte populations of two interferon-alfa-2a (IFN) regimens associated with ribavirin were evaluated in 36 HCV-HIV co-infected patients with chronic hepatitis C, T-CD4 cell count > 250 cells/ micro L and a plasma viral load of < 10 000 HIV RNA copies/mL. METHODS: Patients were given IFN for 48 weeks. Group A (18 patients) received 6 mega units (MU) subcutaneously three times a week for 24 weeks, then 3 MU three times a week for the last 24 weeks. Group B (18 patients) received 9 MU daily for 2 weeks, 3 MU daily for 22 weeks, then 3 MU three times a week for the last 24 weeks. Serum HCV RNA was evaluated at weeks 12 and 72. Ribavirin was added at week 16 for virologic nonresponders at week 12. CD3, CD3 CD4, CD3 CD8, CD3 CD4 human leucocyte antigen (HLA)-DR and CD3 CD8 HLA-DR lymphocyte subsets were evaluated before, during and after treatment by cytofluorometry. Controls were healthy and HCV mono-infected patients. RESULTS: CD3 CD4 and CD3 CD8 T-cells counts were both impaired during anti-HCV therapy, but returned to baseline value after treatment completion. Lymphopenia concerned mainly CD8 T-cells, the percentage of which decreased, whereas that of CD4 increased. Three patients displayed reversible CD4 lymphopenia < 200 cells/ micro L. HIV infection at inclusion was responsible for higher CD3 CD8 HLA-DR T-cell percentages in co-infected patients than in healthy and HCV mono-infected subjects. T-cell sequestration in lymphoid tissues and enhanced apoptosis may account for lymphopenia. CONCLUSION: High-dosed IFN anti-HCV therapy induced only moderate and transient CD4 lymphopenia in HIV co-infected patients.

Intrahepatic HCV RNA loads in 37 HIV-HCV co-infected patients with controlled HIV infection.

Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co-infected patients with controlled human immunodeficiency virus (HIV) infection and correlated with clinical, biological, and histological parameters. Thirty-seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A) and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had HIV plasma loads < 10,000 copies/ml, CD4(+) count > 250/microl. All the patients but two were receiving antiretroviral treatment. Liver tissue and sera were used for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had serum and liver HCV RNA, and both levels were correlated (r = 0.47; P = 0.003). Intrahepatic HCV load did not depend on age, sex, duration of HCV infection, CD4(+), HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV load (r = 0.52; P = 0.001). Patients with METAVIR A1/A2 had significantly lower levels of liver HCV-RNA than were found in patients with METAVIR A3 (P = 0.026). Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)-treated patients had significantly lower intrahepatic HCV load (P = 0.04). A weak but significant correlation between serum and liver HCV RNA was found. The amount of hepatic HCV RNA was correlated with AST levels, histological activity, but not with HCV genotype or fibrosis. The immune improvement associated with PI regimens could help reduce HCV load, supporting a protective effect of PI-induced immune restoration.

Mechanism of virologic failure after substitution of a protease inhibitor by nevirapine in patients with suppressed plasma HIV-1 RNA.

A prospective study was set up to evaluate the emergence of HIV-1 resistance after a switch from an effective protease inhibitor (PI)-containing regimen to a multitherapy regimen including nevirapine (NVP). After 6 months with an undetectable viral load under a PI-containing regimen, the patients were switched to NVP with conservation of the associated nucleoside reverse transcriptase inhibitors (NRTIs). Patients were followed-up at 1 month and then every 3 months after switching therapy. Nucleotide sequence analysis of the pol gene was performed at the first points of virologic failure. Thirty-four patients were included. The NRTI-naive group (22 patients) had begun antiretroviral therapy with a PI-containing regimen, whereas 12 patients (experienced group) had been previously treated by nucleoside mono-and/or dual therapy. After a median follow-up of 40 weeks, no patient of the naive group, versus 41% of the experienced group, developed a virologic failure after the change toward NVP ( p =.003). The virologic failures were associated with the appearance of NNRTI-resistant mutations. All rebound mutants also presented NRTI-resistance mutations. These results are consistent with a higher risk of virologic failure after a switch to an NNRTI in patients with prior suboptimal treatment and suggest the hypothesis that archived resistant viruses may facilitate the emergence of NNRTI resistance.

[Ecthyma gangrenosum caused by Pseudomonas aeruginosa without septicemia in a neutropenic patient]. / Ecthyma gangréneux à Pseudomonas aeruginosa sans septicémie chez une patiente neutropénique.

INTRODUCTION: Ecthyma gangrenosum is a rare skin infection caused by gram negative bacteria. It involves immunocompromised patients, especially neutropenic patients, and can be easily diagnosed. EXEGESIS: We report a case of ecthyma gangrenosum without septicemia due to Pseudomonas aeruginosa in a myelodysplastic patient with severe neutropenia. Granulocyte growth factors adjunction was necessary in combination to antibiotics to obtain complete healing. CONCLUSION: In neutropenic patient, ecthyma gangrenosum due to Pseudomonas aeruginosa should be rapidly diagnosed to avoid septicemic complications. In the case of antibiotic treatment failure, granulocyte growth factors may be added. Frequent Pseudomonas aeruginosa infections justify bacteriologic survey to look for hospital contamination.

Impact of protease inhibitors on intrahepatic hepatitis C virus viral load.

During chronic hepatitis C, hepatitis C virus (HCV) load in plasma was shown to be higher in HIV-co-infected than in immunocompetent patients [1]. The reason for this increased HCV replication is not known. It may be as a result of HIV-induced immune deficiency [2], although some authors did not find any correlation with the CD4 cell count [3]. A direct interaction between HCV and HIV was also hypothesized [4]. Protease inhibitors (PI) used in highly active antiretroviral therapy (HAART) have no HCV reduction effect during the first months of treatment [5-8]. However, a decrease in HCV plasma load was recently described in patients treated with HAART for a year [9,10]. We therefore investigated the potential impact of HAART on intrahepatic HCV load.