Short duration of post-amputation antibiotic therapy in diabetic foot patients with total resection of osteomyelitis.

BACKGROUND: Short duration of post-amputation antibiotic therapy (2-5 days) is recommended in patients with diabetic foot osteomyelitis after total resection of infected bone tissue. OBJECTIVE: To evaluate the long-term effectiveness of short-duration post-amputation antibiotic therapy in diabetic patients with total resection of osteomyelitis assessed by sterile bone bacteriological samples obtained from the resection margin. METHODS: The endpoint was the absence of osteomyelitis relapse at 6 months, defined as recurrence of osteomyelitis with the need for surgical revision and/or new bone antibiotic therapy. RESULTS: Among 15 patients included, 12 (80%) were cured without recurrence of osteomyelitis at 6 months, with a mean duration of antibiotic therapy of 8.3±5.9 days post surgery. This result is comparable to literature data, while all of them reported longer duration of antibiotic therapy and/or shorter follow-up. CONCLUSION: Short duration of post-amputation antibiotic therapy in diabetic patients with sterile bacteriological samples obtained from resection margin seems effective.

Progressive multifocal leukoencephalopathy despite immune recovery in a HIV/HCV co-infected patient.

In HIV patients, HCV co-infection has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML). Furthermore, PML has also been described in patients with cirrhosis, whether related to HCV infection or not. We describe here the case of a HIV/HCV co-infected patient with cirrhosis who developed PML despite HIV suppression and CD4 cell count above 250/mm3 for 2 years. Immunological studies performed at onset of PML and before HCV therapy showed a decrease in naïve CD4 cells (CD45RA+CCR7+CD27+ CD4+ T cells - 23% cells, i.e. 75/mm3) and NK lymphopenia with abnormal and activated NK cells (CD3- CD16+ and/or CD56+) (5% lymphocytes, i.e. 58/mm3, CD69 91%, NKp30 26%). This impaired immunity, possibly related to HIV infection, or HCV infection or cirrhosis, or a combination thereof, could have led to the development of PML.

Kaposi sarcoma among people living with HIV in the French DAT'AIDS cohort between 2010 and 2015.

BACKGROUND: Although antiretroviral therapy (ART) has reduced the risk of Kaposi sarcoma (KS), KS cases still occur in HIV-infected people. OBJECTIVE: To describe all KS cases observed between 2010 and 2015 in a country with high ART coverage. METHODS: Retrospective study using longitudinal data from 44 642 patients in the French Dat'AIDS multicenter cohort. Patients' characteristics were described at KS diagnosis according to ART exposure and to HIV-plasma viral load (HIV-pVL) (≤50 or >50) copies/mL. RESULTS: Among the 209 KS cases diagnosed during the study period, 33.2% occurred in ART naïve patients, 17.3% in ART-experienced patients and 49.5% in patients on ART, of whom 23% for more than 6 months. Among these patients, 24 (11.5%) had HIV-pVL ≤50 cp/mL, and 16 (66%) were treated with a boosted-PI-based regimen. The distribution of KS localization did not differ by ART status nor by year of diagnosis. LIMITATIONS: Data on human herpesvirus 8, treatment modalities for KS and response rate were not collected. CONCLUSION: Half of KS cases observed in the study period occurred in patients not on ART, reflecting the persistence of late HIV diagnosis. Factors associated with KS in patients on ART with HIV-pVL ≤50 cp/mL remain to be explored.

Which antiretrovirals should be prescribed as first-line treatments? Changes over the past 10 years in France.

OBJECTIVE: To describe the changes in first-line antiretroviral (ART) regimens in France between 2005 and 2015 and patients' characteristics related to the use of protease inhibitors in 2015. METHODS: We extracted all patients starting ART between 2005 and 2015 from a large prospective cohort. Regimens were classified as three nucleoside reverse transcriptase inhibitors (NRTI), or two NRTIs with a boosted protease inhibitor (bPI), with a non-nucleoside reverse transcriptase inhibitor (NNRTI), or with an INSTI. Patients' characteristics at the time of initiation were collected. A multinomial logit model was fitted to analyze characteristics related to the choice of regimen in 2015. RESULTS: We analyzed data from 15,897 patients. The proportion of patients starting with (i) a bPI decreased from 60% before 2014 to 38.1% in 2015; (ii) an NNRTI decreased from 30% to 17.8% in 2015; (iii) an INSTI gradually increased to 39.4% in 2015. In 2015, patients with an initial viral load ˃5 log copies/mL were less likely to receive NNRTI (OR=0.08) or INSTI regimens (OR=0.69) than bPIs. Patients with initial CD4+ T cell count ˂200/mm3 were less likely to receive an NNRTI (OR=0.28) or an INSTI regimen (OR=0.52) than a bPI. Women were less likely to receive an NNRTI (OR=0.79) or an INSTI regimen (OR=0.71) than a bPI; although this depended on age. CONCLUSION: The use of bPI as first-line ART declined sharply in France from 2005 to 2015. bPI remained of preferential use in patients with high viral load, low CD4+ T cell count, and in women.

Risk of diabetes in HIV-infected patients is associated with cirrhosis but not with chronic HCV coinfection in a French nationwide HIV cohort.

BACKGROUND: Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections have been reportedly associated with a higher risk of diabetes mellitus (DM) but results are conflicting. AIMS: To determine whether there is an association between chronic HCV and the incidence of DM, and to study the role of factors such as cirrhosis, IFN-based HCV therapy, sustained virologic response (SVR) and chronic HBV infection among patients living with HIV (PLHIV) followed in a large French multicentre cohort in the combination antiretroviral therapy (cART) era. METHODS: All PLHIV followed up in the Dat'AIDS cohort were eligible. Cox models for survival analysis were used to study the time to occurrence of DM. RESULTS: Among 28 699 PLHIV, 4004 patients had chronic HCV infection. The mean duration of HCV follow-up was 12.5 ± 8.1 years. The rate ratio of DM was 2.74 per 1000 person-years. By multivariate analysis, increasing age, body mass index>25, AIDS status, nadir CD4 cell count ≤200/mm3 , detectable HIV viral load and cirrhosis (HR 2.26 95% CI 1.14-1.18; P < 0.0001) were predictors of DM, whereas longer cART duration was associated with a lower risk of DM. Chronic HCV and HBV infection and IFN-based HCV therapy were not associated with DM. In a subanalysis among HCV-infected patients, SVR was not related to DM. CONCLUSIONS: Our study shows that in the HIV population, cirrhosis is associated with an increased occurrence of DM, but not chronic HCV infection or duration of HCV infection.

Amoxicillin-tolerant Pasteurella multocida strain isolated from chronic dermohypodermitis after suboptimal exposure to amoxicillin is not associated with reduced growth rate.

Pasteurella multocida is rarely observed in human chronic infections. A Pasteurella multocida strain was isolated from a skin biopsy of chronic dermohypodermitis in a 21-year-old woman without an immunocompromised state. As this strain was viable one month after a cat scratch despite treatment by amoxicillin-clavulanic acid, we compared this strain's growth rate, amoxicillin Minimal Inhibitory and Bactericidal Concentrations (MIC and MBC), resistance to serum and ability to activate neutrophil granulocytes with those of control strains isolated during acute infections in humans without previous antibiotics exposure. This particular strain was not more resistant to serum and did not induce a lower phagocytic activity than control strains. It did not grow more slowly than control strains even after suboptimal exposure to amoxicillin. This particular strain was tolerant to amoxicillin but tolerance did not appear sufficient alone for the induction of a chronic infection in a host without an immunocompromised state.

Ageing with HIV: do comorbidities and polymedication drive treatment optimization?

OBJECTIVES: The aim of the study was to describe the ageing HIV-infected population (> 50 years old) and their current antiretroviral therapy (ART), comorbidities and coprescriptions in France in 2013 and to compare them to the younger population. METHODS: A retrospective analysis of a prospectively collected database was performed. The characteristics of patients receiving ART as well as their current ART and their numbers of comorbidities and comedications at the censoring date (1 July 2013) were compared between patients ageing with HIV infection, patients who seroconverted while ageing, and younger patients. RESULTS: We compared 10 318 ageing patients [median age 56 years; 25% interquartile range (IQR) 53-62 years] with 13 302 younger patients (median age 42 years; 25% IQR 36-47 years). The ageing patients were more frequently male than the younger patients (77 vs. 65%). Among the ageing patients, 7025 were diagnosed with HIV infection before 2000 and represented a distinct group, the 'experienced ageing' group, by comparison with the 'recently diagnosed ageing' group. Triple therapy containing a boosted protease inhibitor was used in 28.2% of the patients (vs. 39% and 36% of the younger and "recently diagnosed ageing" groups, respectively); a nonnucleoside reverse transcriptase inhibitor in 27% (vs. 33% and 38%, respectively), an integrase strand transfer inhibitor (INSTI) in 9% (vs. 7% and 9%, respectively), and another regimen (fewer or more than three drugs) in 35.8% (vs. 21% and 16.5%, respectively). "Experienced ageing" patients typically had one or more comorbidities (62.1%) and were receiving at least one comedication (71%). Central nervous system (CNS) agents (prescribed in 44.6% of the "experienced ageing" patients) and antilipidaemics (in 44.2%) were the most frequently prescribed comedications. INSTIs were used in 23% of the population and were used significantly more often in patients with comorbidities and coprescriptions. For all comparisons, P < 0.0001. CONCLUSIONS: In ageing HIV-infected patients, especially those with a long history of HIV infection, comorbidities and coprescriptions are highly prevalent.

Impact of Age-related Comorbidities on Five-year Overall Mortality among Elderly HIV-Infected Patients in the Late HAART Era--Role of Chronic Renal Disease.

OBJECTIVES: To identify main prognostic factors for 5-year mortality among age-related comorbidities (ARCs) in older people living with HIV (PLHIV). DESIGN: A prospective, multicentre cohort study with a 5-year follow-up period in the late HAART era (from January 2008 to December 2012). SETTING: The Dat'AIDS cohort involving 12 French hospitals. PARTICIPANTS: All actively followed HIV-1 infected patients aged 60 or older. MEASUREMENTS: The study endpoint was all-cause five-year mortality. The following ARCs were considered: chronic renal disease, cardiovascular diseases, cancer, chronic pulmonary disease, cirrhosis, diabetes and nutritional status. Hepatitis C (HCV), hepatitis B (HBV) co-infection and sociodemographic characteristics were also evaluated. Cox's Proportional Hazards model was used for multivariate analysis. RESULTS: Among 1415 PLHIV aged 60 or more patients included, mean age was 66±5.5 years; 154 died (mortality rate 2.47/100 patient-years). The most prevalent ARCs were chronic renal disease (20.1%), diabetes (14.2%) and cardiovascular diseases (12.2%). By multivariate analysis, chronic renal disease (adjusted hazard ratio (aHR)=2.25; 95% confidence interval (CI) [1.58-2.21]; p<10-4), cardiovascular diseases (aHR=2.40; 95%CI[1.64-3.52]; p<10-4), non-HIV related cancer (aHR=1.91; 95%CI[1.20-3.05]; p=0.007), cirrhosis (aHR=2.99; 95%CI[1.68-5.33]; p<10-3), HCV co-infection (aHR=2.00; 95%CI[1.18-3.38]; p=0.009), low body mass index (aHR=2.42; 95%CI[1.46-4.01]; p<10-3) and CD4 cell count < 200 cells/µl (aHR=2.23; 95%CI[1.36-3.65]; p=0.002) were independently associated with 5 year mortality. CONCLUSION: Due to a high prevalence, chronic renal disease and cardiovascular disease are main prognostic factors for 5-year mortality among aged PLHIV.

Liver stiffness values in HIV-infected patients with isolated anti-hepatitis B core antibodies.

BACKGROUND: Hepatitis B reactivation has been observed in HIV-infected patients with isolated anti-HBc. However, the impact of isolated anti-HBc on liver fibrosis is not known in this population. METHODS: We investigated liver stiffness values (LSV) in a population of HIV-infected patients with isolated anti-HBc, and attempted to identify risk factors for high values. RESULTS: Fifty-one out of 69 patients (74%) had low LSV (≤7.1 kPa). In univariate analysis, high LSV (>7.1 kPa) were associated with HCV coinfection, the duration of HIV infection, the duration of antiretroviral therapy and lipodystrophy. In age-adjusted multivariate analysis, HCV coinfection (OR 11.5; 95% CI, 3.0-62.9; P=0.001) and lipodystrophy (OR 4.6; 95% CI, 1.1-20.7; P=0.031) remained associated with high liver stiffness values. CONCLUSIONS: Lipodystrophy was the only factor associated with high liver stiffness values in our population of HIV-infected patients with isolated anti-Hbc and extensive exposure to antiretroviral drugs active on HBV, apart from HCV coinfection Our study correlates to recent studies the results of which have shown that lipodystrophy, and more generally mitochondrial toxicity, was associated with advanced liver fibrosis in HIV/HCV co-infected patients.

Factors associated with guideline-based hepatitis C virus (HCV) treatment initiation in HIV/HCV-coinfected patients: role of comorbidities and physicians' perceptions.

OBJECTIVES: Many HIV-infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti-HIV therapy. The aim of this study was to identify factors influencing guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients. METHODS: Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir score >F1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (<800000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow-up and those who did not. RESULTS: In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17-4.81; P=0.017], whereas patients with children (OR 0.53; 95% CI 0.30-0.91; P=0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01-0.78; P=0.03) were less likely to be treated. CONCLUSIONS: Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti-HCV therapy in this population.

Persistently normal alanine aminotransferase levels in HIV/HCV-coinfected patients: the role of steatosis.

OBJECTIVE: The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)-coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6-month period, in a group of 381 HIV/HCV-coinfected patients. METHODS: Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined. RESULTS: Thirty-six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28-0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20-0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15-6.68; P=0.023) were associated with persistently normal ALT levels. CONCLUSION: The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis.

Genital tract actinomycosis caused by Actimyces israëlii.

We report a case of actinomycosis caused by actinomyces israelii, related to the removal of intrauterine device (IUD). Diagnosing actinomycosis is difficult but should be considered in the event of any acute abdominal problems in a woman carrying an IUD. All abdominal organs may be affected. Even with a disseminated infection, the combination of appropriate antibiotic therapy (penicillin G) and surgery ensures a full recovery in most cases.

[Metastatic cancer of the prostate in a young 40 year-old HIV-infected male patient]. / Cancer de prostate métastatique chez un jeune adulte de 40 ans infecté par le VIH.

INTRODUCTION: Cancer of the prostate in HIV-infected patients has rarely been reported in the literature. OBSERVATION: A 40 year-old man presented with an adenocarcinoma of the prostate and bone and glandular metastases. The patient exhibited HIV seropositivity stage B1, the immune-virology of which was well controlled by antiretroviral tritherapy. COMMENTS: The relationship between cancer and HIV has been established for certain cancers such as Hodgkin's disease, non-Hodgkin malignant lymphoma, Kaposi's sarcoma and invasive cancers of the uterine neck in women. The significant increase in some cancers in patients infected by HIV (lung, penis, soft tissue, lips, seminoma) suggests the potential association with immunodepression unless it corresponds to a risk induced by antiretroviral treatments in the long term.

[Metastatic cancer of the prostate in a 40-year-old HIV-infected male patient]. / Cancer de prostate métastatique chez un jeune adulte de 40 ans infecté par le VIH.

INTRODUCTION: Cancer of the prostate in HIV-infected patients has rarely been reported in the literature. OBSERVATION: A 40-year-old man presented with an adenocarcinoma of the prostate and bone and glandular metastases. The patient exhibited HIV seropositivity stage B1, the immune-virology of which was well controlled by antiretroviral tritherapy. COMMENTS: The relationship between cancer and HIV has been established for certain cancers such as Hodgkin's disease, non-Hodgkin malignant lymphoma, Kaposi's sarcoma and invasive cancers of the uterine neck in women. The significant increase in some cancers in patients infected by HIV (lung, penis, soft tissue, lips, seminoma) suggests the potential association with immunodepression unless it corresponds to a risk induced by antiretroviral treatments in the long term.

[Hypoglycemia associated with pleural fibromas. Study of insulin-like growth factors (IGF) and pathogenic considerations]. / Hypoglycémie associée aux fibromes pleuraux. Etude des insulin-like growth factors (IGF) et considérations pathogéniques.

PURPOSE: Pathogeny of hypoglycemia associated with non-islet-cell tumors is unclear. We discuss the mechanisms of this syndrome. CURRENT KNOWLEDGE AND KEY POINTS: We report three cases of spontaneous hypoglycemia revealing pleural fibroma. Endocrine tests before surgery showed low serum growth hormone and insulin-like growth factor I (IGF-I), reduced serum IGF-II levels in two patient. Insulin-like growth factor binding protein-3 (IGFBP-3) was low and electrophoretic profile of IGF-II was the 'big IGF-II' type. We discuss the mechanisms of hypoglycemia associated with non-islet-cell tumor. Impaired formation of the ternary complexes and its consequences seem the main pathogenic factor. FUTURE PROSPECTS AND PROJECTS: Analysis of IGF and IGFBP and in situ measurements of IGF mRNA could help in understanding this syndrome and allow therapeutic considerations in the management of hypoglycemia by corticosteroids and growth hormone.