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Biomedical subjects

D Salmon-Céron

Publications and source records attributed to D Salmon-Céron.

At least 19 recordsLinked to original sources

Emergence of Legionella pneumophila pneumonia in patients receiving tumor necrosis factor-alpha antagonists.

BACKGROUND: Patients treated with tumor necrosis factor-alpha (TNF-alpha) antagonists have an increased risk of infection, but infection due to Legionella pneumophila has rarely been described in patients receiving such therapy. METHODS: A registry involving 486 clinical departments in France was designed by a multidisciplinary group (Recherche Axée sur la Tolérance des Biothérapies [RATIO]) to collect data on opportunistic and severe infections occurring in patients treated with TNF-alpha antagonists. All cases are reported to RATIO in accordance with national health authorities and validated by infectious disease experts. The legionellosis rate among patients treated with TNF-alpha antagonists was compared with the rate in France overall. RESULTS: We report a 1-year consecutive series of 10 cases of L. pneumophila pneumonia in France in 2004, including 6 cases treated with adalimumab, 2 treated with etanercept, and 2 treated with infliximab. The median patient age was 51 years (range, 40-69 years). Eight patients were treated for rheumatoid arthritis, 1 was treated for cutaneous psoriasis, and 1 was treated for pyoderma gangrenosum. The median duration of TNF-alpha antagonist treatment at onset of infection was 38.5 weeks (range, 3-73 weeks). Eight patients were receiving concomitant treatment with corticosteroids, and 6 were receiving treatment with methotrexate. The relative risk of legionellosis when receiving treatment with a TNF-alpha antagonist, compared with the relative risk in France overall, was estimated to be between 16.5 and 21.0. We also report a second episode of confirmed legionellosis following the reintroduction of infliximab therapy. CONCLUSIONS: L. pneumophila pneumonia is a potentially severe but curable infection that might complicate anti-TNF-alpha therapy. In patients receiving anti-TNF-alpha who develop pneumonia, legionellosis should be systematically investigated, and first-line antibiotic therapy should be efficient against L. pneumophila.

Adalimumab↗

[Management of cirrhosis complications in HIV patients coinfected with hepatitis B or C virus].

Cirrhosis is a serious complication of viral hepatitis, and its incidence is increasing in HIV patients coinfected with HCV or HBV as they live longer, thanks to effective antiretroviral treatment (Haart). HIV coinfection accelerates the progression of fibrosis in hepatitis. To implement preventive measures, prompt diagnosis of cirrhosis is important, either by liver biopsy or the noninvasive tests for fibrosis now under wide study (FibroTest, FibroScan, etc.). Afterwards, assessment of the severity of cirrhosis and screening for complications are both necessary: testing for liver failure (Child-Pugh and MELD scores), portal hypertension (upper gastrointestinal endoscopy), and hepatocellular carcinoma (ultrasound and alpha fetoprotein assay). Careful consideration of drug prescriptions and possible interactions is essential. Specific treatment for hepatitis B or C virus is possible at this stage of cirrhosis, although more difficult, especially for HCV (results influenced by genotype, additional risk of complications by lactic acidosis or hepatic decompensation). Management of the complications of portal hypertension must be planned, as for those without HIV infection. Treatment of hepatocellular carcinoma is still disappointing, and liver transplantation, although possible in these patients, must be evaluated.

Antiviral Agents↗

[Prevalence and risk factors of hepatitis A infection in an HIV-infected French population].

BACKGROUND: There are common risk factors between hepatitis A virus (HAV) and human immuno deficiency virus (HIV) infections. OBJECTIVES: We tried to evaluate if HIV-infected patients could be at risk for HAV. More over, HAV could worsen prognosis of HIV infection and HAV vaccination was then to be considered. Thus we assessed the prevalence and risk factors of HAV infection in an HIV-infected population. PATIENTS AND METHODS: Seroprevalence and risk factors for HAV were studied among 154 HIV-positive patients followed in a Parisian hospital (mean age: 42 years, male patients: 70.8%, female patients: 29.2%). They were screened for HAV antibodies and answered a questionnaire on risk factors for HAV and means of HIV contamination. RESULTS: The global prevalence was 72.7% [IC95%: 65.7-79.7]. We excluded patients who were born in highly endemic areas where seroprevalence reached 60% [IC95%: 51.2-70]. The HAV seroprevalence was almost 100% in migrants from highly endemic countries and for those born before 1946. The multivariate analysis showed that risk factors were the geographic origin [OR=20.88; IC95%: 2.40-181], age [OR = 2.33; IC95%: 1.24-4.39], and hemophilia [OR = 13.78; IC95%: 1.34-141]. CONCLUSION: Our results suggest that a screening test for HAV antibodies should be performed before vaccination, especially in HIV-infected patients born after 1946 or in non-endemic countries.

Adult↗

[Bilateral amyotrophic neuralgia (Parsonage Turner syndrome) with HIV seroconversion].

We report a unusual case of neuralgic amyotrophy (NA) occurring during the seroconversion stage of an HIV infection. Combined with previously published cases, our observation suggests that NA associated with HIV could belong to the group of early multiplex mononeuritis. Neurologists should be aware of HIV infection when managing a patient with NA.

Adult↗

Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy.

HIV infection is associated with a high incidence of AIDS-related lymphomas (ARLs). Since the use of highly active antiretroviral therapy (HAART), the incidence of AIDS-defining illnesses has decreased, leading to a significant improvement in survival of HIV-infected patients. The consequences of HAART use on ARL are under debate. This study compared the incidence and the characteristics of ARL before and after the use of HAART in a large population of HIV-infected patients in the French Hospital Database on HIV (FHDH) and particularly in 3 centers including 145 patients with proven lymphoma. Within the FHDH, the incidence of systemic ARL has decreased between 1993-1994 and 1997-1998, from 86.0 per 10 000 to 42.9 per 10 000 person-years (P < 10(-30)). The incidence of primary brain lymphoma has also fallen dramatically between the periods, from 27.8 per 10 000 to 9.7 per 10 000 person-years (P < 10(-11)). The analysis of 145 cases of ARL in 3 hospitals showed that known HIV history was longer in the second period than in the first period among patients with systemic ARL (98 versus 75 months; P <.01). Patients had a higher number of CD4 cells at diagnosis during the second period (191 versus 63/microL, P = 10(-3)). Survival of patients with systemic ARL also increased between the periods (from 6 to 20 months; P =.004). Therefore, the profile of ARL has changed since the era of HAART, with a lower incidence of systemic and brain ARL. The prognosis of systemic ARL has improved.

Antiretroviral Therapy, Highly Active↗

Plasma cytomegalovirus DNA, pp65 antigenaemia and a low CD4 cell count remain risk factors for cytomegalovirus disease in patients receiving highly active antiretroviral therapy.

OBJECTIVE: To study the natural history and the current risk factors for cytomegalovirus (CMV) disease in the context of highly active antiretroviral therapy (HAART). SETTING: Prospective multicentre cohort in 15 university hospitals in France. METHODS: A group of 198 patients with CD4 cell count < 100 x 10(6) cells/l (or < 200 x 10(6) cells/l under HAART for at least 2 months), no previous CMV disease and CMV-positive serology were followed every 4 months clinically and for virological testing including HIV RNA and CMV blood markers (culture, pp65 antigenaemia, plasma CMV DNA and CMV late mRNA by the polymerase chain reaction). RESULTS: At inclusion, median CD4 was 77 x 10(6) cells/l (0-308) and 85% of the patients received protease inhibitors. The percentage of patients receiving HAART reached 99% at 12 months. After a follow-up of 23.6 months, the incidence of CMV disease was 3.2/100 patient-years [95% confidence interval (CI) 1.3-5.0]. In univariate Cox models, all the CMV markers, a CD4 cell count remaining < 75 x 10(6) cells/l and an HIV viral load > 100,000 copies/ml were predictive for CMV disease. The hazard ratios for CMV disease were 11 for blood culture; 14 and 70 for pp65 antigenaemia of > or = 1 and > or = 100 nuclei/200,000 cells, respectively; 35 for plasma CMV DNA; 6 for CMV mRNA; 29 for CD4 < 75 x 10(6) cells/l; and 12 for HIV RNA > 100,000 copies/ml. In a stepwise multivariate analysis, only three covariates were independently associated with the occurrence of a disease: plasma CMV DNA, pp65 antigenaemia > or = 100 nuclei/200,000 cells and a CD4 count < 75 x 10(6) cells/l. CONCLUSION: CMV blood markers and CD4 count < 75 x 10(6) cells/l remain risk factors for CMV disease in patients receiving HAART. Analysis of plasma CMV DNA by the polymerase chain reaction is a reproducible and standardized tool that could be used as a decision marker for initiating CMV pre-emptive therapy.

AIDS-Related Opportunistic Infections↗

IgG subclass distribution in serum and various mucosal fluids of HIV type 1-infected subjects.

We measured total IgG1, IgG2, IgG3, and IgG4 concentrations by ELISA in serum (S), total saliva (TS), cervicovaginal secretions (CVS), seminal secretions (SPE), and rectal secretions (RS) from either CDC II/III HIV-1-infected subjects or healthy volunteers. Human serum albumin was measured in parallel to calculate the relative coefficient of excretion (RCE). Levels of IgG1 and IgG3 directed against gp120 MN also were measured by ELISA in all samples, and the specific activity (SA) calculated. HIV-1-specific IgG2 and IgG4 were not compared, as total IgG2 and total IgG4 levels in HIV-1-infected subjects were found to be lower than in the healthy controls. Despite substantial interindividual variability, total IgG1 and IgG3 concentrations in all fluids were greater in the HIV-1-infected subjects than in the healthy controls. Calculations of RCE indicated predominantly a transudative origin for IgG subclasses in the different mucosal fluids, except for CVS, in which IgG1, IgG2, and IgG4 was produced locally. The transduction behavior of IgG3 in secretions appears to be different from that of other IgG subclasses. HIV-1-infected subjects were considered positive for IgG1 and IgG3 antibodies against gp120 MN if their antibody levels exceeded the maximum titer measured in the control group. Positive levels of anti-gp120 MN IgG1 were detected for 100% of HIV-1-infected individuals in S, CVS, and SPE, 97% in TS, and 75% in RS. Fewer subjects had positive levels of IgG3 to gp120 MN in their secretions (maximum 67% in CVS). Despite the low concentrations of total IgG3, mean SA values for IgG3 to gp120 MN were greater in secretions than in serum. No significant difference in the SA values for IgG1 to gp120 MN was observed between the different fluids. Only CVS had a local production of HIV-specific IgG1 Our results highlight the importance of an HIV-specific IgG1 and IgG3 immune response in mucosal fluids from HIV-1-infected subjects.

Adult↗

[Adherence to antiretroviral treatments with a protease inhibitor in HIV-infected patients].

OBJECTIVE: Long-term therapeutic success of powerful antiretroviral treatments dependent on patient adherence. This study was conducted to assess the difficulties HIV-infected patients with advanced-stage disease encounter in adhering to antiretroviral treatments with a protease inhibitor. PATIENTS AND METHODS: A prospective self-administered questionnaire survey was conducted at our outpatient clinic for 2 months. CD4 counts and HIV viral loads were also determined. RESULTS: Seventy-one percent of the study population which included 262 responded to the questionnaire. The survey was made a median 215 days after initiating the antiprotease treatment with indinavir (71% of the cases), ritonavir (13%), saquinavir (6%), or a combination of protease inhibitors (10%). At onset of antiprotease treatment, mean CD4 count was 171+/-150/mm(3) and mean HIV viral load was 75,000 copies/ml. The treatment was considered to be difficult to take by 43% of the patients; 66% stated they had forgotten to take their drugs at least once a month. It was most difficult to take the drugs prescribed for the afternoon. Shifts of 1 hour were observed in 58% of patients. Non-adherence was frequent (1 failure to take drugs per week), observed in 13% of patients. Most often, the patients stated they had forgotten to take their drugs because of occupational or relational difficulties (52%). Non-adherence increased with duration of treatment. The drug most often associated with non-adherence was indinavir (73%). Age and sex did not influence adherence. Mean RNA HIV serum level was lower than at onset of the antiprotease treatment in the most non-adherent patients. At the time of the questionnaire, there was no difference in serum RNA HIV level or in the percentage of patients with an undetectable level between non-adherent and adherent patients. CONCLUSION: This survey confirmed difficulties in adherence are frequent and worsen with time. No relationship was found between non-adherence and reduction in viral load, suggesting that a short-term effect of these very active drugs despite lack of perfect adherence. Other factors (pharmacology, sensitivity to antiretroviral drugs.) also play a major role in therapeutic success.

Adult↗

Comparison of the distribution of IgG and IgA antibodies in serum and various mucosal fluids of HIV type 1-infected subjects.

We compared IgG and IgA distribution in serum, three different salivary samples, two different rectal secretion samples, cervicovaginal secretions, and seminal secretions from asymptomatic CDC stage II/III HIV-1-infected subjects (n = 44) and from HIV-1-seronegative volunteers (n = 52). In-house ELISAs were used to measure total IgG and total IgA levels, as well as HIV-specific anti-gp120 MN and anti-p24 LAI IgG and IgA. Human serum albumin was titrated in parallel to calculate the relative coefficient of excretion (RCE). In spite of substantial interindividual variability, total IgG concentrations in all fluids were found to be significantly greater in the HIV-1-infected group than in the seronegative subjects. Calculation of RCE values revealed three different types of mucosal secretion: secretions with no local Ig production, such as sperm; secretions with local production of IgA and transudative origin of IgG, such as salivary and rectal samples; and secretions with local production of both IgG and IgA, such as in cervicovaginal secretions. For all mucosal specimens from HIV-1-infected subjects, the response to HIV-1 was predominantly IgG, with highest titers observed in cervicovaginal secretions (although these were lower than serum levels). In contrast, the specific IgA response appeared weaker in the mucosa than in serum.

Adult↗

Safety and immunogenicity of a live recombinant canarypox virus expressing HIV type 1 gp120 MN MN tm/gag/protease LAI (ALVAC-HIV, vCP205) followed by a p24E-V3 MN synthetic peptide (CLTB-36) administered in healthy volunteers at low risk for HIV infection. AGIS Group and L'Agence Nationale de Recherches sur Le Sida.

A live recombinant canarypox vector expressing HIV-1 gpl20 MN tm/gag/protease LAI (ALVAC-HIV, vCP205) alone or boosted by a p24E-V3 MN synthetic peptide (CLTB-36) was tested in healthy volunteers at low risk for HIV infection for their safety and immunogenicity. Both antigens were well tolerated. ALVAC-HIV (vCP205) induced low levels of neutralizing antibodies against HIV-1 MN in 33% of the volunteers. None of them had detectable neutralizing antibodies against a nonsyncytium-inducing HIV-1 clade B primary isolate (Bx08). After the fourth injection of vCP205, CTL activity was detected in 33% of the volunteers and was directed against Env, Gag, and Pol. This activity was mediated by both CD4+ and CD8+ lymphocytes. On the other hand, the CLTB-36 peptide was poorly immunogenic and induced no neutralizing antibodies or CTLs. Although the ALVAC-HIV (vCP205) and CLTB-36 prime-boost regimen was not optimal, further studies with ALVAC-HIV (vCP205) are warranted because of its clear induction of a cellular immune response and utility as a priming agent for other subunit antigens such as envelope glycoproteins, pseudoparticles, or new peptides.

AIDS Vaccines↗

Development and standardization of methods to evaluate the antibody response to an HIV-1 candidate vaccine in secretions and sera of seronegative vaccine recipients.

Enzyme-linked immunosorbent assays (ELISA) were developed to test, in serum and mucosal samples, total IgG, total IgA, serum albumin, and anti-gp120 MN and anti-p24 LAI IgG and IgA levels. These ELISAs were optimized according to reagents and experimental conditions. Inter- and intra-assay coefficients of variation ranged from 3.3% to 18.6%. The ELISA results were linear and precise, and for anti-HIV-1 IgG and IgA, the analytical recovery was close to 100%. For IgG and IgA titration against gp120 MN and p24 LAI, standards were made using pooled sera or gammaglobulins with assigned titres in ELISA units per ml (EU/ml). These standards were used to obtain a linear regression curve that could then be used to obtain the titres of experimental samples. The cut-offs for positivity were determined for sera and mucosal fluid using healthy controls. Validation conditions were defined for ELISAs, and samples that did not satisfy these conditions were retested. Measurement of total IgG and IgA allowed normalization and comparison of the results of specific immunoglobulin levels between different samples. Serum albumin was tested as a marker of transudation from serum to mucosal fluid, allowing calculation of the relative coefficient of excretion, which is one element required to determine the origin of the immunoglobulin detected in mucosal samples. These ELISAs were developed with samples from HIV-1-infected and healthy subjects. We now have the tools to study and understand mucosal immunity in seronegative subjects vaccinated with an HIV-1 candidate vaccine.

AIDS Vaccines↗

Effect of a 14-day course of foscarnet on cytomegalovirus (CMV) blood markers in a randomized study of human immunodeficiency virus-infected patients with persistent CMV viremia. Agence National de Recherche du SIDA 023 Study Group.

A randomized open-label phase 2 trial compared the virological and clinical effects on cytomegalovirus (CMV) infection of a 14-day course of intravenous foscarnet (100 mg/[kg x 12 h]) or no treatment in 42 HIV-infected patients with < 100 CD4 cells/mm3 and persistent asymptomatic CMV viremia. All CMV markers (blood culture, pp65 antigenemia, plasma and leukocyte DNA) either became negative or decreased significantly at day 14 in the foscarnet group. CMV blood culture results at day 14 were positive in 14% of those receiving foscarnet versus 60% of control patients (P = .004). However, after the end of treatment, all markers reappeared or the virus load rapidly increased. The probability of CMV disease at 6 months was 43% in both groups. Patients who had or who achieved a negative blood culture at any time had a reduced risk of CMV disease (RR = 2.64; 95% CI = 1.24-5.62; P = .02). This study suggests that sequential courses of intravenous foscarnet might not be a good strategy for preemptive therapy in this population and that in patients with a positive blood marker, treatment able to induce and maintain negative CMV blood cultures could constitute an effective intervention.

AIDS-Related Opportunistic Infections↗