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Biomedical subjects

J L Vildé

Publications and source records attributed to J L Vildé.

At least 19 recordsLinked to original sources

Salivary cytomegalovirus (CMV) shedding, glycoprotein B genotype distribution, and CMV disease in human immunodeficiency virus-seropositive patients.

To assess the frequency of shedding of cytomegalovirus (CMV) in saliva, the distribution of CMV glycoprotein B (gB) genotypes, and the occurrence of CMV diseases, we screened 98 human immunodeficiency virus (HIV)-seropositive patients without CMV disease. CMV was detected by culture more frequently in saliva (45 [46%] of 98 patients) than in blood (7 [7.5%] of 93) and was associated with CD4 cell counts <100 cells/mm3 (P=.013). CMV in the saliva of 37 patients was successfully genotyped. Three patients (8%) were infected by a gB1 strain, 26 (70%) by a gB2 strain, 2 (5.5%) by a gB3 strain, 1 (3%) by a gB4 strain, and 5 (13.5%) by mixed gB strains. Thirteen patients developed CMV disease after a mean period of 143+/-112 days; at inclusion, 9 (69%) had salivary CMV shedding and 2 had CMV viremia. CMV salivary shedding (P=.043), low CD4+ cell count (P=.041), and CMV viremia (P=.011) were associated with occurrence of CMV disease.

AIDS-Related Opportunistic Infections↗

[Paradoxical aggravation of tuberculosis after antiretroviral therapy in HIV-infected patients].

BACKGROUND: Restoration of immunocompetence in HIV-infected patients after antiretroviral treatment can have unexpected effects. CASE REPORTS: An unusual course of treated tuberculosis was observed in four HIV-infected patients soon after initiation of antiretroviral therapy. These patients developed fever and enlarged necrotic adenopathies despite an efficacious antituberculous therapy. They were in the initial stage of their antituberculous therapy that had been initiated a mean 12 days prior to initiation of antiretroviral therapy. The antiretroviral therapy led to an undetectable HIV load within 2 months. DISCUSSION: These unusual features, which also occurred with an increase in CD4 cell counts, could be related to the immunological restoration and to the reappearance of delayed type hypersensitivity. The onset of antiretroviral therapy could thus be delayed by several weeks in HIV-infected patients treated for active tuberculosis and who have never received antiretroviral therapy.

Antitubercular Agents↗

Possible mechanism of toxicity of zidovudine by induction of apoptosis of CD4+ and CD8+ T-cells in vivo.

Some HIV-infected patients have a discordant response to highly active antiretroviral therapy with a low virus load and an incomplete restoration of CD4+ T-cell counts. Zidovudine may limit CD4+ restoration by a hematotoxic mechanism. Apoptosis and T-cell counts were assessed in two patients before and after they switched from zidovudine to stavudine. Whereas CD4+ T-cell apoptosis fell from 52% and 66% before the zidovudine switch to 7% and 12%, respectively, after the switch, the patients' CD4+ counts rose gradually to +183 and +150 cells, respectively. It was therefore hypothesized that zidovudine directly induced apoptosis. Zidovudine withdrawal could be tested before immunological interventions such as interleukin-2 therapy are considered.

Anti-HIV Agents↗

Definite streptococcus bovis endocarditis: characteristics in 20 patients.

OBJECTIVE: To determine the specific characteristics of Streptococcus bovis infective endocarditis (IE) by reviewing our own experience of S. bovis IE. METHODS: Twenty episodes of definite S. bovis IE were reviewed in 20 patients hospitalized from 1980 to 1996. RESULTS: The mean age was 62 +/- 14 years, and 14 (70%) patients had no known predisposing cardiac condition. The principal antimicrobials used were penicillin G (N = 10) and amoxycillin (N = 8). Surgery was required in four (20%) patients. Neurologic complications occurred in eight (40%) patients, after initiation of therapy in six (75%) (mean time: 14 days). An unfavorable outcome was observed in four of 20 patients and tended to be more frequent in patients who had had neurologic complications (P = 0.10). Colonic tumors were present in 11 of 16 (69%) patients. CONCLUSIONS: Advanced age, occurrence of IE on presumably normal valves, high rate of neurologic complications, associated gastrointestinal diseases and low mortality rate during initial follow-up are characteristic features of S. bovis IE observed in this study.

Adult↗

[Skin manifestations of immune restoration syndrome in treated tuberculosis].

INTRODUCTION: Immune restoration syndrome was first described in 1998 and involved mycobacterium avium complex. We report the case of a patient with acquired immunodeficiency syndrome who had disseminated cutaneous lesions due to Mycobacterium tuberculosis, following initiation of highly active antiretroviral therapy. CASE REPORT: A 42 year-old HIV-infected man, was admitted for fever, cough, nocturnal sweat and impaired of general condition. He had a viral load of 127,200 copies/ml and 199/ml CD4 T-cells. He was treated with triple tuberculosis combination therapy according to tuberculous contagium, positivity of the tuberculin intradermoreaction (15 mm) and right upper lung nodule on thoracic scan. M. tuberculosis was not found. Fever improved at day 3. Highly active antiretroviral therapy with zidovudine, lamivudine, indinavir, was started at day 11 and 33 days after, fever and dermohypodermal nodules with necrotising evolution appeared. Skin biopsy specimen showed tuberculoid granuloma. The levels of viral load and CD4 T-cells were less than 200 copies/ml and 497/ml respectively. Fever and cutaneous lesions spontaneously resolved without changing therapy. DISCUSSION: Immune restoration syndrome appears after initiation of antiretroviral therapy, in patients with advanced HIV infection and without prophylactic treatment versus MAC. This case report probably involves mycobacterium tuberculosis. Bacterial lysis and immune restoration take part in cutaneous pathogenesis. Subclinical mycobacterial infection should be monitored during initiation of antiretroviral therapy in patients with advanced HIV infection.

Adult↗

Natural history of serum HIV-1 RNA levels in 330 patients with a known date of infection. The SEROCO Study Group.

OBJECTIVE: To describe the spontaneous course, before the introduction of highly active antiretroviral therapy (HAART), of HIV-1 RNA during the AIDS-free period of the disease. To assess the predictive value of changes in HIV-1 RNA levels. DESIGN: A total of 330 patients with a known date of infection followed in the SEROCO cohort. METHODS: HIV-1 RNA levels (threshold, 200 copies/ml) were evaluated from 2243 frozen sera obtained from enrolment until the onset of AIDS or until February 1996. Lowess curves were used to describe the variations of viraemia during follow-up. A Cox regression model was used to assess the predictive value of early and updated CD4 cell count and viral load. RESULTS: In addition to a lower early viral load, patients who remained AIDS-free had, on average, a longer period of viral load decrease after infection (36 versus 18 months), followed by a slower viral load increase compared with those who progressed to AIDS. A true plateau-phase after the seroconversion period, lasting approximately 4 years, was identified only in patients who remained AIDS-free for at least 90 months. In multivariate analysis, both early viral load and later changes were significant predictors of progression to AIDS. A decrease in the CD4 cell count to less than 200 cells/microl and the onset of a group B condition remained significant predictors of progression. CONCLUSION: Our study extends to the early post-seroconversion phase the prognostic value of extracellular HIV-1 RNA levels. Moreover, our data suggest that, in most HIV-infected individuals, a progressive loss of control of viral replication arises during the early years of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

High levels of IL-10 and determination of other cytokines and chemokines in HIV-associated haemophagocytic syndrome.

Haemophagocytic syndrome (HPS) and HIV infection are both associated with cytokine network dysregulation. We therefore analysed plasma levels and mRNA synthesis in peripheral blood mononuclear cells (PBMC) of cytokines, chemokines and chemokine receptors in one HIV-infected patient with HPS. We compared the results with those for eight HIV-infected patients with similar CD4+ T cell counts (207/mm3 versus controls: median 214/mm3) and plasma virus load (4.1 log copies/ml, versus controls: median 4.2 log copies/ml). The HPS patient had a lower viral DNA load in PBMC and higher plasma levels of interferon-gamma, IL-10, and macrophage inflammatory protein (MIP)-1beta. No difference in plasma tumour necrosis factor-alpha (TNF-alpha), IL-6 and MIP-1alpha concentration was observed between the HPS patient and control patients. No difference was observed in TNF-alpha, IL-1beta, IL-10, IL-4, MIP-1alpha, MIP-1beta, RANTES, CXCR-4, and CCR-5 mRNA levels in PBMC, but IL-6 levels were higher in the HPS patient. Our results emphasize the role of IL-10 in the control of immune hyperactivation that is observed in HPS.

Adult↗

Modalities of palliative care in hospitalized patients with advanced AIDS.

This prospective multidisciplinary survey started in October 1994. The survey assessed the modalities of care of hospitalized patients with advanced AIDS in an Infectious and Tropical Diseases Unit with regards to the practices of palliative care in a Palliative Care Unit. Seventy-eight (78) AIDS patients with CD4 < or = 30/mm3 who had 102 consecutive hospitalizations were recruited. Types (symptomatic or curative) and number of drugs administered to the patients, as well as biological and radiological investigations performed were recorded. Symptoms were concomitantly assessed on a weekly basis by self-evaluation of the patients themselves and by physicians. The results showed that the practices of care were different in the two units according to the specific goals and norms of each unit. A higher density of care was delivered at the Infectious and Tropical Diseases Unit. Symptoms assessed by both patients and physicians were underestimated by physicians in frequency and in intensity. In conclusion, an integrated approach including objective and subjective criteria should enable a better adjustment of the palliative and curative therapeutic strategies in advanced AIDS. These would concomitantly take into account the wishes of the patient and the goals regarding care in the unit where the patient is hospitalized.

AIDS-Related Opportunistic Infections↗

Use of corticosteroids in glomerulonephritis related to infective endocarditis: three cases and review.

We report the cases of three patients treated for infective endocarditis (IE) for whom corticosteroids were added to the antibiotic treatment. They all had clinical and biological evidence of immune-mediated glomerulonephritis. The microorganisms responsible for IE were Coxiella burnetii, Streptococcus bovis, and Cardiobacterium hominis. Median duration of IE before antimicrobial therapy was 7 months. In all patients, renal function deteriorated despite appropriate antimicrobial treatment for a mean duration of 16 days, but it improved after addition of corticosteroid therapy. All patients were cured of IE. A literature review revealed four additional cases of IE-related glomerulonephritis in which adjunctive immunosuppressive therapy was considered to be effective. Although corticosteroid therapy is generally not recommended for IE, it should be considered for patients whose renal dysfunction secondary to glomerulonephritis does not improve with appropriate antimicrobial treatment, especially if the duration of the illness is long.

Aged↗

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↗

Low rate of Clostridium difficile colonization in ambulatory and hospitalized HIV-infected patients in a hospital unit: a prospective survey.

OBJECTIVE: To determine the frequency of Clostridium difficile carriage in HIV-infected in- and out-patients, and to assess the role of this carriage in nosocomial transmission of C. difficile. PATIENTS AND METHODS: Prospective study in a university hospital. Forty-five consecutive HIV-infected out-patients and 120 hospitalized patients (52 HIV and 68 non HIV-infected-patients) were studied. During the period of hospitalization, 44 patients (24 HIV and 20 non-HIV-infected patients) with a negative culture within 48 h of admission were followed weekly for fecal carriage. Clostridium difficile culture and latex agglutination were performed on the fecal samples of each patient. In the case of positive culture and/or latex agglutination, C. difficile toxin assays were performed by microtitre cytotoxicity method. RESULTS: Out-patients: one patient was a carrier and one patient with diarrhoea was infected with a toxigenic strain (2/45, 4.5%, 95% CI = 1-17). Eighty percent of the HIV-infected out-patients had received antimicrobial agents previously. In-patients: in the first 48 h, five asymptomatic patients were carriers (three non-HIV and two HIV-infected patients). Among 20 patients who complained of diarrhoea, one HIV-infected patient had only a positive latex agglutination and one HIV-infected patient was infected with a toxigenic strain. Overall, 7/120 (5.8%, 95% CI = 2-10) patients were infected or colonized with C. difficile. During the hospitalization (743 patient-days), none of the 44 patients acquired C. difficile. CONCLUSION: This study suggests that in this given unit, C. difficile carriage is low, at least with single room accommodation, and in the absence of clusters of cases. This carriage is not different in HIV and non-HIV infected patients despite treatment with multiple antibiotics, and is not different in patients managed in different care environments. The systematic identification of C. difficile carriers for isolation and prophylactic treatment is not useful under these circumstances.

Ambulatory Care↗

Intention-to-treat vs. on-treatment analyses of clinical trial data: experience from a study of pyrimethamine in the primary prophylaxis of toxoplasmosis in HIV-infected patients. ANRS 005/ACTG 154 Trial Group.

Randomized clinical trials analyzed by the intent-to-treat approach provide unbiased comparisons among treatment groups. To avoid dilution of treatment effect, many people also perform an analysis by treatment actually received, although this method may introduce bias into the results. This paper presents several approaches used for analyzing data of a recent trial and the difficulties encountered in interpreting the results of each approach. The ANRS 005/ACTG 154 Study was a double-blind, placebo-controlled, randomized, international (French, U.S., and Spanish) multicenter trial designed to assess the effectiveness of pyrimethamine for the primary prophylaxis of cerebral toxoplasmosis (CT) in HIV-infected patients with advanced immunodeficiency. In the intention-to-treat analysis, the cumulative probability of CT at 1 year did not differ significantly between the pyrimethamine arm (11.9%) and the placebo arm (13.1%), Hazard Ratio (HR) = 0.94 (95% Confidence Interval (CI) = 0.62-1.42), whereas an on-treatment analysis resulted in a significant difference: 4.2% in the pyrimethamine arm and 12.4% in the placebo arm, HR = 0.44 (95% CI = 0.24-0.80). The data showed a significant interaction between compliance and treatment outcome; and side effects were more frequently cited as reasons for compliance violations in the pyrimethamine group. Several different analytic approaches (censoring data at the time patients discontinued the study medication only for selected reasons) failed to explain the disparity between the estimation of effect of pyrimethamine by the intention-to-treat and on-treatment analyses. This experience led us to believe that comparing the results of both analyses was the best method to convince clinicians that intention-to-treat was the only interpretable analysis. We were concerned that even if pyrimethamine had a beneficial effect, it was very difficult (1) to quantify and (2) to apply to clinical practice unless one could predict the occurrence of study drug discontinuation for each patient at the time of treatment assignment. Although exploratory analyses may yield clinically relevant information and useful clarifications in the evaluation of treatments, intention-to-treat remains the only interpretable analysis of clinical trials.

AIDS-Related Opportunistic Infections↗