Search

Objective: The characteristics of patients with a suspected SARS hospitalized in a Paris hospital were studied to analyze the hypothetic differences between epidemiologic and clinical teams in the management of an epidemic emerging disease, and to gather experience for the management of the next outbreak., Study Design: All 90 patients hospitalized between March 16 and April 30, 2003, were included. Epidemiological and clinical data were shared with the French National Institute for Health. Cases were classified according to both the official definition ("possible", "probable", "excluded") and a local one, adapted from the official definition but including an additional level of suspicion ("equivocal"), intermediate between "possible" and "excluded"., Results: The initial assessment was different in 39% of the cases (n=35), according to epidemiological (n=24) or clinical (n=11) elements. The final assessment diverged in 54% of the cases (n=47). All patients were officially considered as "excluded" for epidemiologists, while 47 remained as "possible" or "equivocal" cases of SARS according to the clinicians., Conclusion: The risk assessment was different in almost 40% of the cases, with no impact on epidemic diffusion or hospital-borne exposure as no probable case of SARS was diagnosed among these patients or their households. The confrontation of these different but complementary points of view will thus enrich the interdisciplinary management of eventual future outbreaks.

Objective: To describe the implementation and initial results of a specific educational and counseling intervention to examine and improve adherence to antiretroviral therapy (ARV) in HIV-infected patients., Method: Four patient profiles were defined: 1) discontinuation and 2) failure: patients with virological failure (defined as two consecutive viral loads>200 copies/mL) at ARV discontinuation or under treatment, both seen after the fact; 3) preparation: naive patients seen before starting treatment, and 4) reinforcement: patients in treatment seen for counseling to prevent virological failure. A clinical psychologist, nurse and hospital pharmacist jointly conducted the session. Data collected include standardized information about the characteristics of HIV infection and ARV regimens, and demographic, behavioral, social and cultural indicators. CD4 cell counts and HIV viral loads were recorded at D0, M1, M3, M9 and M12. The effectiveness of the adherence intervention was defined separately for each patient profile based on some combination of taking or restarting an ARV regimen, virological response, and M12 follow-up., Results: The study included 139 patients between November 1998 and April 2000. The intervention was defined as effective in 50% and 40% of the discontinuation (n=26) and failure (n=61) patients respectively, 84% of those with preparation profile (n=37) and 93% (14/15) of reinforcement patients. Only undetectable HIV viral load at M3 was significantly associated with the effectiveness of the adherence intervention for all 4 profiles. The preventive interventions (preparation and reinforcement) were less effective in patients from outside Europe (p=0.013)., Conclusion: The adherence intervention was more effective in preventing virological failure than in restoring ARV effectiveness among patients who had already experienced virological failure. It should therefore be proposed primarily before starting ARV, to prevent failure in treatment-naive patients, especially those from outside Europe.

Background: Efavirenz (EFV) is a highly active antiretroviral drug, use of which is associated with frequent (although transient) neurosensorial adverse reactions. Whether the use of EFV is associated with the risk of depression or suicide remains controversial., Methods: ALIZE-ANRS (Agence Nationale de Recherches sur le SIDA et les Hepatites Virales) 099 was a 48-week randomized trial involving virologically suppressed, human immunodeficiency virus (HIV)-infected patients that compared the maintenance of a treatment regimen that contained protease inhibitors (177 subjects) with a switch to a once-daily combination of EFV, didanosine, and emtricitabine (178 subjects). We used the trial's adverse events reporting system and a self-administered Center for Epidemiologic Studies-Depression Scale questionnaire to assess depressive disorders. Determinants were studied using a multivariate proportional hazards model adjusted for antiretroviral treatment, sex, age, HIV risk factor, history of depression, hepatic disorder, alcohol abuse, and HIV-related or non-HIV-related events., Results: Thirty cases of depressive disorder (26 cases of depression and 4 suicide attempts) occurred during treatment in 27 patients (12 patients [7%] and 15 patients [8%] in the protease inhibitor-based and EFV-based treatment arms, respectively; P = .56). In the proportional hazards model, only age (hazard ratio, 1.6 per 10 years younger; 95% confidence interval, 1.0-2.6) and a history of depressive disorder (hazard ratio, 5.0; 95% confidence interval, 2.1-12.0) were associated with a risk of depressive disorders. The proportion of depressive patients (24%), as determined on the basis of the Center for Epidemiologic Studies-Depression Scale data, was stable during the follow-up period, without difference between treatment groups. Patients with a history of depressive disorder were more frequently depressed (53%) than were those without such history (22%; P = .03)., Conclusions: The frequency of depressive disorders was high in this population, but the disorders were not related to EFV treatment. Younger age and a history of depression are important determinants for depression and should be considered for early detection and case management.

Diffuse infiltrative lymphocytosis syndrome (DILS) in patients with human immunodeficiency virus (HIV) infection is characterized by persistent CD8(+) lymphocytosis with visceral lymphocytic infiltration. DILS induces a large spectrum of clinical features. We describe 2 HIV-infected patients with upper respiratory tract involvement that occurred during the course of DILS.

Background: Kaposi's sarcoma (KS) is a potentially life-threatening multifocal neoplasm. Despite the significant decline in the incidence of acquired immune deficiency syndrome (AIDS)-related KS with the use of highly active antiretroviral therapy (HAART), some patients, even those with a good immune restoration, still have aggressive disease. Liposomal anthracyclines or combination chemotherapy are widely used but adverse effects limit their utilization., Objectives: We studied the efficacy and tolerance of docetaxel in the treatment of AIDS-related KS after pretreatment with anthracycline. PATIENTS/METHODS AND MAIN OUTCOME MEASURE: A retrospective cohort study was done. Nine human immunodeficiency virus (HIV)-infected patients were treated from 1997 to 2002 with docetaxel. Tumour response was evaluated using the AIDS Clinical Trial Group (ACTG) staging criteria. Clinical and biological toxicity was evaluated. AIDS status with HIV viral load and CD4 T-cell count were measured at the beginning and at the end of the treatment., Results: A major (complete or partial) response and a stabilization of the disease were demonstrated in seven and two patients, respectively. Grade 4 neutropenia and thrombocytopenia were observed in four of nine and one of nine patients, respectively. One patient died after sepsis., Conclusions: Docetaxel has a good and rapid efficacy in anthracycline-pretreated patients with severe AIDS-related KS. Phase II/III trials should be done to compare docetaxel with liposomal anthracyclines as a first-line treatment.

Objective: Schizophrenia might appear to be an obstacle to the initiation of and especially compliance with antiretroviral therapy for HIV-infected patients. The aims of this study were to describe the clinical, immunologic and virologic course after initiation of antiretroviral therapy in 7 HIV patients with schizophrenia (according to DSM-IV-R criteria), and to analyse the possibilities of an adequate antiretroviral therapy for those patients., Observations: Multidisciplinary management by specialists in infectious diseases, addiction-related disorders, treatment adherence and compliance, and psychiatrists, as well as social workers, home care agencies, and patient advocacy and assistance groups, was organized with coordinated medical-psychiatric follow-up at least once a month. The patients, 6 men and 1 woman, were aged from 26 to 48 years; schizophrenia had been diagnosed in 5 patients 6 months to 20 years before the HIV infection was discovered; diagnoses of both diseases were essentially simultaneous for the other 2. All patients took long-term neuroleptics for their schizophrenia. Two were active drug addicts who received drug substitution treatment. Before antiretroviral treatment began, 6 patients had advanced infection: stage C with peak CD4 cell counts ranging from 6 to 70/mm3; they began treatment with protease inhibitors between May 1996 and August 1997. The seventh patient was first seen during primary HIV infection in July 1998, and treatment began then. Response to antiretroviral treatment with protease inhibitors was slow for all patients, but viral load became undetectable for 6 of the 7, after 5 months to 4 years; 3 had opportunistic infections. Follow-up ended in January 2002: 5 patients still had undetectable viral loads,, with CD4 cell counts ranging from 45 to 1 000/mm3. One patient died from mixed terminal cirrhosis (alcohol abuse and hepatitis C); the viral load in another was only partially controlled (10 000 copies/ml), because of poor treatment adherence., Conclusion: Individuals with schizophrenia can respond well to antiretroviral treatment, although response may appear slow; they can adhere to complex treatment regimens as long as they receive well coordinated and sustained multidisciplinary support.

Introduction: Tuberculosis can be responsible for myocardial damage, the frequency of which is probably underestimated because of the difficulty in its diagnosis. We studied the contribution of cardiac magnetic resonance imaging (MRI) in three patients., Observations: Three patients were treated for disseminated tuberculosis. They had moderate cardiac abnormalities (tachycardia, dyspnoea on effort). The electrocardiogram was normal in 2 patients and the echocardiography showed localized hyperkinesias. Cardiac MRI revealed intra-myocardial nodular gadolinium enhancement and hyperkinesias. The clinical outcome in the 3 patients was favourable following anti-tuberculosis therapy; one patient was also administered corticosteroids., Discussion: Cardiac MRI is a non-invasive examination that brought important arguments for the diagnosis of tubercular myocarditis in the 3 patients.

Immune reconstitution inflammatory syndrome (IRIS) occurred in 16 of 37 antiretroviral-naive patients who were treated subsequently for tuberculosis and human immunodeficiency virus (HIV) type 1 infection. IRIS was related to increases in the CD4 cell percentage and in the ratio of CD4 cells to CD8 cells after 1 month of antiretroviral therapy and to dissemination of tuberculosis. These results have implications for the diagnosis of IRIS and the understanding of its pathogenesis.

Background: There is evidence to suggest a pharmacokinetic-pharmacodynamic relationship in HIV-infected patients receiving protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART); however, the effective trough PI plasma concentrations achieved have not been precisely determined., Methods: The relationship between HIV viral load and concomitant PI trough plasma concentration (C(trough)) was evaluated in 101 patients receiving at least 4 months of thrice daily indinavir (IDV)-containing (n=68) or nelfinavir (NFV)-containing (n=33) HAART. The more discriminating C(trough) efficacy thresholds were determined statistically for each PI by using the raw C(trough) and the time-corrected C(trough), using the precise delay since the last PI intake and the half-life of each PI., Results: For IDV (P=0.002) and NFV (P=0.019) median C(trough) levels were higher in patients with undetectable viral load [0.23 mg/L (n=30) and 2.3 mg/L (n=16) respectively] than in patients with detectable viral load [0.11 mg/L (n=38) and 0.6 mg/L (n=17) respectively]. C(trough) levels of IDV (r=-0.45; P<0.0001) and NFV (r=-0.43; P=0.011) were correlated with the concomitant viral load. The more discriminating C(trough) efficacy thresholds were estimated statistically as 0.12 mg/L for IDV and 0.5 mg/L for NFV. When C(trough) values were time-corrected, the C(trough) efficacy thresholds, 8 h after the last intake, were 0.15 mg/L for IDV and 0.65 mg/L for NFV., Conclusions: These results support the importance of achieving minimal effective C(trough) to improve the virological efficacy of PI-containing HAART, and specify the target concentrations for IDV and NFV.

Purpose: To describe information bias due to missing data for hepatitis C (HCV) status in the analysis of factors associated with mortality in HIV-infected patients., Method: The prospective APROCO cohort enrolled 1,151 HIV-infected adults at the first initiation of highly active antiretroviral treatment in 1997-1998. Conversely to other characteristics, hepatitis B and C serologic status were recorded retrospectively., Results: In a first dataset, HCV status was missing in 29%. HCV infection was associated with a higher hazard of death (Cox model, hazard ratio [HR]=4.1; 95% confidence interval [95% CI], 1.5-11.3). After more efforts to actively document HCV status, the information remained missing in only 10%. All deceased patients who were secondarily documented were recorded as being HCV negative. In fact, before systematic collection of HCV status, nonstructured additional documentation for all deaths led to spontaneous notification of HCV-positive serology at death and not HCV negative. HCV was no longer associated with the hazard of death (HR=1.2; 95% CI, 0.6-2.7)., Conclusion: These results underline the need to minimize missing data and to investigate the impact of missing data on the results, although the mechanism of bias is difficult to identify. In addition, these results might shed light on the current debate about the association between HCV and progression of HIV infection.

Whereas valacyclovir is widely used and is recommended by some authors in moderately immunocompromised HIV-infected patients, its use has not been validated by clinical studies. We report a case of herpes zoster in an HIV-infected patient for whom neurologic complication was not avoided despite valacyclovir therapy. Clinical outcome was favorable after intravenous acyclovir. This case suggests careful monitoring of valacyclovir in HIV-infected patients is necessary.

Mycobacteria species other than members of Mycobacterium tuberculosis complex are called non tuberculous mycobacteria (NTM) or "atypical" mycobacteria. To date, about 80 mycobacterial species have been described. They are usually opportunistic pathogens with variable degrees of virulence. Tuberculosis is the commonest mycobacterial disease in the world, followed by leprosy and Buruli ulcer. Before the AIDS epidemic, NTM diseases were confined to the lungs (M. kansasii, M. intracellulare and M. avium), the skin (M. marinum) or cervical lymph nodes (M. scrofulaceum). The outbreak of AIDS epidemic has dramatically changed the epidemiology of NTM diseases. Between 25 to 50% of AIDS patients in Europe and USA are infected with NTM. NTM infections are usually disseminated in patients with profound immunodeficiency. The inflammatory response and the prognosis of NTM diseases depend on the immunological status and the NTM species. Diagnosis may be difficult, especially in AIDS patients in whom numerous diseases are often associated. Diagnostic criteria involve clinical, radiological, microbiological and pathological findings. Identification of Mycobacterium species in cultures is the gold standard. Pathological examination has several interests: it may reveal an NTM disease, it provides a more rapid assessment of the infection than cultures, and helps to evaluate the virulence of NTM species identified by cultures.

In this study, we investigated the cytokine profiles of 14 treatment-naive HIV-infected patients on the initiation of highly active antiretroviral therapy (HAART). At baseline, plasma levels of TNF-alpha and its mRNA in peripheral blood mononuclear cells (PBMC) were highest in the most severely immunocompromised patients (<200 CD4+ cells/mm3). After 12 months of HAART, the virus was undetectable in the plasma of all patients (<200 copies/ml), and median CD4 T cell counts had increased (+164 cells/mm3). We also observed a gradual decrease in the number of proviral DNA copies in PBMC and in immune activation, with lower levels of IFN-gamma mRNA in PBMC associated with weaker activation of CD8+ T cells and lower levels of plasma TNF-alpha. IL-2 mRNA levels in PBMC were found to increase in parallel. The decrease in TNF-alpha and IFN-gamma levels and the increase in IL-2 production appear to be correlated with the efficacy of HAART in naive immunocompromised HIV-infected individuals.

Background: Suboptimal levels of antiretroviral drugs result in virologic failure in HIV-infected patients treated with highly active antiretroviral therapy (HAART)., Objective: To assess the relationship between levels of indinavir in hair and virologic outcome., Design: Cross-sectional study., Setting: 7 AIDS clinics in France., Patients: 89 HIV-infected patients who received HAART that included indinavir., Measurements: Patients were classified as responders or nonresponders on the basis of viremia at the time of hair collection. In nonresponders, levels of indinavir in hair and resistance mutations in the protease gene were assessed at baseline and at the time of indinavir measurement., Results: Mean indinavir levels (+/-SD) were significantly higher in the 65 responders than in the 24 nonresponders (24.4 +/- 16 microg/g vs. 12.9 +/- 8.6 microg/g) (P < 0.001). Nonresponders with intermediate levels of indinavir in hair had more mutations in the protease gene than did nonresponders with low levels of indinavir in hair., Conclusion: Indinavir levels in hair are associated with virologic outcome in patients receiving HAART.

This study attempted to identify factors associated with mortality among human immunodeficiency virus (HIV)-infected adults starting a protease inhibitor (PI)-containing therapy. Among 1155 patients consecutively enrolled in the APROCO study between May 1997 and June 1998, clinical characteristics were as follows: median age, 36 years; median baseline CD4 cell count, 288 cells/mm(3); and median baseline plasma HIV RNA load, 4.4 log(10) copies/mL. After a median follow-up of 27 months, 48 deaths had occurred, of which 44% were related to acquired immune deficiency syndrome. The mortality rate was 2.9% at 12 months. When both data at baseline and data at 4 months after the start of PI therapy were considered, factors independently associated with mortality were (Cox model) low baseline plasma creatinine level, low school education level, low CD4 cell count at 4 months, low hemoglobin level, and elevated hepatic transaminase levels. Thus, social context plus clinical and biologic data, including the 4-month response to treatment, must be considered in treatment of HIV-infected patients.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Mycotic pulmonary aneurysm is an infrequently diagnosed complication of endocarditis. We report here a case of mycotic pulmonary aneurysm and a review of 25 cases from the literature. The mortality rate is greater than 50%. Prompt diagnosis is necessary because early intrasaccular embolization and/or surgical repair is essential to avoid death from rupture of the aneurysm.

We screened 192 patients infected with human immunodeficiency virus (HIV) to examine the relation between CD4+ lymphocyte counts and cytomegalovirus (CMV) viremia and the occurrence of CMV disease and subsequent duration of survival. When we stratified the viremic patients by CD4+ lymphocyte counts, the proportions were as follows: <50/mm3, 20 (25%) of 80 patients; 50-100/mm3, 2 (5.5%) of 36; 101-150/mm3, none of 14; and >150/mm3, 1 (1.5%) of 62. After a mean follow-up period of 8.5 months, 21 (11%) of 192 patients developed CMV disease. The probability of developing CMV disease at 6 months was 13% when the CD4+ lymphocyte count was <50/mm3, 3% when the CD4+ lymphocyte count was 50-100/mm3, and 0 when the CD4+ lymphocyte count was >100/mm3; this probability was 46% for viremic patients and 1% for nonviremic patients. In a multivariate analysis, CMV viremia was independently prognostic of CMV disease (relative risk, 22.03; 95% confidence interval, 6.49-78.97; P < .001), whereas a CD4+ lymphocyte count of <50/mm3 was not (P = .26). These results support the value of CMV viremia for predicting which HIV-infected patients are at risk of developing CMV disease and should therefore receive primary prophylaxis.

The objective of this study was to assess whether patients with CD4+ cell counts <200 x 10(6)/L have a decreased survival after the occurrence of any AIDS-defining event; 187 patients from the placebo arm of a clinical trial of toxoplasmosis prophylaxis (ANRS005-ACTG154) were included. For this analysis, patients were HIV infected without any AIDS-defining event, had a CD4+ lymphocyte count < 200 x 10(6)/L, had a positive serology for Toxoplasma gondii, and had no severe liver, renal, or hematologic abnormalities. We used proportional hazards regression to study the relationships between baseline variables. AIDS-defining events as time-dependent variables, and survival. The risk of dying was increased by 1.9 for a 10-year increase in age and by 1.3 when CD4+ decreased by 50 x 10(6)/L; after the occurrence of a pneumocystosis, a cytomegalovirus infection, or a toxoplasmosis, the risk of dying was multiplied, respectively, by 10.9 (3.0-40.2), 10.0 (2.8-35.4), and 10.0 (4.5-22.2). None of the other AIDS-defining events was associated with an increased risk of dying, but the power to detect such an association was limited. We conclude that the occurrence of pneumocystosis, cytomegalovirus infection, or toxoplasmosis; age; and CD4+ cell count are important determinants of survival for HIV1-infected patients with CD4+ counts < 200 x 10(6)/L who are toxoplasmosis antibody positive.

In randomized placebo-controlled trials in Haïti, Zambia and Uganda, prophylactic use of isoniazid (INH) for 6 to 12 months reduced the annual incidence of tuberculosis in HIV-infected patients by more than 50 per cent. For several years, WHO, IUTATLD and CDC have recommended that HIV-positive patients testing positive in a PPD test should be treated with INH as a form of anti-tuberculosis chemoprophylaxis (ATC). Whilst these recommendations are easy to follow in industrialized countries, widespread use of ATC in developing countries remains problematic because: (i) It is unknown what proportion of patients are likely to be re-infected at the end of ATC in countries where TB is endemic; (ii) It is possible that resistant bacilli may be selected due to the incomplete exclusion from the ATC program of patients with active TB at enrollment; (iii) It is difficult to identify asymptomatic carriers of M. tuberculosis at enrollment; (iv) It is doubtful that all patients will comply with a treatment regime which lasts several months; (v) The cost of a widespread ATC program, whose full benefit remains to be evaluated, may be difficult to justify. This paper attempts to review these issues and demonstrates the need for more population-based clinical trials in the field.

Although drug-induced rash is frequent in human immunodeficiency virus (HIV)-infected patients, rash due to pyrimethamine has not been described previously. In a randomized, double-blind, placebo-controlled study of pyrimethamine as primary prophylaxis for toxoplasmic encephalitis, the incidence of rash (per hundred patient-years) was 8.1 in the pyrimethamine group versus 1.5 in the placebo group (P < .0002). The 1-year incidence of toxoplasmic encephalitis after occurrence of rash was 37%, as compared with 9.6% in the pyrimethamine group without rash, with a 3.7 times higher risk for patients with pyrimethamine-induced rash (P = .001); the incidence was 13% in the placebo group. At the time of toxoplasmic encephalitis, pyrimethamine was successfully readministered to 80% of patients who discontinued it because of rash. Thus, pyrimethamine, when used for prophylaxis, does induce rash in HIV-infected patients. These patients are at higher risk for toxoplasmic encephalitis and should be carefully monitored for it.