Safety and efficacy of raltegravir in HIV-infected transplant patients cotreated with immunosuppressive drugs.

Solid organ transplantations (SOT) are performed successfully in selected HIV-infected patients. However, multiple and reciprocal drug-drug interactions are observed between antiretroviral (ARV) drugs and calcineurin inhibitors (CNIs) through CYP450 metabolization. Raltegravir (RAL), a novel HIV-1 integrase inhibitor, is not a substrate of CYP450 enzymes. We retrospectively reviewed the outcomes of 13 HIV-infected transplant patients treated by an RAL + two nucleosidic reverse transcriptase inhibitor (NRTI) regimen, in terms of tolerability, ARV efficacy (plasma viral load, CD4 cell count), drug interactions, RAL pharmacokinetics and transplant outcome. Thirteen patients with liver (n = 8) or kidney (n = 5) transplantation were included. RAL was initiated (400 mg BID) either at time of transplantation (n = 6), or after transplantation (n = 7). Median RAL trough concentration was 507 ng/mL (176-890), which is above the in vitro IC95 for wild type HIV-1 strains (15 ng/mL). Target trough levels of CNIs were promptly obtained with standard dosages of tacrolimus or cyclosporine. RAL tolerability was excellent. There was no episode of acute rejection. HIV infection remained controlled. After a median follow-up of 9 months (range: 6-14), all patients were alive with satisfactory graft function. The use of an RAL + two NRTI-based regimen is a good alternative in HIV-infected patients undergoing SOT.

Risk factors for anaemia in human immunodeficiency virus/hepatitis C virus-coinfected patients treated with interferon plus ribavirin.

The most frequent and the most troublesome adverse effect of interferon plus ribavirin-based therapy is anaemia. The aim of this analysis was to determine the incidence and risk factors of anaemia (Hb < 10 g/dL) in human immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy. We reviewed all cases of anaemia occurring among 416 patients participating in a randomized, controlled 48-week trial comparing peginterferon (peg-IFN) alpha 2b plus ribavirin with interferon alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, HCV therapy and clinical and laboratory findings. Sixty-one (15.9%) of the 383 patients who received at least one dose of anti-HCV treatment developed anaemia. In multivariate analysis the risk of anaemia was significantly associated with zidovudine (OR, 3.27 95% CI, 1.64-6.54, P = 0.0008) and peg-IFN (OR, 2.35; 95% CI, 1.16-4.57, P = 0.0179). The risk of anaemia was lower in patients with higher baseline haemoglobin levels (OR, 0.35 95% CI, 0.26-0.49, P < 0.0001) and in patients receiving protease inhibitor-based antiretroviral therapy (OR, 0.51 95% CI, 0.30-0.86, P = 0.0114). Zidovudine discontinuation could help to avoid anaemia associated with anti-HCV therapy.

[Study of the usefulness of pharmacist consultations for patients on antiretroviral regimens]. / Enquête sur la mise en place d'une consultation pharmaceutique pour les patients sous antirétroviraux.

OBJECTIVE: Highly active anti-retroviral therapies (HAART) in HIV treatment can result in complex treatment regimens. We surveyed HIV patients followed in the infectious disease department of Saint-Germain-en-Laye Hospital to assess the interest of offering patients a consultation with a pharmacist. METHODS: The 3-part questionnaire enabled us to assess the medical and pharmaceutical information given to the patient, adherence, and risk factors for poor observance. The questionnaire was distributed to all patients, regardless of whether they were receiving treatment. A simple adherence score was computed as well as a score for the risk of poor adherence. RESULTS: Ninety patients returned analyzable questionnaires: 65 (72.2%) thought a pharmaceutical consultation would be useful. They felt it should cover in priority the following subjects: drug interactions (51%), secondary effects (49%), and what to do after forgetting a dose (44%). Treatment was perceived as positive by 82 patients (91%) and tolerated well by 57 (65%). Sixty patients (66.3%) reported that they occasionally forgot a dose, 37 (41.3%) that they regularly did. The results showed good adherence by 61.3% and poor adherence by 38.5%. Risk of non-adherence was significantly associated with three factors: the number of pills to take, the number of daily doses, and the length of the treatment. CONCLUSION: Our survey shows the interest of consultations with pharmacists as a clinical service. By reinforcing the patient's understanding, these can complete and supplement the physician's explanation and instructions on pharmaceutical topics, especially those that could not be addressed during the clinical visit. The main aim of this process is to improve adherence, which is a key element in treatment efficacy.

[Primary Neisseria meningitidis arthritis of the knee without meningitis: contribution of synovial fluid culture in blood-culture vial]. / Monoarthrite du genou à Neisseria meningitidis sans méningite: apport de la culture du liquide articulaire en flacon d'hémoculture.

INTRODUCTION: Primary meningococcal arthritis is a rare form of meningococcal disease. It occurs as an isolated acute purulent arthritis without meningitis, and presence of Neisseria meningitidis in articular fluid. We report a new case of typical primary meningococcal arthritis. EXEGESIS: A previously healthy 23-year-old female patient was admitted for purpuric lesions of the legs. At admission, conscience was normal and symptoms of meningitis were absent. During the 2nd day of hospitalisation, a warm and painful effusion in the right knee appeared. Aspiration from the right knee yielded a purulent fluid. N. meningitidis was isolated from a blood-culture vial inoculated with the synovial fluid, while blood cultures remained sterile. Anti-biotherapy was initiated as soon as microbiological diagnosis was established. The patient was symptom-free 1 month later. CONCLUSION: We emphasize the fact that agar cultures of the synovial fluid remained sterile, while N. meningitidis grew in a blood-culture vial. We suggest that diagnosis of primary meningococcal arthritis may be underestimated when inappropriate culture media are used.

[Activated C protein resistance manifested by cutaneous necrosis after interferon alpha injection: case report]. / Nécrose cutanée après injection d'interféron alpha révélant une résistance à la protéine C activée: rapport d'un cas.

INTRODUCTION: Cutaneous necrosis occurring in the course of treatment by alpha interferon is an uncommon side-effect. Its physiopathologic mechanism remains obscure. A local thrombotic action of interferon has been suggested to explain its occurrence. EXEGESIS: A 64-year-old male patient with human immunodeficiency virus-related cutaneous Kaposi's sarcoma presented cutaneous necrosis after a 9-month treatment by interferon alpha, while his resistance to activated protein C had already been demonstrated. To our knowledge, this is the first case ever described regarding the association of interferon-induced cutaneous necrosis with activated protein C resistance. CONCLUSION: This suggests that in case of interferon treatment-induced cutaneous necrosis coagulation disorders should be investigated and questions the existence of a particular "pro-coagulant profile" facilitating this side effect.

Prevalence of and risk factors for Clostridium difficile colonization at admission to an infectious diseases ward.

A study of 240 consecutive admissions to a single hospital ward over a 6-month period was conducted to determine the prevalence of and risk factors for Clostridium difficile colonization at admission. The prevalence rate of C. difficile colonization at admission was 13.3%. Seventy-four percent of the patients admitted to the ward were infected with human immunodeficiency virus (HIV). Multivariate analysis identified three risk factors for C. difficile colonization: clindamycin use (adjusted odds ratio [OR], 9.4; P < .001), penicillin use (adjusted OR, 3.9; P = .018), and a history of cytomegalovirus infection (adjusted OR, 4.2; P = .02). C. difficile colonization at admission to our infectious diseases ward was common. Antibiotic treatments received before admission were the main risk factors for C. difficile colonization. HIV infection per se was not associated with C. difficile colonization. It is interesting that there was an association between C. difficile colonization and a history of cytomegalovirus infection.

AIDS-associated cytomegalovirus infection mimicking central nervous system tumors: a diagnostic challenge.

We reviewed cases of cytomegalovirus (CMV) infection of the central nervous system (CNS) that initially masqueraded as tumors in 37 of 543 consecutive patients infected with human immunodeficiency virus (HIV) and CMV who were seen at the Pasteur Institute Hospital and Saint-Louis Hospital (Paris) between 1992 and 1994. We detail the clinical features of three patients who presented with ring-enhanced space-occupying lesions mimicking CNS tumors. They were all profoundly immunodepressed (mean CD4 cell count, 13/mm3). Magnetic resonance imaging (MRI) showed enlargement of the spinal cord in one case, consistent with a space-occupying lesion and showing gadolinium enhancement; in the other two cases, ring-enhanced mass lesions were seen in the cerebral hemispheres. In all three cases marked edema and a mass effect were present. Image-guided stereotactic biopsies confirmed the diagnosis of CMV infection. The three patients' conditions improved with specific therapy. MRI showed enhanced focal intraparenchymal lesions consistent with marked focal necrosis, probably related to the severity of immunodepression, as HIV infection had been diagnosed several years previously. CMV infection should be considered as a cause of ring-enhanced space-occupying mass lesions in patients with HIV-1 infection. Earlier identification of these unusual tumorlike forms of CMV infection by means of MRI should result in improved outcome.

Multicentric Castleman's disease in HIV infection: a clinical and pathological study of 20 patients.

OBJECTIVES: To describe, in a retrospective study, the clinical and pathological spectrum of multicentric Castleman's disease (MCD) in HIV infection. PATIENTS: The diagnosis of MCD was established by lymph node biopsy in 20 HIV-infected patients. All patients had been HIV-infected by sexual contact. At diagnosis, HIV infection was asymptomatic in eight patients and Kaposi's sarcoma was present in 12. Mean +/- SD CD4+ cell count was 156 +/- 99 x 10(6)/l. RESULTS: Patients were referred with a syndrome of fever and splenomegaly (100%), peripheral lymphadenopathy (90%), hepatomegaly (70%), severe weight loss (70%), respiratory symptoms (65%) and oedema (55%). Anaemia was a constant finding and seven (35%) patients presented with pancytopenia. Serum markers of inflammation were present in most patients: a high level of C reactive protein (90%), polyclonal hypergammaglobulinaemia (89%) and hypoalbuminaemia (56%). The histological pattern of the lymph nodes was characterized by small hyalinized germinal centres surrounded by concentric layers of small lymphocytes, vascular hyperplasia, hyalinized vessels and large interfollicular sheets of plasma cells. Five patients were classified as plasma cell type MCD and 15 as hyaline vascular/plasma cell (mixed) type. Immunophenotyping studies (n = 13) demonstrated a polyclonal B-cell process. No linkage with Epstein-Barr virus (EBV) could be demonstrated immunohistochemically using an anti-latent membrane protein-1 monoclonal antibody (n = 16) or by RNA in situ hybridization with an EBV-encoded RNA transcript-specific probe (n = 13). Remission was obtained with low-dose and usually single agent chemotherapy in 16 patients. During follow-up, non-Hodgkin's lymphoma developed in two patients and Kaposi's sarcoma in three. Fatal outcome occurred in 14 patients with a median survival of 14 months. CONCLUSION: MCD associated with HIV infection is a distinct clinico-pathological entity that can be differentiated from other types of HIV-associated systemic lymphoproliferative disorders. It is very similar to MCD observed in non-HIV-infected patients, except for the high prevalence of pulmonary symptoms and for the stronger association with Kaposi's sarcoma. Single-agent chemotherapy with vinblastine is effective and may prolong survival.

Campylobacter infections in HIV-infected patients: clinical and bacteriological features.

OBJECTIVE: To study the clinical and bacteriological features of Campylobacter infections in HIV-infected patients. DESIGN: A retrospective analysis (1989-1992), followed by a prospective analysis (1992-1994). SETTING: Hospital HIV inpatient unit. PATIENTS AND METHODS: All patients with Campylobacter spp. identified by the laboratory of microbiology at Saint-Louis Hospital, Paris were studied, and their clinical features as well as their response to therapy recorded. RESULTS: During the study period, Campylobacter infection was documented in 38 HIV-infected patients, 76% of whom had AIDS. Campylobacter spp. was isolated from stools in 36 cases and from blood cultures in four cases. Species identification yielded C. jejuni (84%) and C. coli (16%). High-level resistance to quinolones was frequently observed (21%), but resistance to erythromycin (3%) and tetracycline (5%) was rare. Diarrhoea, fever and abdominal pain were the main clinical features of infection. Other intestinal pathogens were found in 42% of patients. Most patients had an acute illness with rapid resolution under appropriate antimicrobial therapy. However, eight patients (21%), experienced chronic diarrhoea with persistent isolation of Campylobacter and in vivo selection of resistant strains, requiring multiple courses of antibiotics. CONCLUSIONS: Campylobacter usually cause acute diarrhoea in patients with HIV infection. Antimicrobial therapy should be guided on in vitro susceptibility testing because of the prevalence of antibiotic resistance. Despite appropriate therapy, some patients will present with prolonged diarrhoea and in vivo selection of multiresistant isolates.

[Pseudo-tumoral cystitis due to Toxoplasma in an patient with AIDS]. / Cystite pseudo-tumorale à toxoplasme chez un patient atteint de SIDA.

The authors report a case of cystitis due to Toxoplasma Gondii infection in a patient suffering from AIDS. Initial symptoms consisted of dysuria, extreme frequency and urgent micturition responsible for pseudo urinary incontinence. Urine culture was sterile. Pelvic computed tomography and pelvic MRI demonstrated thickening of the bladder wall and seminal vesicles. Cystoscopy confirmed the presence of an intravesical proliferation with a pseudoneoplastic appearance. The diagnosis of Toxoplasma cystitis was confirmed by the discovery of Toxoplasma cysts on histological examination of bladder biopsies. Toxoplasma cystitis is a rare cause of pseudoneoplastic bullous cystitis in HIV-seropositive patients.

Toxoplasma-induced cystitis in a patient with AIDS.

We report a case of cystitis due to Toxoplasma gondii in a patient with AIDS who presented with dysuria and urinary frequency. To our knowledge, this is the first reported case of cystitis due to this organism. Microscopy of bladder specimens revealed inflammatory cystitis, with Toxoplasma cysts disseminated within the mucosa. No other pathogen could be detected by urine culture, cytoscopy, or staining of bladder specimens obtained at autopsy. Diagnosis of cystitis due to Toxoplasma gondii may be difficult because this illness is associated with misleading radiologic and endoscopic findings. Toxoplasmosis is a rare but potentially curable cause of culture-negative cystitis in patients with AIDS.

Risk factors for Clostridium difficile-associated diarrhoea in HIV-infected patients.

OBJECTIVE: To identify risk factors associated with a first episode of Clostridium difficile-associated diarrhoea (CDAD) in patients with HIV infection. DESIGN: A case-control study. SETTING: University teaching hospital HIV inpatient unit. PATIENTS AND METHODS: Nineteen HIV-infected patients with CDAD, defined as diarrhoea with positive stool culture for Clostridium difficile (CD) and positive stool cytotoxin B assay, were compared with 38 randomly selected controls (HIV-infected patients hospitalized on the ward on the day the matched case was diagnosed). CD isolates were phenotyped by electrophoretic protein patterns. RESULTS: The incidence of CDAD among HIV-infected patients was 4.1/100 of patient-admissions. On univariate analysis, cases were more likely to have used clindamycin [11 out of 19 compared with four out of 38; odds ratio (OR) 19; 95% confidence interval (CI), 2-160; P = 0.0007], and pyrimethamine (14 out of 19 compared with 13 out of 38; OR, 4.8; 95% CI, 1.4-16, P = 0.02) in the month before diagnosis, and to have had cerebral toxoplasmosis (12 out of 19 compared with 13 out of 38; OR, 2.8; 95% CI, 0.9-8.6; P = 0.09). There was also a significant increase of the risk of CDAD as duration of hospitalization in the ward increased (chi 2 for trend, P = 0.007). Multivariate models associated two risk factors with CDAD: clindamycin use (OR, 42; 95% CI, 2-813; P = 0.01), and prolonged hospitalization in the ward (OR, 3.6 per week in the ward; 95% CI, 1-13, P = 0.048). Of 18 available CD isolates, 15 (83%) had identical electrophoretic protein pattern. CONCLUSIONS: Clindamycin use and prolonged hospitalization in the ward were the main risk factors associated with CDAD in this study. These observations, together with the occurrence of one major phenotype of CD, suggest nosocomial transmission of CD in the ward.