Jean Louis Vilde

Treatment of central nervous system toxoplasmosis with pyrimethamine/sulfadiazine combination in 35 patients with the acquired immunodeficiency syndrome. Efficacy of long-term continuous therapy.

Thirty-five patients with the acquired immunodeficiency syndrome (AIDS) and central nervous system toxoplasmosis, seen over a 30-month period, were treated with the combination pyrimethamine/sulfadiazine. All patients had clinical and computed tomographic scan findings consistent with active neurotoxoplasmosis. Mean duration of total therapy was six months. During the first two months of therapy, four patients died of acute neurotoxoplasmosis and 31 showed improvement. Of the 24 patients evaluable for long-term therapy, 14 (58 percent) achieved complete resolution and 10 had late clinical (n = 7) and/or computed tomographic scan (n = 6) sequelae. Six patients experienced 10 relapses, which occurred within six weeks of treatment discontinuation in seven of 10. Reintroduction of the combination led to complete resolution of the relapse in eight cases. These clinical results were correlated with brain anatomic findings in the 15 autopsied cases. Side effects, noted in 25 of 35, were mainly hematologic toxicity (n = 21) and cutaneous rash (n = 12). However, the combination had to be definitively stopped in only two cases and sulfadiazine alone had to be withdrawn in eight other cases. These data suggest that pyrimethamine/sulfadiazine is highly efficacious in neurotoxoplasmosis and that life-long therapy is needed to prevent relapses in patients with AIDS.

Bacterial Prostatitis in Patients Infected with the Human Immunodeficiency Virus

Bacterial prostatitis was diagnosed in 17 of 209 human immunodeficiency virus-infected men hospitalized from October 1985 to October 1987. A history of urogenital disease was found in 13 of 17 patients. Clinical signs of prostatitis were present in 16 of 17 patients, including fever in 13, urinary symptoms in 11 and tender prostate on rectal palpation in 7. Bacteriuria was found in 14 of the 17 patients. Prostatic ultrasound examination showed an abscess in 11 of 16 patients studied. Prostatitis was diagnosed at autopsy in 1 patient. Within 6 weeks after onset of antimicrobial therapy 9 of 13 patients were cured and 4 of 13 did not respond to therapy. Among the 7 patients followed for more than 2 months after the end of antimicrobial therapy 5 had relapse. The prevalence of bacterial prostatitis among human immunodeficiency virus-infected patients increased from 3 per cent in asymptomatic human immunodeficiency virus-infected patients to 14 per cent in patients with the acquired immunodeficiency syndrome.

Relationship between Levels of Indinavir in Hair and Virologic Response to Highly Active Antiretroviral Therapy

Context Current methods for monitoring adherence to and the pharmacokinetics of highly active antiretroviral therapy (HAART) are inefficient and inaccurate. Patient reports tend to overestimate adherence, and blood levels reflect only the medication doses given most recently. A preliminary study suggested that indinavir levels in hair samples were higher in HIV-infected patients who responded to HAART than they were in nonresponders. Contribution This study confirms that indinavir levels in hair are higher in responders to HAART than in nonresponders. Intermediate levels of indinavir in hair were associated with drug-resistant variants of the virus. Implications Measurement of hair levels of antiretroviral drugs deserves further evaluation to establish its role in monitoring HIV-infected patients receiving HAART. The Editors Highly active antiretroviral therapy (HAART) reduces morbidity and mortality from HIV-1 infection (1, 2). Long-term efficacy of HAART depends on strict adherence to prescribed regimens. Suboptimal drug levels are associated with emergence of drug-resistant HIV-1 variants and therapeutic failure (3-6). Because most antiretroviral drugs have a short half-life, monitoring serum and urine levels of protease inhibitors and non-nucleoside reverse transcriptase inhibitors reflects only the last doses ingested (7, 8). The pharmacokinetics of long-term HAART remain unclear because of the failure to adequately monitor antiretroviral treatment. In a small study, we previously showed that indinavir concentrations in hair samples are significantly higher in responders to HAART than in nonresponders (9). Hair growth varies from 0.5 to 1.5 cm each month in individual patients, and a monthly history of circulating drugs can be ascertained from the distribution of drug concentration in hair, which is done with a test called a capillogram (10-13). In the current study, we assessed the association among levels of indinavir in hair, virologic response, and the emergence of drug-resistant variants. Methods Patient Sample One hundred four consecutive drug-naive outpatients gave informed consent and were enrolled in seven clinics that treated AIDS. Before patients began receiving HAART, baseline plasma HIV RNA levels and CD4 cell counts were determined, and plasma samples were separated into aliquots and stored at 80 C. The HAART regimen was indinavir, 800 mg three times daily, and two non-nucleoside reverse transcriptase inhibitors. Indinavir levels were tested only after a patient had received HAART for a minimum of 3 months. Testing Indinavir Concentrations in Hair A small piece of hair (approximately 4 mm in diameter) was cut near the scalp on the neck, leaving an almost undetectable line. If sufficiently long, hair samples were cut into 2-cm segments, frozen at 20 C, and crushed into a powder by an electromagnetic bar (Spex, BioBlock, Paris, France). Indinavir concentrations were determined by using modified high-performance liquid chromatography with a column-switching procedure (8). Eight hair segments from healthy volunteers who were not taking any medications served as controls. The indinavir calibration curves were linear in the range of 2.5 to 100 g/g (R 2 > 0.99). Limit of quantification was 0.5 g/g. Virologic Response and Indinavir Drug Resistance Analysis On the day of hair sampling, patients with a plasma HIV RNA level below the threshold of the assay (500 copies/mL) (Quantiplex HIV-1 RNA 3.0 assay, Chiron Diagnostics Corp., Emeryville, California) were classified as responders. The protease gene was sequenced in paired plasma samples from nonresponders at baseline and on the day of hair sampling. Plasma viral RNA was extracted, and relevant mutations were determined by direct sequencing on reverse transcriptase polymerase chain reaction products (ABI310, Applied Biosystems, Foster City, California). The mutations involved alteration of protease amino acid residues M-46 (to I or L), V-82 (to A, F, S, or T), L-90 (to M), or I-84 (to V), alone or in combination with two minor mutations at residues L-10 (to I), K-20 (to R), M-36 (to I), I-54 (to V or L), A-71 (to V or T), or G-73 (to s) (14-16). Three groups of patients were identified: responders, nonresponders with drug-resistant variants, and nonresponders with indinavir wild-type virus. Statistical Analysis Basic descriptions of the clinical and biological variables are expressed as the mean (SD). These variables were compared by using the Student t-test and, when the sample size was small, by using the MannWhitney U test. The main analysis compared indinavir concentrations in responders and nonresponders by using the Student t-test. In the secondary analyses, we compared indinavir concentrations in nonresponders with mutations and nonresponders without mutations by using the Student t-test. Then, we determined the indinavir concentration that best distinguished these groups of nonresponders from one another by using empirical receiver-operating characteristic curves. The threshold was defined graphically as the best combination of sensitivity and specificity. Finally, indinavir concentration along hair was modeled by using a multivariate regression model that accounted for all available indinavir concentrations. This model included the following fixed effects: Patient group, hair segment number, indinavir treatment duration, and first-order interaction terms. Model and interaction terms were created by assuming a linear relationship, except for patient group. The model took into account clustering by patient. P values of the fixed effects were computed by using the asymptotically consistent estimator method (17). Calculations were performed by using SAS software, version 6.12 (SAS Institute, Inc., Cary, North Carolina). Role of the Funding Sources The funding sources had no role in the collection, analysis, or interpretation of data or in the decision to submit the manuscript for publication. Results Baseline Characteristics Of the 104 patients enrolled in the study, 13 were excluded because their hair samples were less than 2 cm in length, and 2 were lost to follow-up. Of the remaining 89 patients (65 men and 24 women) included in the analysis, 65 were classified as responders (73%) and 24 were classified as nonresponders (27%). At baseline, responders and nonresponders were similar in age, ethnicity (all patients were white), CD4 cell counts, HIV RNA copies, months of indinavir therapy at the time of hair analysis, and reverse transcriptase inhibitors used in their HAART regimens. The mean duration of indinavir treatment (SD) was 14.1 7.0 months. Testing Indinavir Levels in Hair The mean length of hair samples was 3.8 cm (range, 0 to 10 cm). After hair segments were cut, 170 2-cm segments were recovered: 89 scalp-proximal segments (range, 0 to 2 cm), 35 second segments (range, 2 to 4 cm), 20 third segments (range, 4 to 6 cm), 16 fourth segments (range, 6 to 8 cm), and 10 fifth segments (range, 8 to 10 cm. As shown in Figure 1, mean indinavir concentrations [SD] in the proximal segments were significantly higher in responders than in nonresponders (24.4 16.0 g/g vs. 12.9 8.6 g/g) (P < 0.001) (Figure 1) and in the second 2-cm segments (24.4 17.1 g/g vs. 10.6 7.2 g/g) (P = 0.016). Mean indinavir concentrations were also higher in responders than in nonresponders in the third 2-cm segments (13.7 8.7 g/g vs. 9 6.2 g/g) and the fourth 2-cm segments (9.7 7.9 g/g vs. 9.0 4.7 g/g). The difference was not significant, however, probably because of the small sample size. Figure 1. Mean indinavir concentration in the first 2-cm segment of hair in patients who responded or did not respond to highly active antiretroviral therapy that included indinavir. Resistance Analysis We evaluated genotype resistance to indinavir in 21 of the 24 nonresponders (87%); 2 samples were inadequate, and 1 sample could not be amplified. At baseline, before HAART was initiated, only 1 nonresponder had a drug-resistant HIV-1 variant (mutations M-46 [I to L] and L-90 [to M]). This patient had the highest indinavir concentration among all nonresponders. Twelve nonresponders harbored indinavir-resistant HIV-1 variants, and nine nonresponders harbored indinavir-susceptible HIV-1 variants. The nonresponders with indinavir-resistant HIV-1 variants had higher mean indinavir levels than did the nonresponders with no mutations (14.5 8.4 g/g vs. 8.5 7.9 g/g [P = 0.075] in the first 2-cm segments, 17.9 4.8 g/g vs. 7.0 4.1 g/g [P = 0.03] in the second 2-cm segments, and 14.4 0.1 g/g vs. 6.3 5.9 g/g [P = 0.15] in the third 2-cm segments). Figure 2 shows an empirical receiver-operating characteristic curve, using indinavir concentration in the first hair segment. A threshold of 11.4 g/g distinguished patients with resistant HIV-1 variants from those who did not have resistant HIV variants; the threshold corresponds to a sensitivity of 0.75, a specificity of 0.78, a positive predictive value of 0.82, and a negative predictive value of 0.70. Multivariate regression analysis, which included all available hair segment concentrations in a single model, revealed that the overall mean concentrations of indinavir in hair (SD) differed significantly among responders (22.1 2.6 g/g), nonresponders with mutations (14.0 3.7 g/g), and nonresponders without mutations (8.5 3.9 g/g) (P < 0.001). In addition, the overall mean concentration of indinavir was significantly lower in samples that were farther from the scalp (decrease, 5.0 0.9 g/g from one hair segment to the next) (P < 0.001). The magnitude of this decrease along the length of the hair was significantly reduced by 0.2 0.1 g/g for every month that indinavir treatment continued (P = 0.01). In nonresponders with mutations, the magnitude of this decrease along the length of the hair was further reduced by 2.7 1.0 g/g compared with patients in the other groups (P < 0.001). No other statistically significant effect or interaction was found to be associat

Ruptured mycotic pulmonary artery aneurysm: an unusual complication of right-sided endocarditis.

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.

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.

Patients schizophrènes infectés par le VIH traités par antirétroviraux

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.Resume Objectif La schizophrenie pourrait apparaitre comme un obstacle a la mise en route et a l’observance d’un traitement antiretroviral chez des patients infectes par le VIH. L’objectif de ce travail est de decrire l’evolution clinique et biologique de 7 patients schizo-phrenes (diagnostic pose selon les criteres du DSM-IV-R) infectes par le VIH, chez lesquels une multitherapie antiretrovirale a ete instauree. Observations Une prise en charge multidisciplinaire associant infectiologue, psychiatre, assistante sociale, alcoologue, structures d’observance, de soins aux usagers de drogues et de soins a domicile, et associations a ete realisee, avec suivi medico-psychiatrique au moins mensuel et coordonne. Il s’agissait de 6 hommes et 1 femme, âges de 26 a 48 ans. Pour 5 patients, la schizophrenie etait connue depuis 6 mois a 20 ans avant le diagnostic d’infection par le VIH. Pour les 2 autres patients, le diagnostic semblait proche de la decouverte de l’infection. Tous recevaient un traitement neuroleptique au long cours. Deux d’entre eux etaient toxicomanes actifs, puis substitues. Avant le debut du traitement antiretroviral, 6 patients avaient une infection avancee, stade C, nadir des CD4 de 6 a 70/mm 3 , tandis qu’un patient avait une primo-infection VIH. Un traitement avec inhibiteurs de protease (IP) avait ete debute chez 6 patients entre mai 1996 et aout 1997, et en juillet 1998 pour le dernier, pris en charge a cette date. La reponse au traitement antiretroviral par IP a ete lente chez tous les patients, la charge virale (CV) devenant indetectable apres 5 mois a 4 ans chez 6/7 patients, avec, pour 3 d’entre eux, la survenue d’infections opportunistes. Chez 5 patients, elle est restee indetectable jusqu’en janvier 2002 (arret de l’etude) avec des CD4 entre 45 et 1 000/mm3 ; 1 patient est decede de cirrhose terminale mixte (ethylisme et hepatite C), 1 autre avait une CV partiellement controlee a 10 000 copies/mL, en rapport avec une observance incomplete. Conclusion Les patients schizophrenes infectes par le VIH peuvent avoir une reponse favorable aux traitements antiretroviraux, meme si elle apparait lente, et une bonne observance de ceux-ci, meme complexes, a condition d’une prise en charge soutenue, multidisciplinaire, coordonnee et perseverante.

Upper Respiratory Tract Involvement in the Course of Diffuse Infiltrative Lymphocytosis Syndrome in HIV-1—Infected Patients: Report of 2 Cases

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.

Septicémie et pneumonie dues à Salmonella kiambu après inhalation de guano de pigeon

A case of septicemia and pneumonia due to Salmonella Kiambu after inhalation of pigeon feces is reported. Prevention of airways contamination is needed when cleaning areas highly contaminated with pigeon feces.

Aspects évolutifs de la maladie de Still de l'adulte. À propos de 17 observations

The outcome in 17 patients with adult Stills disease is reported. All patients were in ARA functionnal class I at the end of follow-up. Chronic articular disease was observed in only two cases and methotrexate was an effective therapy.