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J P Chave

Publications and source records attributed to J P Chave.

At least 19 recordsLinked to original sources

[Fever of unknown origin in a cohort of HIV-positive patients].

The purpose of this study was to determine the prevalence of fever of unknown origin (FUO) in a cohort of HIV positive patients and to describe their evolution and the final diagnosis. The clinical records of 412 patients followed from January 1987 to December 1990 at our HIV outpatient clinic were reviewed: in 151 patients 255 episodes of fever had been observed of which 22 (in 21 patients) met the criteria for FUO. 19 patients (90%) presented with a CDC/WHO stage IV HIV infection and the mean CD4+ lymphocyte count was 0.160 G/l. The etiology was ultimately determined in 13/22 episodes (3 Pneumocystis carinii pneumonia, 3 invasive infections due to atypical mycobacteria, 2 bacterial pneumonia, 1 Cytomegalovirus colitis, 1 Isospora belli enteritis, 1 visceral leishmania, 1 candida septicemia and 1 lymphoma). In 6/22 episodes, the fever subsided after zidovudine was started and was therefore attributed to HIV itself. In 3/22 episodes no etiology was found. In conclusion, this series shows that FUO is usually seen in advanced HIV infection and that it often represents an early sign of opportunistic infection. This observation underlines the importance of follow-up, since it finally served to detect the etiology of FUO in 86% of cases. Trial treatment with zidovudine can be useful where no pathology has been discovered despite 3 weeks' follow-up and appropriate investigations.

AIDS-Related Opportunistic Infections

Toxoplasma encephalitis in patients with the acquired immunodeficiency syndrome.

Among 504 cases of AIDS diagnosed between 1983 and 1990, there were 86 patients (17%) with toxoplasma encephalitis (TE). All were symptomatic at the time of diagnosis. General signs such as fever, neck stiffness, or headache were present in 87.2%, and 75.6% had focal signs. The primary means of diagnosis was computerized tomographic scanning, revealing 169 lesions of which 80% were immediately contrast-enhancing. All patients had IgG antibodies against Toxoplasma gondii either before (74 of 75 evaluable patients) or at the time of diagnosis of TE (73 of 75). Elevated antibody titers were present in 44% of evaluable patients, compared to 11% of patients with AIDS and other opportunistic infections. Initial treatment was pyrimethamine plus sulfonamides in 65 patients, and pyrimethamine plus clindamycin in 12 patients, with other combinations or no treatment accounting for the remainder. Life-table analysis of the time to discontinuation of treatment because of suspected side effects suggested that sulfadiazine was significantly more toxic, with 48% of patients experiencing an interruption in treatment after 30 days, than pyrimethamine (12%) or clindamycin (24%). The 30-day mortality rate was 12%, and median survival was 310 days after diagnosis, 530 in patients treated with zidovudine and 190 days in those not so treated. Of 82 evaluable patients, 16 relapsed once and 4 of these more than once. The risk of relapse was 27% 1 year after diagnosis of a first episode of TE.

Acquired Immunodeficiency Syndrome

Once-a-week azithromycin in AIDS patients: tolerability, kinetics, and effects on zidovudine disposition.

Toxoplasmic encephalitis is one of the leading causes of morbidity in patients with AIDS. Lifelong treatment is needed to prevent relapses, and primary prevention is desirable in high-risk patients, but the available drugs are often poorly tolerated. Azithromycin (AZM) has been considered a drug candidate because of its efficacy in the animal model and its kinetic properties, which would allow intermittent administration. The tolerability and kinetics of AZM and its effect on the disposition of zidovudine (ZVD) were therefore evaluated in a preliminary open study in nine human immunodeficiency virus-infected patients. AZM was administered once weekly for 5 weeks 2 h before the usual morning ZVD dose. The day before and on the first and fifth AZM dosings, blood samples were drawn every 30 min during 5 h for determination of the concentrations of ZVD and its glucuronide metabolite. Blood samples were drawn for AZM measurement over 72 and 360 h on the first and fifth AZM administrations, respectively, as well as before and 3 h after dosing on the second, third, and fourth AZM dosings. After the first and fifth administrations, maximum AZM concentrations in serum were 0.6 +/- 0.1 and 0.8 +/- 0.2 microM (mean +/- standard error of the mean), respectively; times to peak concentration in serum were 3.7 +/- 0.2 and 2.9 +/- 0.4 h, respectively; areas under the plasma concentration-time curves were 9.2 +/- 1.6 and 9.3 +/- 2.0 micrograms.h/ml, respectively; and half-lives were 61.0 +/- 5.4 and 63.8 +/- 6.7 h, respectively. On days -1, 1, and 29, ZVD kinetic parameters were as follows: maximum concentrations in serum, 3.1+/- 0.6, 4.3 +/- 0.6, and 4.2 +/- 0.9 microM, respectively; times to maximum concentrations in serum, 1.1 +/- 0.4, 0.8 +/- 0.2, and 1.2 +/- 0.3 h, respectively: areas under the plasma concentration-time curves, 5.3 +/- 0.9, 5.9 +/- 0.6, and 5.7 +/- 0.8 microgram . h/ml, respectively; and half-lives, 1.3 +/- 0.08, 1.4 +/- 0.04, and 1.3 +/- 0.04 h, respectively. Except for transient mild abdominal cramps that occurred at 2 to 3 h postdose (6 of 45 exposures) and nausea (4 of 45 exposures), neither subjective nor objective side effects were observed. The kinetics of AZM were similar after the first and repeated administrations, and the disposition of ZVD was not altered by this treatment. The efficacy of AZM in preventing cerebral toxoplasmosis can therefore be safely tested in human immunodeficiency virus-infected patients concomitantly treated with zidovudine.

Acquired Immunodeficiency Syndrome

Chronic Mycobacterium avium complex infection of the central nervous system in a nonimmunosuppressed woman.

We report the case of a woman who developed chronic meningitis and a brain abscess due to Mycobacterium avium, without immunosuppressed state. She was treated with antituberculous drugs but the infection progressed and she died 4 years after first becoming ill. The occurrence of CNS infection with M. avium in the absence of acquired immunosuppression is rare. Its diagnosis is difficult, delaying clinical recognition and appropriate therapy.

Adult

Trimethoprim, alone or in combination with sulphamethoxazole, decreases the renal excretion of zidovudine and its glucuronide.

Trimethoprim and trimethoprim-sulphamethoxazole (co-trimoxazole) are often prescribed in HIV patients treated with zidovudine. The pharmacokinetics of zidovudine, after a dose of 3 mg kg-1 by constant rate intravenous infusion over 1 h were evaluated in nine HIV patients in an open, randomized, three-phase crossover study, without and with trimethoprim (150 mg) and trimethoprim-sulphamethoxazole (160 and 800 mg). The metabolic clearance of zidovudine was not significantly influenced by trimethoprim-sulphamethoxazole and trimethoprim. However, the renal clearance of zidovudine was decreased by 58 and 48%, respectively, and that of its glucuronide by 27 and 20% (P < 0.05). The fraction of the dose excreted as the parent compound fell by 47 and 39% and the metabolic ratio by 48 and 43% (P < 0.05). This kinetic drug interaction, apparently due solely to trimethoprim, may only be clinically important when hepatic glucuronidation is also impaired by liver disease or inhibited by other drugs.

Adult

[Telephone duty "AIDS Information" at the Vaudois University Hospital Center: who calls and why?].

From January 1989 to December 1990, 7653 phone calls were answered by the AIDS Hot Line of the Centre Hospitalier Universitaire Vaudois. Most of the calls were from the general public (82%), 12% from health care workers and 6% from HIV-infected subjects. The main reasons for calling were information regarding the HIV test (public), scientific inquiries (health care works) and requests for medical or social support (HIV-positive persons). With more than 15 phone calls per day, this hot line fulfils a definite need with respect to the various types of information required.

AIDS Serodiagnosis

Treatment for cerebral toxoplasmosis protects against Pneumocystis carinii pneumonia in patients with AIDS. The Swiss HIV Cohort Study.

OBJECTIVE: To determine whether long-term maintenance treatment for toxoplasmosis protects against Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Cohort study. SETTING: Switzerland. PATIENTS: A total of 453 patients with human immunodeficiency virus (HIV) entered the Swiss HIV Cohort Study. Ninety-nine patients with cerebral toxoplasmosis but no previous or simultaneous P. carinii pneumonia were compared with 240 patients with AIDS and other severe opportunistic infections (Centers for Disease Control [CDC] stage IVC1 infection other than toxoplasmosis and P. carinii pneumonia) as well as with 114 patients receiving inhaled pentamidine in a study of primary pneumocystis prophylaxis in patients infected with HIV. MEASUREMENTS: Life-table analysis for P. carinii-free survival. MAIN RESULTS: Six of 99 (6%) patients with toxoplasmosis, 50 of 240 (21%) patients with other severe opportunistic infections, and 8 of 114 (6%) patients receiving inhaled pentamidine developed P. carinii pneumonia. Life-table analysis showed that the incidence of pneumonia was substantially lower in patients with toxoplasmosis compared with that in patients with other severe opportunistic infections and was similar to the incidence in patients receiving pentamidine as prophylaxis. Analysis of the medication records from patients with toxoplasmosis showed that pyrimethamine and sulfonamides were administered 50% of the time; pyrimethamine and clindamycin, 25% of the time; and pyrimethamine alone, 9.9% of the time but that only one of the six patients with toxoplasmosis who developed P. carinii pneumonia received pyrimethamine and sulfonamides in the month before diagnosis. CONCLUSION: Patients with cerebral toxoplasmosis have a low risk for subsequently developing P. carinii pneumonia. This decreased risk is probably the result of chronic suppressive treatment with pyrimethamine and sulfonamides.

Acquired Immunodeficiency Syndrome

Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi's sarcoma.

A combination of oral zidovudine (250 mg twice daily) and subcutaneous interferon-alpha (10 x 10(6) units daily) was evaluated for clinical, antiretroviral, and immunological efficacy and for side effects in 17 patients with AIDS-related Kaposi's sarcoma. Fifteen patients were evaluable. During the study period of 12 weeks, tumor responses were complete in two patients and partial in two patients (27% major response rate). Minimal responses were seen in two patients (40% overall response rate). An anti-HIV effect (reduction of serum p24 antigen by 70% or more) was observed in seven of ten evaluable patients who were initially antigenemic. CD4 lymphocyte counts remained unchanged. In six patients who had either a tumor response or a marked decline of HIV antigenemia, the treatment was continued between 12 and 59 weeks beyond the study period. Two of four patients with tumor regression at 12 weeks had an additional tumor response in this period despite prior dose reduction of interferon due to toxicity. Late progression of KS was eventually observed in four of six patients on prolonged treatment. The responsiveness of Kaposi's sarcoma seen in this study in patients with low CD4 counts and prior constitutional symptoms (fever, weight loss) was unexpected and needs further confirmation by larger patient groups. Dose-limiting toxicities were bone marrow depression (severe anemia in four and neutropenia with anemia in two patients), subjective adverse experiences (fever, fatigue, myalgia; four patients) and both (two patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

A controlled study of inhaled pentamidine for primary prevention of Pneumocystis carinii pneumonia.

BACKGROUND: Current recommendations for prophylaxis of Pneumocystis carinii pneumonia (PCP) are based on data from patients who have had at least one episode of PCP (secondary prevention). We designed a study to determine the efficacy and side effects of inhaled pentamidine in the primary prevention of PCP. METHODS: Two hundred twenty-three patients sero-positive for human immunodeficiency virus (HIV) who had the acquired immunodeficiency syndrome (AIDS) but not PCP, who had advanced AIDS-related complex, or who had less than 0.2 x 10(9) CD4-positive lymphocytes per liter received either 300 mg of pentamidine isethionate or 300 mg of sodium isethionate every 28 days by inhaler. The proportion of patients surviving without PCP was analyzed with the log-rank test as a function of time spent in the trial, according to the intention to treat with either placebo or pentamidine. RESULTS: The third of five planned interim analyses showed a significant difference in the occurrence of PCP, with 8 cases in pentamidine group and 23 in the placebo group (nominal P value = 0.0021). There were no deaths within 60 days of the diagnosis of PCP and no significant differences in survival between groups. Approximately 53 inhalations were needed to prevent one episode of pneumonia. Thirty-eight of 114 patients given pentamidine (33 percent) and 7 of 109 given placebo (6 percent) had moderate-to-severe coughing during inhalations (two-tailed P less than 0.00001), which caused 4 patients given pentamidine (3.5 percent) to discontinue taking it. CONCLUSIONS: A dose of 300 mg of aerosolized pentamidine given every four weeks was well tolerated and 60 to 70 percent effective in preventing a first episode of PCP in patients with HIV infection.

AIDS-Related Complex

Sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman disease) in an HIV-positive patient.

We report a case of a 31-year-old HIV infected black female, who presented with asymptomatic generalized lymphadenopathy. Three particularly enlarged lymph nodes were biopsied (2 cervical and 1 axillary). The histological picture was consistent with a diagnosis of sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease. Large histiocytes, positive for a variety of macrophage markers and for the S-100 protein, were observed in the distended sinuses. A few hyperplastic follicles, such as usually seen in HIV-infection-associated lymphadenopathy, were present at the periphery of one lymph node. No infections agent besides HIV could be detected by histological or microbiological analysis or by in situ hybridization. This is the first reported case of SHML associated with HIV infection. The possible relationship between the two diseases is discussed.

Adult

Transmission of Pneumocystis carinii from AIDS patients to other immunosuppressed patients: a cluster of Pneumocystis carinii pneumonia in renal transplant recipients.

Five renal transplant recipients developed Pneumocystis carinii pneumonia (PCP) over a 22-month period, while no cases had been observed over a 5-year period in 114 transplanted patients treated with the same immunosuppressive protocol. All patients were HIV-negative, and no modification in diagnostic techniques for P. carinii could account for this observation. All five patients developed PCP within 2 months of an acute graft rejection episode. All of them attended the same outpatient facility as AIDS patients attending the hospital, where they shared the waiting and treatment rooms. Comparison of cases with matched controls was possible in three instances and revealed that the cases had had more outpatient clinic encounters with AIDS patients who had presented, or subsequently developed, PCP. This observation suggests that AIDS patients developing PCP may transmit the infection to other immunosuppressed patients.

Acquired Immunodeficiency Syndrome

[AIDS today].

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Acquired Immunodeficiency Syndrome

Multiple site avascular necrosis in HIV infected patients.

We describe avascular necrosis at multiple sites in 2 young adults. This is a condition rarely seen except in hypercortisonism or hemoglobinopathies. In one case, it occurred in the first trimester of pregnancy. No obvious cause of osteonecrosis could be found but both patients were infected by the HIV. The role of the latter in the bone necrosis is questionable.

Adult