Once-weekly administration of dapsone/pyrimethamine vs. aerosolized pentamidine as combined prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis in human immunodeficiency virus-infected patients.

To evaluate combined prophylaxis for Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis, 533 patients with symptomatic human immunodeficiency virus infection and/or CD4 lymphocyte counts of < 200/microL were randomized to receive dapsone/pyrimethamine (200/75 mg once weekly) or aerosolized pentamidine (300 mg every 4 weeks). The median CD4 lymphocyte count was 110/microL; 47.5% were seropositive for toxoplasma antibodies. The median duration of follow-up was 483 days. In the intent-to-treat analysis, 12 cases of PCP and 14 of toxoplasmic encephalitis occurred in the dapsone/pyrimethamine group and 13 and 20 cases, respectively, in the aerosolized pentamidine group (adjusted relative risk for toxoplasmosis, 0.56; P = .10). However, only two of the 14 cases of toxoplasmic encephalitis in the dapsone/pyrimethamine group developed during actual treatment. The mortality among the two groups was similar. Dapsone/pyrimethamine was not tolerated by 30% of participants. A subanalysis of 240 matched, tolerant patients yielded a relative risk for toxoplasmosis of 0.21 (P = .014), a result favoring the use of dapsone/pyrimethamine. Dapsone/pyrimethamine was as effective as aerosolized pentamidine as prophylaxis for PCP and significantly reduced the incidence of toxoplasmic encephalitis among those participants who tolerated it.

Dapsone/pyrimethamine may prevent mycobacterial disease in immunosuppressed patients infected with the human immunodeficiency virus.

Dapsone exhibits activity against Mycobacterium tuberculosis and Mycobacterium avium complex (MAC) in vitro. We retrospectively examined the incidence of mycobacterial diseases within a randomized prospective trial of prophylaxis for Pneumocystis carinii pneumonia and toxoplasmosis. Of 501 participants who had not previously had a mycobacterial disease, 274 received dapsone/pyrimethamine (200/75 mg once weekly) and 227 received aerosolized pentamidine (300 mg once every 4 weeks). The median CD4 lymphocyte count was 113/microL, and the median duration of treatment was 369 days. Six cases of tuberculosis, 22 of MAC infection, and 3 of Mycobacterium genavense disease occurred during treatment. Stratified by basement CD4 lymphocyte counts, the annual product-limit incidence of mycobacterial disease was 5% during treatment with dapsone/pyrimethamine vs. 12% during treatment with aerosolized pentamidine for patients whose counts were 0-24/microL, 0 vs. 12% for those whose counts were 25-49/microL, and 7% vs. 9% for those whose counts were 50-99/microL. Adjusted for CD4 lymphocyte counts at start of treatment, the relative risk for patients receiving dapsone/pyrimethamine was 0.47 (95% confidence interval, 0.19-1.16; P = .10). This inexpensive and simple regimen may prevent mycobacterial diseases and warrants further investigation as a means of prophylaxis for multiple opportunistic diseases.

[True aneurysm of the ascending aorta in HIV disease]. / Aneurysma verum der Aorta ascendens im Rahmen einer HIV-Krankheit.

A 31-year-old male who presented with a true aneurysm of the ascending aorta had for 5 years been seropositive for HIV-1 following intravenous drug abuse. Elective aneurysmectomy was refused. Controls by computerized tomography and echocardiography gave evidence of a progressive dilatation during the following 8 months. In February 1992 a further increase of the aneurysm with severe thoracic pain necessitated an emergency graft implantation. Histopathology of the resected aorta revealed a granulomatous giant cell mesaortitis. The postoperative course was uneventful and the patient remained free of cardiovascular symptoms, but died 25 months later due to multiple HIV-associated opportunistic infections. The differential diagnosis (Marfan's syndrome, vasculitis due to tuberculosis, syphilis and other infectious agents, rheumatological diseases, HIV-associated vasculitis) and the etiopathological considerations are discussed.

[HIV prevention in HIV-positive drug addicts. A methadone-supported model]. / HIV-Prävention bei HIV-positiven Drogenabhängigen. Ein methadongestütztes Modell.

In Switzerland, an estimated 15-25% of intravenous drug users (IVDUs) are infected with human immunodeficiency virus (HIV). It has been suggested that reduction of HIV-transmission-prone behavior could be achieved in so-called "early intervention programs". Few public prevention programs have so far been targeted to HIV-infected IVDUs. Socially marginalized, jobless, street-based, HIV-infected IVDUs are those hardest to reach for education programs: it was the hypothesis that they can be motivated for HIV-prevention efforts by methadone-based comprehensive social and medical care. The program was established by integrating one additional social worker in an outpatient clinic for infectious diseases in St. Gallen, a city with a population of 70,000 inhabitants in eastern Switzerland. Access to the 29 clients of this study (10 women, 19 men) was facilitated by offering methadone treatment (follow-up 5 to 29 months). Abstinence from additional illegal drugs was not required. Methadone, plus social care and medical treatment was provided by a small team consisting of a social worker, a physician and a nurse. A gradual approach was chosen to establish a working relationship with clients. The first attempt was to satisfy basic medical needs, housing, and financial support as well as to strengthen relevant personal relationships. Once trusting cooperation was established, reduction of transmission-prone behavior was targeted. The results show that social performance can be greatly improved by integrated social, psychological and medical assistance: for the 16 initially homeless housing was found, 14 found a job and for all but 2 basic financial support was eventually guaranteed. Self-reported drug abuse was markedly reduced, as was transmission-prone behavior by prostitution, unsafe sex practices, needle sharing and improper disposal of used syringes. Breaking the isolation of socially marginalized IVDUs seems to be the important move to enhance their social responsibility as carriers of HIV.

[Metastatic pulmonary calcification in patients with chronic renal insufficiency]. / Metastatische Lungenverkalkungen bei Patienten mit chronischer Niereninsuffizienz.

Case reports on two patients with metastatic pulmonary calcification are presented. Both suffered from long standing chronic renal failure and received immunosuppressive therapy for a (non-functioning) renal transplant. Laboratory tests disclosed hyperphosphatemia and secondary hyperparathyroidism. In the first patient, who presented with "pulmonary edema", the course was rapidly fatal. Diffuse pulmonary calcification was diagnosed only post mortem. Transbronchial biopsy was diagnostic for calcification in the second patient, who had exertional dyspnea and bilateral, asymmetric, interstitial infiltrations on chest X-ray. In patients with chronic renal failure, metastatic calcifications are due not only to disturbances of calcium-phosphate homeostasis but also to other, mostly unknown factors. Diagnostic procedures include biopsy and 99m-technetium-diphosphonate scintigraphy. Prophylaxis of pulmonary calcifications through normalization of serum phosphate and, if indicated, subtotal parathyroidectomy is of the utmost importance as regression of established calcifications rarely occurs.