Randomized trial of dapsone and aerosolized pentamidine for the prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis

Torres, Ramón A.; Barr, Michael R.; Thorn, Michael; Gregory, Gina; Kiely, Sharon; Chanin, Edith; Carlo, Claire; Martin, Michael; Thornton, John

doi:10.1016/0002-9343(93)90352-p

Cited by 66 publications

(29 citation statements)

References 28 publications

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“…Moreover, it is the cheapest available; the monthly cost of once weekly administration is <$1. Dapsone alone (100 mg twice weekly) may also be effective as primary prophylaxis for toxoplasmic encephalitis [33], but the statistical analysis of this trial was not conclusive (P = .07, logrank test) and the percentage of seropositive patients was unknown.…”

Section: Discussionmentioning

confidence: 80%

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

Opravil

Hirschel

Lazzarin

et al. 1995

Clinical Infectious Diseases

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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/AL 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/AL; 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.Prophylaxis for opportunistic infections has had a strong impact on the management of immunosuppressed human immunodeficiency virus (HIV)-infected patients in recent years, and epidemiological data indicate that Pneumocystis carinii pneumonia (PCP) has become less frequent as a consequence of prevention [1]. Aerosolized pentamidine became available in Switzerland in 1987 and was subsequently proven effective for both primary and secondary prophylaxis for PCP in controlled trials [2,3]. Among systemic prophylactic agents, trimethoprim-sulfamethoxazole became widely used [4] and was later shown to be more effective but also more toxic than aerosolized pentamidine [5,6] nations, such as dapsone and trimethoprim [7] or pyrimethamine and sulfadiazine [8], have been used for treatment of PCP before, but sparse data exist concerning their prophylactic efficacy [9]. Only recently, the prophylactic efficacy of the combination of dapsone and pyrimethamine against PCP and toxoplasmosis was demonstrated [ 10].Since in >95% of all AIDS patients with toxoplasmic encephalitis there is serological evidence of previous infection with Toxoplasma gondii [10][11][12][13], reactivation of a latent infection is the principal pathogenetic step in the development of toxoplasmic encephalitis during immunodeficiency. Considering the increasing frequency of toxoplasmic encephalitis among AIDS-defining opportunistic infections [ 1] and the 50% seroprevalence of toxoplasma antibodies in Switzerland [14], primary prophylaxis for toxoplasmic encephalitis seems desirable and clinically important, at least for seropositive patients.The sequential inhibition of dihydrofolate reductase by pyrimethamine and of dihydropteroate sy...

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Section: Discussionmentioning

confidence: 80%

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

Opravil

Hirschel

Lazzarin

et al. 1995

Clinical Infectious Diseases

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“…Dapsone/pyrimethamine and possibly dapsone alone have already been shown to prevent toxoplasmic encephalitis in addition to being efficacious as prophylaxis for PCP [5,21,22]. Because a trend toward decreased incidence of mycobacterial diseases was observed in the present analysis, combined prophylaxis for multiple opportunistic diseases with dapsone/pyrimethamine seems feasible.…”

Section: Discussionmentioning

confidence: 66%

Dapsone/Pyrimethamine May Prevent Mycobacterial Disease in Immunosuppressed Patients Infected with the Human Immunodeficiency Virus

Opravil

Péchère

Lazzarin

et al. 1995

Clinical Infectious Diseases

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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/AL, 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 baseline 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/AL, 0 vs. 12% for those whose counts were 25-49/AL, and 7% vs. 9% for those whose counts were 50-99/AL. 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. We therefore decided to retrospectively examine the incidence of tuberculous and nontuberculous mycobacterial diseases in participants of our study to assess the prophylactic efficacy of dapsone/pyrimethamine in comparison with that of aerosolized pentamidine. The risk of tuberculosis for human immunodeficiency virus (HIV)-infected patients is Methods Study PopulationThe participants were adults with symptomatic HIV infection and/or <200 CD4 lymphocytes per AL. Persons were

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“…Moreover, they also studied the potential interactions between rifampin and TMP-SMZ and hypothesized that rifampin may reduce the efficacy of TMP-SMZ. Dapsone combined with pyrimethamine (200/75 mg once weekly) was more effective in the primary prophylaxis of TE than aerosolized pentamidine (300 mg every 4 weeks) and had the advantage of a lower cost and easier administration (Torres et al, 1993;Opravil et al, 1995). Girard and colleagues (1993) revealed dapsone plus pyrimethamine prevented first episodes of TE better, but they were more toxic than aerosolized pentamidine (42 patients discontinued dapsone plus pyrimethamine while only 3 patients stopped aerosolized pyrimethamine, p<0.001) In conclusion, primary prophylaxis was the important strategy to prevent TE occurrence in the 1990s period.…”

Section: Te During Prophylaxis Regimen Period (1990s)mentioning

confidence: 99%

Toxoplasmic Encephalitis

Sukthana¹

2011

Non-Flavivirus Encephalitis

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Randomized trial of dapsone and aerosolized pentamidine for the prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis

Cited by 66 publications

References 28 publications

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

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

Dapsone/Pyrimethamine May Prevent Mycobacterial Disease in Immunosuppressed Patients Infected with the Human Immunodeficiency Virus

Toxoplasmic Encephalitis

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