A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. The Dutch AIDS Treatment Group
MM Schneider, AI Hoepelman, JK Eeftinck Schattenkerk, TL Nielsen, Y van der Graaf, JP Frissen, IM van der Ende, AF Kolsters, and JC Borleffs
BACKGROUND. Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) is recommended for patients with human immunodeficiency virus (HIV) infection if their CD4 cell counts are below 200 per cubic millimeter (0.2 x 10(9) per liter). Either aerosolized pentamidine or trimethoprim-sulfamethoxazole (co-trimoxazole) is commonly prescribed for prophylaxis, but the relative efficacy and toxicity of these agents are unknown. METHODS. We conducted a multicenter trial involving 215 HIV-infected patients with no history of PCP but with CD4 cell counts below 200 per cubic millimeter. The patients were randomly assigned to one of three regimens: aerosolized pentamidine once a month, 480 mg of trimethoprim-sulfamethoxazole once a day (80 mg of trimethoprim and 400 mg of sulfamethoxazole), or 960 mg of trimethoprim-sulfamethoxazole once a day (160 mg and 800 mg, respectively). The cumulative incidence of PCP was estimated by Kaplan-Meier survival analysis. RESULTS. After a mean follow-up of 264 days, 6 of the 71 patients in the pentamidine group had a confirmed first episode of PCP (11 percent), whereas none of the 142 patients in the two trimethoprim-sulfamethoxazole groups had PCP (P = 0.002). However, adverse events that required discontinuation of the medication were much more frequent in the trimethoprim-sulfamethoxazole groups (17 and 18 patients) than in the pentamidine group (2 patients). The adverse reactions occurred significantly sooner in the group given 960 mg of trimethoprim-sulfamethoxazole than in the group given 480 mg (mean time, 16 vs. 57 days; P = 0.02). CONCLUSIONS. For patients with HIV infection, trimethoprim-sulfamethoxazole taken once a day is more effective as primary prophylaxis against PCP than aerosolized pentamidine administered once a month, although adverse drug reactions are more frequent with trimethoprim-sulfamethoxazole.
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Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
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[Abstract][Full Text]
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[Abstract][Full Text]
Kovacs, J. A., Masur, H.
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[Full Text]
USPHS/IDSA Prevention of Opportunistic Infections,
(1999). 1999 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus. ANN INTERN MED
131: 873-908
[Full Text]
Furrer, H., Egger, M., Opravil, M., Bernasconi, E., Hirschel, B., Battegay, M., Telenti, A., Vernazza, P. L., Rickenbach, M., Flepp, M., Malinverni, R., The Swiss HIV Cohort Study,
(1999). Discontinuation of Primary Prophylaxis against Pneumocystis carinii Pneumonia in HIV-1-Infected Adults Treated with Combination Antiretroviral Therapy. NEJM
340: 1301-1306
[Abstract][Full Text]
Fishman, J. A.
(1998). Prevention of Infection Due to Pneumocystis carinii. Antimicrob. Agents Chemother.
42: 995-1004
[Full Text]
Owens, D. K., Brandeau, M. L., Sox, C. H.
(1998). Effect of Relapse to High-Risk Behavior on the Costs and Benefits of a Program to Screen Women for Human Immunodeficiency Virus. Interfaces
28: 52-74
[Abstract]
Owens, D. K., Nease, R. F. Jr, Harris, R. A.
(1996). Cost-effectiveness of HIV Screening in Acute Care Settings. Arch Intern Med
156: 394-404
[Abstract]
Ioannidis, J. P. A., Cappelleri, J. C., Skolnik, P. R., Lau, J., Sacks, H. S.
(1996). A Meta-analysis of the Relative Efficacy and Toxicity of Pneumocystis carinii Prophylactic Regimens. Arch Intern Med
156: 177-188
[Abstract]
Hirschtick, R. E., Glassroth, J., Jordan, M. C., Wilcosky, T. C., Wallace, J. M., Kvale, P. A., Markowitz, N., Rosen, M. J., Mangura, B. T., Hopewell, P. C., The Pulmonary Complications of HIV Infection Study,
(1995). Bacterial Pneumonia in Persons Infected with the Human Immunodeficiency Virus. NEJM
333: 845-851
[Abstract][Full Text]
Saah, A. J., Hoover, D. R., Peng, Y., Phair, J. P., Visscher, B., Kingsley, L. A., Schrager, L. K., the Multicenter AIDS Cohort Study, , Saah, A. J., Taylor, E., Margolick, J. B., Markham, R., McArthur, J., Farzadegan, H., Armenian, H., Graham, N., Phair, J. P., Chmiel, J. S., Cohen, B., Wolinsky, S., Detels, R., Visscher, B. R., Fahey, J. L., Giorgi, J. V., Dudley, J., Lee, M., Nishanian, P., Rinaldo, C. R. Jr, Ho, M., Kingsley, L. A., Gupta, P., Winkelstein, A., Mufloz, A., Peng, Y., Galai, N., Hoover, D. R., Nelson, K., Lisa, P. J., Su, S., Schrager, L., Kaslow, R. A., VanRaden, M. J., Seminara, D.
(1995). Predictors for Failure of Pneumocystis carinii Pneumonia Prophylaxis. JAMA
273: 1197-1202
[Abstract]
Bozzette, S. A., Finkelstein, D. M., Spector, S. A., Frame, P., Powderly, W. G., He, W., Phillips, L., Craven, D., van der Horst, C., Feinberg, J., The NIAID AIDS Clinical Trials Group,
(1995). A Randomized Trial of Three Antipneumocystis Agents in Patients with Advanced Human Immunodeficiency Virus Infection. NEJM
332: 693-699
[Abstract][Full Text]
Powderly, W. G., Finkelstein, D. M., Feinberg, J., Frame, P., He, W., van der Horst, C., Koletar, S. L., Eyster, M. E., Carey, J., Waskin, H., Hooton, T. M., Hyslop, N., Spector, S. A., Bozzette, S. A., The NIAID AIDS Clinical Trials Group,
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332: 700-705
[Abstract][Full Text]
Clumeck, N.
(1995). Primary Prophylaxis against Opportunistic Infections in Patients with AIDS. NEJM
332: 739-740
[Full Text]
Jung, A. C., Paauw, D. S.
(1994). Management of Adverse Reactions to Trimethoprim-Sulfamethoxazole in Human Immunodeficiency Virus--Infected Patients. Arch Intern Med
154: 2402-2406
[Abstract]
Turner, B. J., Hecht, F. M., Ismail, R. B.
(1994). CD4+ T-Lymphocyte Measures in the Treatment of Individuals Infected With Human Immunodeficiency Virus Type 1: A Review for Clinical Practitioners. Arch Intern Med
154: 1561-1573
[Abstract]
Osmond, D., Charlebois, E., Lang, W., Shiboski, S., Moss, A.
(1994). Changes in AIDS Survival Time in Two San Francisco Cohorts of Homosexual Men, 1983 to 1993. JAMA
271: 1083-1087
[Abstract]
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32: 12-15
[Abstract][Full Text]
Hoover, D. R., Saah, A. J., Bacellar, H., Phair, J., Detels, R., Anderson, R., Kaslow, R. A., The Multicenter AIDS Cohort Study,
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329: 1922-1926
[Abstract][Full Text]
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328: 1514-1520
[Abstract][Full Text]
Weinberger, S. E.
(1993). Recent Advances in Pulmonary Medicine- Second of Two Parts. NEJM
328: 1462-1470
[Full Text]
Tarabey, R., Schneider, M. M.E., Hoepelman, A. I.M., Borleffs, J. C.C.
(1993). Primary Prophylaxis against Pneumocystis carinii Pneumonia. NEJM
328: 1499-1499
[Full Text]
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(1993). Endocrine Effects of HIV Infection. NEJM
328: 889-890
[Full Text]
Martin, M., Cox, P., Beck, K., Beall, G.
(1993). Comparing Pneumocystis carinii Pneumonia Prophylactic Regimens-Reply. Arch Intern Med
153: 783-783
[Abstract]
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1992: 1-1
[Full Text]