       Document 0006
 DOCN  M9640006
 TI    A meta-analysis of the relative efficacy and toxicity of Pneumocystis
       carinii prophylactic regimens.
 DT    9604
 AU    Ioannidis JP; Cappelleri JC; Skolnik PR; Lau J; Sacks HS; Division of
       Geographic Medicine and Infectious Diseases, New; England Medical Center
       Hospitals, Boston, Mass, USA.
 SO    Arch Intern Med. 1996 Jan 22;156(2):177-88. Unique Identifier : AIDSLINE
       MED/96135999
 AB    BACKGROUND: Finding the optimal strategy for Pneumocystis carinii
       prophylaxis in patients with human immunodeficiency virus infection can
       be problematic. Several prophylactic regimens are available, but their
       relative efficacy and tolerance are not well understood. METHODS: A
       meta-analysis overviewed 35 randomized trials comparing different
       regimens for P carinii prophylaxis directly or with placebo. Analyses
       were based on intention-to-treat. On-treatment data were also analyzed
       when available. RESULTS: Regardless of dose,
       sulfamethoxazole-trimethoprim was almost universally effective for
       patients who tolerated it. The risk of discontinuing
       sulfamethoxazole-trimethoprim because of side effects decreased by 43%
       (95% confidence interval, 30% to 54%) if one double-strength tablet was
       given three times a week instead of daily. For dapsone, among 100
       patients given 100 mg daily instead of twice a week for 1 year (primary
       prophylaxis), seven fewer patients would develop P carinii pneumonia,
       but 17 more would have significant toxic reactions. Aerosolized
       pentamidine was well tolerated regardless of the dose used. Prophylaxis
       failures might be halved if the dose of aerosolized pentamidine were
       doubled. Compared with aerosolized pentamidine, oral regimens prevented
       73% (95% confidence interval, 57% to 82%) of toxoplasmosis events by
       on-treatment analysis, but only 33% (95% confidence interval, 12% to
       50%) by intention-to-treat. No significant difference in mortality was
       demonstrated between different regimens. CONCLUSIONS:
       Sulfamethoxazole-trimethoprim is the superior regimen, and low doses
       could improve tolerance without losing effectiveness for primary
       prophylaxis. Low doses of dapsone reduce toxic effects, but at the
       expense of some loss of efficacy. There are few data on the use of
       low-dose regimens for secondary prophylaxis. High doses of aerosolized
       pentamidine may improve the efficacy of this regimen. Aerosolized
       pentamidine is inadequate for prevention of toxoplasmosis, and
       strategies that improve the tolerance of oral regimens may increase
       effectiveness in preventing toxoplasmosis.
 DE    AIDS-Related Opportunistic Infections/MORTALITY/*PREVENTION &  CONTROL
       Dapsone/*THERAPEUTIC USE  Dose-Response Relationship, Drug  Human
       Logistic Models  Multivariate Analysis  Odds Ratio
       Pentamidine/*THERAPEUTIC USE  Pneumonia, Pneumocystis
       carinii/MORTALITY/*PREVENTION & CONTROL  Randomized Controlled Trials
       Support, U.S. Gov't, P.H.S.  Survival Analysis  Toxoplasmosis/PREVENTION
       & CONTROL  Treatment Outcome  Trimethoprim-Sulfamethoxazole
       Combination/*THERAPEUTIC USE  JOURNAL ARTICLE  META-ANALYSIS

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

