Document 0275
 DOCN  M9550275
 TI    The tolerance for zidovudine plus thrice weekly or daily
       trimethoprim-sulfamethoxazole with and without leucovorin for primary
       prophylaxis in advanced HIV disease. California Collaborative Treatment
       Group.
 DT    9505
 AU    Bozzette SA; Forthal D; Sattler FR; Kemper C; Richman DD; Tilles JG;
       Leedom J; McCutchan JA; Department of Medicine, University of California
       San Diego, La; Jolla.
 SO    Am J Med. 1995 Feb;98(2):177-82. Unique Identifier : AIDSLINE
       MED/95150090
 AB    PURPOSE: Trimethoprim-sulfamethoxazole (TMP/SMX) is the preferred agent
       for prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients with
       HIV infection, but frequent adverse events limit its usefulness.
       Intermittent dosing and supplementation with leucovorin have been tried
       in attempts to improve tolerance. We evaluated these strategies in
       persons with advanced HIV disease. METHOD: One hundred seven patients
       were enrolled. All had HIV infection, < 200 CD4+ lymphocytes per mm3,
       and no history of PCP. Fifty-two were randomized to TMP/SMX twice daily
       (BID); of these, 26 were randomized to leucovorin with each dose.
       Fifty-five patients were randomized to TMP/SMX (BID) 3 times per week;
       of these, 27 were randomized to leucovorin with each dose. All patients
       took zidovudine concurrently. RESULTS: The 24-week risk of
       discontinuation due to protocol-defined limiting toxicity was 24% with
       thrice-weekly TMP/SMX versus 42% with daily TMP/SMX (risk ratio 0.4; 95%
       CI 0.2 to 1.0). The risks of discontinuation for any reason were 41% and
       59% (risk ratio 0.4; 95% CI 0.2 to 0.8). Clinical toxicity, such as
       headache and gastrointestinal distress, accounted for the observed
       difference in tolerance between dosing regimens. The 24-week risk of
       discontinuation due to protocol-defined toxicity was 33% in both the
       leucovorin and non-leucovorin groups (risk ratio 1.1; 95% CI 0.5 to
       2.5). The risks of discontinuation for any reason were 53% and 47% (risk
       ratio 0.8; 95% CI 0.3 to 1.7). CONCLUSION: Intermittent therapy with
       TMP/SMX BID thrice weekly is better tolerated than daily BID therapy.
       Leucovorin use does not improve tolerance for chronic TMP/SMX dosing in
       AIDS, even among patients taking tablets daily.
 DE    Adolescence  Adult  AIDS-Related Opportunistic Infections/*PREVENTION &
       CONTROL/  VIROLOGY  Bone Marrow Diseases/CHEMICALLY INDUCED/*PREVENTION
       & CONTROL  Drug Administration Schedule  Drug Therapy, Combination
       Female  Human  HIV Infections/DRUG THERAPY  Leucovorin/*THERAPEUTIC USE
       Male  Pneumonia, Pneumocystis carinii/*PREVENTION & CONTROL/VIROLOGY
       Proportional Hazards Models  Support, Non-U.S. Gov't  Treatment Outcome
       Trimethoprim-Sulfamethoxazole Combination/ADMINISTRATION & DOSAGE/
       *ADVERSE EFFECTS  Zidovudine/*ADVERSE EFFECTS/THERAPEUTIC USE  CLINICAL
       TRIAL  JOURNAL ARTICLE  RANDOMIZED CONTROLLED TRIAL

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