title: Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death.
abstract: Ninety-two AIDS patients with Pneumocystis carinii pneumonia (PCP) were randomized to receive folinic acid or matching placebo in conjunction with trimethoprim-sulfamethoxazole in a prospective, double-blind trial. Neither frequency of dose-limiting toxicity (26% vs. 37%; P = .4) nor time to occurrence (P = .7) was associated with folinic acid use. Although incidence of neutropenia was lower in patients receiving folinic acid (23% vs. 47%; P = .03), time to occurrence of neutropenia did not differ (P = .4). Seven (7.6%) of 92 patients with confirmed PCP met criteria for therapeutic failure, and 5 (6%) died during therapy. Surprisingly, folinic acid use was associated with a higher rate of both therapeutic failure (15% vs. 0; P = .01) and death (11% vs. 0; P = .06). Time to therapeutic failure was shorter and probability of death greater in patients receiving folinic acid (P = .005, P = .02, respectively), even when adjusted for baseline arterial oxygen pressure, serum lactate dehydrogenase, respiratory rate, CD4 cell count, and peak serum level of trimethoprim or sulfamethoxazole.
authors.affiliation: Department of Medicine, University of California, San Francisco.
authors.forename: S
authors.initials: S
authors.lastname: Safrin
authors.forename: B L
authors.initials: BL
authors.lastname: Lee
authors.forename: M A
authors.initials: MA
authors.lastname: Sande
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000401:mortality; D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D015994:Incidence; D002955:Leucovorin / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000453:epidemiology; D010919:Placebos; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000401:mortality; D011336:Probability; D012307:Risk Factors; D017211:Treatment Failure; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
chemical_list: D010919:Placebos; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D002955:Leucovorin