title: Efficacy of trimethoprim-sulfamethoxazole for the prevention of bacterial infections in a randomized prophylaxis trial of patients with advanced HIV infection.
abstract: We compared the occurrences of several types of infections in HIV-infected patients participating in a randomized clinical trial of three treatment strategies given for the primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis. In a phase III open label trial, 842 patients with HIV infection and fewer than 200 CD4+ cells/mm(3) received zidovudine (standard dose) plus one of three randomly assigned prophylactic agents: trimethoprim-sulfamethoxazole (TMP-SMZ), or dapsone (DAP), or aerosolized pentamidine (AP). Patients developing intolerance to treatment were crossed over to another predefined prophylactic therapy. Patients were monitored for infections every other week for 8 weeks and then monthly until the study was completed. Primary statistical models were proportional hazards models adapted to recurrent end points. In an intent-to-treat analysis, compared with AP and DAP, TMP-SMZ significantly reduced the risk of any bacterial infection (combining all distinct types) (p = 0.02 and p = 0.01, respectively). When considering distinct types separately, compared with AP, TMP-SMZ significantly reduced the risk of infectious diarrhea (p = 0.04); compared with DAP, AP and TMP-SMZ significantly reduced the risk of sinusitis/otitis media (p = 0.03 and p = 0.04, respectively); compared with AP and DAP, TMP-SMZ significantly reduced the risk of a second occurrence of pneumonia (p = 0.04 and 0.02, respectively). For any bacterial infection, infection rates per 100 patient-years of follow-up were 31, 39, and 38 for TMP-SMZ, DAP, and AP, respectively. In patients with advanced HIV infection not taking highly active antiretroviral therapy, the treatment strategy that initiates prophylaxis with TMP-SMZ is superior to those initiating with AP or DAP for preventing any bacterial infection, with most of the advantage manifested through infectious diarrhea, sinusitis/otitis media, and pneumonia.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. dirienzo@sdac.harvard.edu
authors.forename: A Gregory
authors.initials: AG
authors.lastname: DiRienzo
authors.forename: Charles
authors.initials: C
authors.lastname: van Der Horst
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Finkelstein
authors.forename: Peter
authors.initials: P
authors.lastname: Frame
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Bozzette
authors.forename: Karen T
authors.initials: KT
authors.lastname: Tashima
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology / Q000517:prevention & control*; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000150:complications / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D012044:Regression Analysis; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination