title: A randomized trial of punctuated antiretroviral therapy in Ugandan HIV-seropositive adults with pulmonary tuberculosis and CD4⁺ T-cell counts of ≥ 350 cells/μL.
abstract: BACKGROUND
  Optimal treatment of human immunodeficiency virus (HIV)-associated tuberculosis in patients with high CD4⁺ T-cell counts is unknown. Suppression of viral replication during therapy for tuberculosis may block effects of immune activation on T cells and slow HIV disease progression.
  
  
  METHODS
  We conducted a randomized trial in 214 HIV-infected patients with active tuberculosis and CD4⁺ T-cell counts of ≥ 350 cells/μL to determine whether 6 months of antiretroviral therapy given during tuberculosis treatment would improve clinical outcomes. Subjects were randomized to receive 6 months of abacavir-lamivudine-zidovudine concurrent with tuberculosis therapy or delayed antiretroviral therapy. Endpoints were CD4⁺ T-cell counts of < 250 cells/μL, AIDS, or death.
  
  
  RESULTS
  Intervention and comparison arms had similar median CD4⁺ counts (517 and 534 cells/μL, respectively) and HIV RNA levels (4.6 and 4.7 log₁₀ copies/μL, respectively). Viral suppression was achieved in 86% of patients allocated to intervention. Seventeen subjects (15.6%) in the intervention arm developed study outcome compared to 25 subjects (22.8%) in the comparison arm (P = .17). Grade 3 or 4 adverse events were less frequent in the intervention arm. By 2 months, 90% of subjects in both arms were culture-negative for tuberculosis.
  
  
  CONCLUSIONS
  Short-term antiretroviral therapy during tuberculosis treatment in patients with CD4⁺T-cell counts of >350 cells/μL was safe and associated with clinical benefits.
authors.affiliation: Uganda-Case Western Reserve University Research Collaboration, Makerere University, Kampala, Uganda.
authors.forename: M W
authors.initials: MW
authors.lastname: Nanteza
authors.forename: H
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.forename: E
authors.initials: E
authors.lastname: Charlebois
authors.forename: P
authors.initials: P
authors.lastname: Srikantiah
authors.forename: R
authors.initials: R
authors.lastname: Lin
authors.forename: E
authors.initials: E
authors.lastname: Mupere
authors.forename: P
authors.initials: P
authors.lastname: Mugyenyi
authors.forename: W H
authors.initials: WH
authors.lastname: Boom
authors.forename: R D
authors.initials: RD
authors.lastname: Mugerwa
authors.forename: D V
authors.initials: DV
authors.lastname: Havlir
authors.forename: C C
authors.initials: CC
authors.lastname: Whalen
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015224:Dideoxynucleosides / Q000008:administration & dosage; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D014454:Uganda; D055815:Young Adult; D015215:Zidovudine / Q000008:administration & dosage; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D015224:Dideoxynucleosides; D019259:Lamivudine; D015215:Zidovudine; D000099227:Abacavir