A randomized trial of punctuated antiretroviral therapy in Ugandan HIV-seropositive adults with pulmonary tuberculosis and CD4⁺ T-cell counts of ≥ 350 cells/μL

J Infect Dis. 2011 Sep 15;204(6):884-92. doi: 10.1093/infdis/jir503.

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Antiretroviral Therapy, Highly Active / methods*
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / adverse effects
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • Dideoxynucleosides / administration & dosage
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / mortality
  • Humans
  • Lamivudine / administration & dosage
  • Male
  • Middle Aged
  • Survival Analysis
  • Treatment Outcome
  • Tuberculosis, Pulmonary / complications
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / mortality
  • Uganda
  • Young Adult
  • Zidovudine / administration & dosage

Substances

  • Anti-HIV Agents
  • Antitubercular Agents
  • Dideoxynucleosides
  • Lamivudine
  • Zidovudine
  • abacavir