Impact of antiretroviral therapy on tuberculosis incidence among HIV-positive patients in high-income countries

Julia del Amo, Santiago Moreno, Heiner C Bucher, Hansjakob Furrer, Roger Logan, Jonathan Sterne, Santiago Pérez-Hoyos, Inma Jarrín, Andrew Phillips, Sara Lodi, Ard van Sighem, Wolf de Wolf, Caroline Sabin, Loveleen Bansi, Amy Justice, Joseph Goulet, José M Miró, Elena Ferrer, Laurence Meyer, Rémonie SengGiota Toulomi, Panagiotis Gargalianos, Dominique Costagliola, Sophie Abgrall, Miguel A Hernán, HIV-CAUSAL Collaboration

Research output: Contribution to journalArticle (Academic Journal)peer-review

52 Citations (Scopus)

Abstract

BACKGROUND: The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries.

METHODS: The HIV-CAUSAL Collaboration consisted of 12 cohorts from the United States and Europe of HIV-positive, ART-naive, AIDS-free individuals aged ≥18 years with baseline CD4 cell count and HIV RNA levels followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via inverse probability weighting.

RESULTS: Of 65 121 individuals, 712 developed tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000 person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95% confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for individuals aged >50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4 cell count of <50 cells/μL. Compared with people who had not started cART, HRs differed by time since cART initiation: 1.36 (95% CI, 0.98-1.89) for initiation <3 months ago and 0.44 (95% CI, 0.34-0.58) for initiation ≥3 months ago. Compared with people who had not initiated cART, HRs <3 months after cART initiation were 0.67 (95% CI, 0.38-1.18), 1.51 (95% CI, 0.98-2.31), and 3.20 (95% CI, 1.34-7.60) for people <35, 35-50, and >50 years old, respectively, and 2.30 (95% CI, 1.03-5.14) for people with a CD4 cell count of <50 cells/μL.

CONCLUSIONS: Tuberculosis incidence decreased after cART initiation but not among people >50 years old or with CD4 cell counts of <50 cells/μL. Despite an overall decrease in tuberculosis incidence, the increased rate during 3 months of ART suggests unmasking IRIS.

Original languageEnglish
Pages (from-to)1364-72
Number of pages9
JournalClinical Infectious Diseases
Volume54
Issue number9
DOIs
Publication statusPublished - May 2012

Keywords

  • AIDS-Related Opportunistic Infections
  • Adult
  • Anti-HIV Agents
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Developed Countries
  • Drug Therapy, Combination
  • Europe
  • Female
  • HIV Infections
  • HIV Seropositivity
  • Humans
  • Immune Reconstitution Inflammatory Syndrome
  • Incidence
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis
  • Pneumocystis jirovecii
  • Pneumonia, Pneumocystis
  • RNA, Viral
  • Tuberculosis
  • United States
  • Viral Load

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