The effect of antiretroviral therapy on all-cause mortality, generalized to persons diagnosed with HIV in the USA, 2009-11

Int J Epidemiol. 2016 Feb;45(1):140-50. doi: 10.1093/ije/dyv352. Epub 2016 Jan 15.


Background: Although antiretroviral therapy (ART) is known to be protective against HIV-related mortality, the expected magnitude of effect is unclear because existing estimates of the effect of ART may not directly generalize to recently HIV-diagnosed persons.

Methods: In this study, we estimated 5-year mortality risks for immediate versus no ART initiation among patients (n = 12,547) in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) using the complement of adjusted Kaplan-Meier survival functions. We subsequently standardized estimates to persons diagnosed with HIV in the USA between 2009 and 2011, who were enumerated using national surveillance data.

Results: The 5-year mortality, had all patients in the CNICS immediately initiated ART, was 10.6% [95% confidence interval (CI): 9.3%, 11.9%] compared with 28.3% (95% CI: 19.1%, 37.5%) had ART initiation been delayed at least 5 years. The 5-year mortality risk difference due to ART among patients in the CNICS was -17.7% (95% CI: -27.0%, -8.4%). Based on methods for generalizing an estimate from a study sample to a different target population, the expected risk difference due to ART initiation among recently HIV-diagnosed persons in the USA was -19.1% (95% CI: -30.5%, -7.8%).

Conclusions: Immediate ART initiation substantially lowers mortality among persons in the CNICS and this benefit is expected to be similar among persons recently diagnosed with HIV in the USA. We demonstrate a method by which concerns about generalizability can be addressed and evaluated quantitatively.

Keywords: HIV; antiretroviral therapy; effect modification; external validity; generalizability; mortality; survival analysis.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Female
  • HIV Infections / drug therapy*
  • HIV-1
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Mortality*
  • RNA, Viral / blood*
  • Treatment Outcome
  • United States / epidemiology
  • Young Adult


  • RNA, Viral