Association of age with mortality and virological and immunological response to antiretroviral therapy in rural South African adults

PLoS One. 2011;6(7):e21795. doi: 10.1371/journal.pone.0021795. Epub 2011 Jul 1.


Objective: To assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART) in a large rural HIV treatment cohort.

Design: Retrospective cohort analysis using data from a public HIV Treatment & Care Programme.

Methods: Adults initiating ART 1(st) August 2004-31(st) October 2009 were stratified by age at initiation: young adults (16-24 years) mid-age adults (25-49 years) and older (≥50 years) adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points.

Results: 8846 adults were included, 808 (9.1%) young adults; 7119 (80.5%) mid-age adults and 919 (10.4%) older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004) compared to those aged 25-49 years. Overall mortality rates (MR) per 100 person-years were 6.18 (95% CI 4.90-7.78); 6.55 (95% CI 6.11-7.02) and 8.69 (95% CI 7.34-10.28) for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0-3 months (MR: 27.1 vs 17.17 and 21.36) and 3-12 months (MR: 9.5 vs 4.02 and 6.02) respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1 year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0-3 months) whilst immunological and virological responses were associated with mortality after 12 months.

Conclusions: Early ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly in the initial phases of ART.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / mortality*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / pathogenicity
  • Humans
  • Male
  • Middle Aged
  • Rural Population / statistics & numerical data*
  • South Africa
  • Treatment Outcome
  • Young Adult


  • Anti-HIV Agents