Marginal structural models to assess delays in second-line HIV treatment initiation in South Africa

Julia K. Rohr, Prudence Ive, C. Robert Horsburgh, Rebecca Berhanu, Kate Shearer, Mhairi Maskew, Lawrence Long, Ian Sanne, Jean Bassett, Osman Ebrahim, Matthew P. Fox

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Background: South African HIV treatment guidelines call for patients who fail first-line antiretroviral therapy (ART) to be switched to second-line ART, yet logistical issues, clinician decisions and patient preferences make delay in switching to second-line likely. We explore the impact of delaying second-line ART after first-line treatment failure on rates of death and virologic failure. Methods: We include patients with documented virologic failure on first-line ART from an observational cohort of 9 South African clinics. We explored predictors of delayed second-line switch and used marginal structural models to analyze rates of death following first-line failure by categorical time to switch to second-line. Cox proportional hazards models were used to examine virologic failure on second-line ART among patients who switched to second-line. Results: 5895 patients failed first-line ART, and 63% switched to second-line. Among patients who switched, median time to switch was 3.4 months (IQR: 1.1-8.7 months). Longer time to switch was associated with higher CD4 counts, lower viral loads and more missed visits prior to first-line failure. Worse outcomes were associated with delay in second-line switch among patients with a peak CD4 count on first-line treatment < 100 cells/mm3. Among these patients, marginal structural models showed increased risk of death (adjusted HR for switch in 6-12 months vs. 0-1.5 months = 1.47 (95% CI: 0.94-2.29), and Cox models showed increased rates of second-line virologic failure despite the presence of survivor bias (adjusted HR for switch in 3-6 months vs. 0-1.5 months = 2.13 (95% CI: 1.01-4.47)). Conclusions: Even small delays in switch to second-line ART were associated with increased death and second-line failure among patients with low CD4 counts on first-line. There is opportunity for healthcare providers to switch patients to second-line more quickly.

Original languageEnglish (US)
Article numbere0161469
JournalPloS one
Issue number8
StatePublished - Aug 2016
Externally publishedYes

ASJC Scopus subject areas

  • General


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