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Marginal Structural Models to Assess Delays in Second-Line HIV Treatment Initiation in South Africa.


ABSTRACT:

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.

SUBMITTER: Rohr JK 

PROVIDER: S-EPMC4993510 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Marginal Structural Models to Assess Delays in Second-Line HIV Treatment Initiation in South Africa.

Rohr Julia K JK   Ive Prudence P   Horsburgh C Robert CR   Berhanu Rebecca R   Shearer Kate K   Maskew Mhairi M   Long Lawrence L   Sanne Ian I   Bassett Jean J   Ebrahim Osman O   Fox Matthew P MP  

PloS one 20160822 8


<h4>Background</h4>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.<h4>Methods</h4>We include patients with documented virologic failure on first-line ART from an obser  ...[more]

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