Pharmacy refill adherence compared with CD4 count changes for monitoring
Added by David Bangsberg, MD, MPH on 20 Oct 2008
Download: Bisson_paper.pdf (243.1 KB)
Summary: BACKGROUND: World Health Organization (WHO) guidelines for monitoring
HIV-infected individuals taking combination antiretroviral therapy (cART) in
resource-limited settings recommend using CD4(+) T cell (CD4) count changes to
monitor treatment effectiveness. In practice, however, falling CD4 counts are a
consequence, rather than a cause, of virologic failure. Adherence lapses precede
virologic failure and, unlike CD4 counts, data on adherence are immediately
available to all clinics dispensing cART. However, the accuracy of adherence
assessments for predicting future or detecting current virologic failure has not
been determined. The goal of this study therefore was to determine the accuracy
of adherence assessments for predicting and detecting virologic failure and to
compare the accuracy of adherence-based monitoring approaches with approaches
monitoring CD4 count changes. METHODOLOGY AND FINDINGS: We conducted an
observational cohort study among 1,982 of 4,984 (40%) HIV-infected adults
initiating non-nucleoside reverse transcriptase inhibitor-based cART in the Aid
for AIDS Disease Management Program, which serves nine countries in southern
Africa. Pharmacy refill adherence was calculated as the number of months of cART
claims submitted divided by the number of complete months between cART initiation
and the last refill prior to the endpoint of interest, expressed as a percentage.
The main outcome measure was virologic failure defined as a viral load > 1,000
copies/ml (1) at an initial assessment either 6 or 12 mo after cART initiation
and (2) after a previous undetectable (i.e., < 400 copies/ml) viral load
(breakthrough viremia). Adherence levels outperformed CD4 count changes when used
to detect current virologic failure in the first year after cART initiation (area
under the receiver operating characteristic [ROC] curves [AUC] were 0.79 and 0.68
[difference = 0.11; 95% CI 0.06 to 0.16; chi(2) = 20.1] respectively at 6 mo, and
0.85 and 0.75 [difference = 0.10; 95% CI 0.05 to 0.14; chi(2) = 20.2]
respectively at 12 mo; p < 0.001 for both comparisons). When used to detect
current breakthrough viremia, adherence and CD4 counts were equally accurate
(AUCs of 0.68 versus 0.67, respectively [difference = 0.01; 95% CI -0.06 to
0.07]; chi(2) = 0.1, p > 0.5). In addition, adherence levels assessed 3 mo prior
to viral load assessments were as accurate for virologic failure occurring
approximately 3 mo later as were CD4 count changes calculated from cART
initiation to the actual time of the viral load assessments, indicating the
potential utility of adherence assessments for predicting future, rather than
simply detecting current, virologic failure. Moreover, combinations of CD4 count
and adherence data appeared useful in identifying patients at very low risk of
virologic failure. CONCLUSIONS: Pharmacy refill adherence assessments were as
accurate as CD4 counts for detecting current virologic failure in this cohort of
patients on cART and have the potential to predict virologic failure before it
occurs. Approaches to cART scale-up in resource-limited settings should include
an adherence-based monitoring approach.
Keywords: Clinical Guidelines, Monitoring & Measurement, Publications & Research, monitoring, pharmacy refil, treatment failure, viral load
Author(s): Bisson GP, Gross R, Bellamy S, Chittams J, Hislop M, Regensberg L, Frank I,
Source: PLoS Medicine
Publication Date: May 20, 2008