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The Effect of Combination Antiretroviral Therapy Use Among HIV Positive Children on the Hazard of AIDS Using Calendar Year as an Instrumental Variable

[ Vol. 16 , Issue. 2 ]

Author(s):

Andrew Anglemyer*, Amy Sturt and Yvonne Maldonado   Pages 151 - 157 ( 7 )

Abstract:


Background: Instrumental variable (IV) analyses are a common causal inference technique used in the absence of randomized data. Combination Antiretroviral Therapy (cART) was first introduced in 1996 and calendar periods have been used as a proxy for cART use. However, cART use misclassification can bias IV analyses.

Objective: We aim to highlight the differences in the effects of antiretroviral therapy on clinical outcomes between the applications of traditional and adapted IV analysis techniques.

Methods: This study includes children with perinatal human immunodeficiency virus (HIV-1) infection followed from 1988 to 2009. We describe an application of traditional and adapted IV analysis techniques. Noncompliance adjustments were applied to correct the misclassification of cART-use. Weighting the inverse probability of calendar era, the selected covariates were performed to control for variables that may be related to both the IV and outcome.

Results: During 48,380 person-days, 78 HIV-positive children progressed to an initial stage-3- defining diagnosis or death. The Intention to Treat (ITT) rate ratio (RR) of stage-3-defining diagnosis or death comparing the pre-cART and cART eras was estimated at 2·67 (95% confidence interval (CI): 1·.47, 4·84). The IV estimator was used to adjust for cART use misclassification, yielding an IV RR of 5·42 (95% CI: 2·99, 9·83). Weighting analyses did not markedly alter the results.

Conclusion: cART use decreased progression to stage-3-defining diagnosis or death. The use of noncompliance adjustments for cART misclassification in IV analyses may provide more robust evidence of cART's effectiveness than traditional ITT analysis.

Keywords:

HIV infection, mortality, pediatrics, antiretroviral drugs, intention to treat analysis, instrumental variables analysis.

Affiliation:

Operations Research Department, Naval Postgraduate School, Monterey, CA, Pediatrics-Infectious Diseases, Stanford University, Stanford, CA, Pediatrics-Infectious Diseases, Stanford University, Stanford, CA

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