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

Author(s): Andrew Anglemyer*, Amy Sturt, Yvonne Maldonado

Journal Name: Current HIV Research

Volume 16 , Issue 2 , 2018


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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.

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Article Details

VOLUME: 16
ISSUE: 2
Year: 2018
Published on: 15 August, 2018
Page: [151 - 157]
Pages: 7
DOI: 10.2174/1570162X16666180409150826
Price: $65

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