Analyzing Longitudinally Collected Viral Load Measurements in Youth With Perinatally Acquired HIV Infection: Problems and Possible Remedies

Abstract

Human immunodeficiency virus (HIV) viral load (VL) is an important quantitative marker of disease progression and treatment response in people living with HIV infection, including children with perinatally acquired HIV. Measures of VL are often used to predict different outcomes of interest in this population, such as HIV-associated neurocognitive disorder. One popular approach to summarizing historical viral burden is the area under a time-VL curve (AUC). However, alternative historical VL summaries (HVS) may better answer the research question of interest. In this article, we discuss and contrast the AUC with alternative HVS, including the time-averaged AUC, duration of viremia, percentage of time with suppressed VL, peak VL, and age at peak VL. Using data on youth with perinatally acquired HIV infection from the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, we show that HVS and their associations with full-scale intelligence quotient depend on when the VLs were measured. When VL measurements are incomplete, as can be the case in observational studies, analysis results may be subject to selection bias. To alleviate bias, we detail an imputation strategy, and we present a simulation study demonstrating that unbiased estimation of a historical VL summary is possible with a correctly specified imputation model.

Keywords: HIV; bias; imputation; missing data; viral load; viremia copy-years; youth.

© Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Figures

Figure 1

Distribution of log10(viral load) by age and number of youth living with perinatal human immunodeficiency virus (HIV) infection with at least 1 age measurement, Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, United States, 2007–2016. The top and bottom of the box represent the 75th and 25th percentiles, the horizontal line inside the box represents the median, the whiskers are the 10th and 90th percentiles, and outliers are shown as circles. AIDS, acquired immunodeficiency syndrome.

Figure 2

Comparison of the imputation-based historical viral load summary (HVS) with the HVS based only on observed data for youth living with perinatal human immunodeficiency virus (HIV) infection, Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, United States, 2007–2016. AIDS, acquired immunodeficiency syndrome; AUC, area under the viral load curve; AUCt, time-averaged AUC.

Figure 3

Mean difference in full-scale intelligence quotient (FSIQ) for a 1–standard-deviation (SD) difference in the imputed historical viral load among youth living with perinatal human immunodeficiency virus (HIV) infection, varying the time spans of the viral loads, Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, United States, 2007–2016. AIDS, acquired immunodeficiency syndrome; AUC, area under the viral load curve; AUCt, time-averaged AUC; HVS, historical viral load summary.