A Comparison of Methods for Analyzing Viral Load Data in Studies of HIV Patients

Abstract

HIV RNA viral load (VL) is a pivotal outcome variable in studies of HIV infected persons. We propose and investigate two frameworks for analyzing VL: (1) a single-measure VL (SMVL) per participant and (2) repeated measures of VL (RMVL) per participant. We compared these frameworks using a cohort of 720 HIV patients in care (4,679 post-enrollment VL measurements). The SMVL framework analyzes a single VL per participant, generally captured within a "window" of time. We analyzed three SMVL methods where the VL binary outcome is defined as suppressed or not suppressed. The omit-participant method uses a 8-month "window" (-6/+2 months) around month 24 to select the participant's VL closest to month 24 and removes participants from the analysis without a VL in the "window". The set-to-failure method expands on the omit-participant method by including participants without a VL within the "window" and analyzes them as not suppressed. The closest-VL method analyzes each participant's VL measurement closest to month 24. We investigated two RMVL methods: (1) repeat-binary classifies each VL measurement as suppressed or not suppressed and estimates the proportion of participants suppressed at month 24, and (2) repeat-continuous analyzes VL as a continuous variable to estimate the change in VL across time, and geometric mean (GM) VL and proportion of participants virally suppressed at month 24. Results indicated the RMVL methods have more precision than the SMVL methods, as evidenced by narrower confidence intervals for estimates of proportion suppressed and risk ratios (RR) comparing demographic strata. The repeat-continuous method had the most precision and provides more information than other considered methods. We generally recommend using the RMVL framework when there are repeated VL measurements per participant because it utilizes all available VL data, provides additional information, has more statistical power, and avoids the subjectivity of defining a "window."

Fig 1. An example of log₁₀(VL) copies/mL collected over time from baseline (month zero) and at subsequent follow-up visits for four participants.

The triangles and squares represent the closest VL to month 24 for each of the four participants.

Fig 2. The retention in care (RIC) study distribution of each participant’s closest VL copies/mL to month 24, where zero represents month 24.

There are 551 (76.5%) participants who have their closest VL within 6 months of month 24 and 232 (32.2%) whose closest VL is within 30 days.

Fig 3. Box plots by characteristic for the participants predicted VLs at month 24 and rate of change (slope).

The shaded box represents the 25^th and 75^th percentiles, while the vertical line and diamond within the shaded box are the median and mean, respectively. The upper and lower arms, represented by vertical lines, are the 2.5 and 97.5 percentiles, and dots outside these arms are considered outliers.

Fig 4. The predicted geometric mean (GM) by characteristic using the pdf-cdf random effects model plotted on the VL and log₁₀(VL) scales.

The horizontal line is the defined level of suppression (<200 copies/mL).