Cumulative exposure to viremia: Methods for the implementation of standardized variables in longitudinal HIV studies

Measures of viremic exposure over time, including HIV viral copy-years or durable viremic suppression, may be more relevant measures of viral load exposure for comorbid outcomes and mortality than single time point viral load measures. However, there are many subjective decisions that go into creating a cumulative variable such as HIV viral copy-years, including the appropriate anchoring point to begin accumulating exposure, the handling of viral load levels below an assay's lower limit of detection (LLD), the handling of gaps in the viral load trajectory, and when to apply the log₁₀ transformation (before or after the accumulation calculation). Different decisions produce different values for HIV viral copy-years, and such differences could impact inferences in subsequent analyses of relationships with outcomes. In this paper, we develop several HIV viral copy-years variables that are standardized across: • Anchoring point • Handling of viral loads measured below the LLD and missing viral load measures • Application of the log₁₀ transformation. These standardized variables may be consistently used in analyses of longitudinal cohort data. We also define a supplementary dichotomous HIV viral load exposure variable that may be used in tandem, or alternatively to, the HIV viral copy-years variables.