期刊
AMERICAN JOURNAL OF EPIDEMIOLOGY
卷 184, 期 1, 页码 67-77出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/aje/kwv303
关键词
Cox proportional hazards models; HIV; human immunodeficiency virus; Martingale residuals; mortality; opportunistic infections; viral load; viremia copy-years
资金
- Infectious Diseases Institute at Makerere University (Kampala, Uganda)
- US National Institutes of Health [R25GM102149]
- James S. McDonnell Foundation
- US National Institute of General Medical Sciences MIDAS grant [U01GM087719]
- Department of Science and Technology/National Research Foundation SACEMA
Recent studies have evaluated cumulative human immunodeficiency virus type 1 (HIV-1) viral load (cVL) for predicting disease outcomes, with discrepant results. We reviewed the disparate methodological approaches taken and evaluated the prognostic utility of cVL in a resource-limited setting. Using data on the Infectious Diseases Institute (Makerere University, Kampala, Uganda) cohort, who initiated antiretroviral therapy in 2004-2005 and were followed up for 9 years, we calculated patients' time-updated cVL by summing the area under their viral load curves on either a linear scale (cVL(1)) or a logarithmic scale (cVL(2)). Using Cox proportional hazards models, we evaluated both metrics as predictors of incident opportunistic infections and mortality. Among 489 patients analyzed, neither cVL measure was a statistically significant predictor of opportunistic infection risk. In contrast, cVL(2) (but not cVL(1)) was a statistically significant predictor of mortality, with each log(10) increase corresponding to a 1.63-fold (95% confidence interval: 1.02, 2.60) elevation in mortality risk when cVL(2) was accumulated from baseline. However, whether cVL is predictive or not hinges on difficult choices surrounding the cVL metric and statistical model employed. Previous studies may have suffered from confounding bias due to their focus on cVL(1), which strongly correlates with other variables. Further methodological development is needed to illuminate whether the inconsistent predictive utility of cVL arises from causal relationships or from statistical artifacts.
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