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Higher Viral Load Predicts Thromboembolism in People With HIV
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International Workshop on HIV and Aging, September 23-24, 2021
By Mark Mascolini for NATAP and Virology Education
Higher HIV load figured by three methods predicted venous thromboembolism in a study of 20,276 US residents with HIV [1]. These significant predictions held true if the analyses considered only pulmonary embolism.
Research has linked higher viral load to arterial cardiovascular disease, but researchers who conducted the new analysis noted that results of studies on HIV load and venous thromboembolism have been "mixed and limited" [2-4]. In an attempt to clarify this issue, investigators working with CNICS cohort [5] conducted this study of potential associations between HIV load level and venous thromboembolism (either deep vein thrombosis or pulmonary embolism) in HIV-positive people at sites across the United States.
CNICS is the Centers for AIDS Research Network of Integrated Clinical Systems, a prospective clinical HIV cohort with comprehensive outpatient and inpatient data. This analysis included people in care during the years 2009-2018, and diagnosis of venous thromboembolism was centrally adjudicated. The CNICS team considered viral load in three ways: baseline (with venous thromboembolism risk factors assessed by a traditional Cox proportional hazards model); time-varying (with risk factors assessed by a time-dependent Cox proportional hazards model in which variables are updated every time viral load is measured); and cumulative (figured as copy-days of virus from 6 months after CNICS enrollment, with risk factors assessed by a time-dependent marginal structural model using pooled logistic regression). Variables considered in these statistical models were age, sex, race/ethnicity, CNICS site, nadir (lowest ever) CD4 count, smoking status, diabetes, treated hypertension, and statin use.
Through a median 3.9 years of follow-up, venous thromboembolism developed in 317 of 20,276 people, including 147 people with pulmonary embolism. People with venous thromboembolism were similar to those without in proportion of women (22% and 19%), median baseline (initially measured) viral load, and cumulative viral load (7 and 6 copy-days per 10,000 days). Compared with people with venous thromboembolism, those with thromboembolism were older (median 47 vs 44 years), had a lower nadir CD4 count (169 versus 238 cells), and were more likely to smoke (40% vs 30%), have diabetes (11% vs 7%), have treated hypertension (29% vs 20%), and use statins (20% vs 14%).
Statistical analyses assessing the impact of a higher viral load on risk of venous thromboembolism compared the 75th percentile of the group viral load distribution (representing a higher viral load) with the 25th percentile (representing a lower viral load). The cumulative viral load analysis determined that people with a higher viral load had nearly a 50% greater risk of venous thromboembolism than people with a lower viral load (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.21 to 1.79, P < 0.001). A higher viral load also independently boosted risk of venous thromboembolism in the time-varying viral load analysis (aHR 1.10, 95% CI 1.05 to 1.14, P < 0.001) and in the baseline viral load analysis (aHR 1.21, 95% CI 1.10 to 1.34, P < 0.001).
The greater risk of venous thromboembolism with a higher viral load held true when the CNICS investigators limited the analysis to people with pulmonary embolism: for cumulative viral load aHR 1.49, 95% CI 1.13 to 1.96, P = 0.004; for time-varying viral load aHR 1.09, 95% CI 1.03 to 1.16, P = 0.003; and for baseline viral load aHR 1.30, 95% CI 1.12 to 1.49, P < 0.001.
The researchers noted that in both the overall analysis and the pulmonary embolism analysis, cumulative viral load proved the strongest predictor of venous thromboembolism. This robust association, they argued, is "consistent with an impact of cumulative damage from long-term or historically higher viral load, rather than high viral load as an instantaneous trigger for venous thromboembolism." That interpretation underlines the importance of "early and consistent use of antiretroviral therapy . . . to realize the full benefits of suppressing HIV replication on venous thromboembolism risk."
References
1. Ruderman S, Ma J, Delaney J, et al. High HIV viral load is associated with incident venous thromboembolism. International Workshop on HIV and Aging, September 23-24, 2021. Abstract 1.
2. Rasmussen LD, Dybdal M, Gerstoft J, et al. HIV and risk of venous thromboembolism: a Danish nationwide population-based cohort study. HIV Med. 2011;12:202-210. doi: 10.1111/j.1468-1293.2010.00869.x.
3. Bibas M, Biava G, Antinori A, et al. HIV-associated venous thromboembolism. Mediterr J Hematol Infect Dis. 2011;3:e2011030. doi: 10.4084/MJHID.2011.030.
4. Saif MW, Bona R, Greenberg B. AIDS and thrombosis: retrospective study of 131 HIV-infected patients. AIDS Patient Care STDS. 2001;15:311-320. doi: 10.1089/108729101750279687.
5. CFAR Network of Integrated Clinical Systems (CNICS). https://sites.uab.edu/cnics/
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