Cumulative HIV viral load and lower CD4+ cell count are associated with incident venous thromboembolism in people with HIV

Background: People with HIV (PWH) have benefited greatly from antiretroviral therapy, but face additional challenges from age-related comorbid conditions, particularly cardiovascular disease including venous thromboembolism (VTE). Little is known about the effect of HIV viremia and immunodeficiency on VTE risk in this population. Methods: We assessed incident, centrally adjudicated VTE among 21 507 PWH in care between January 2009 and December 2019 within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. We examined the association of three measures of HIV viral load (baseline, current, cumulative) and current CD4 + cell count with VTE. Cumulative viral load (copy-days of viremia) was estimated with a time-weighted sum using the trapezoidal rule. We modeled the association between viral load and VTE using Cox proportional hazards models (marginal structural Cox models for cumulative), adjusted for demographic and clinical characteristics. We compared the 75 th percentile of the viral load distribution with the 25th percentile using the hazard function from the model for all PWH with a VTE and those with a pulmonary embolism. Results: During a median of 4.8 years of follow-up, 424 PWH developed VTE. In adjusted analyses, higher cumulative viral load (75th percentile vs. 25th percentile), the strongest viral load predictor, was associated with a 1.45-fold higher risk of VTE [95% confidence interval (95% CI): 1.22–1.72]. Low CD4 + cell count less than 100 cells/μl was associated with higher VTE risk (hazard ratio: 4.03, 95% CI: 2.76–5.89) as compared to at least 500 cells/μl. Findings were similar for PWH who had a pulmonary embolism ( n = 189). Conclusion: Reducing HIV viral load and maintaining CD4 + cell count may help mitigate VTE risk in PWH.