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 1/2009-12/2019 within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. We examined the association of three measures of HIV viral load (VL: baseline, current, cumulative) and current CD4 count with VTE. Cumulative VL (copy-days of viremia) was estimated with a time-weighted sum using the trapezoidal rule. We modeled the association between VL and VTE using Cox proportional hazards models (marginal structural Cox models for cumulative), adjusted for demographic and clinical characteristics. We compared the 75th percentile of the VL distribution with the 25th percentile using the hazard function from the model for all PWH with a VTE and those with a pulmonary embolism (PE).

Results: During a median of 4.8 years of follow-up, 424 PWH developed VTE. In adjusted analyses, higher cumulative VL (75th percentile vs. 25th percentile), the strongest VL predictor, was associated with a 1.45-fold higher risk of VTE (95%CI:1.22-1.72). Low CD4 cell count <100 cells/mm3 was associated with higher VTE risk (HR: 4.03, 95%CI: 2.76-5.89) as compared to ≥500 cells/mm3. Findings were similar for PWH who had a pulmonary embolism (n = 189).

Conclusions: Reducing HIV VL and maintaining CD4 cell count may help mitigate VTE risk in PWH.