Autonomic Neuropathy as a Predictor of Morbidity and Mortality in People Living With HIV: A Retrospective, Longitudinal Cohort Study

Background and objectives: HIV-associated autonomic neuropathy (HIV-AN) is common; however, its clinical effect is unclear. Previously, it was shown that the composite autonomic severity score is associated with markers of morbidity such as the Veterans Affair Cohort Study index. In addition, it is known that cardiovascular autonomic neuropathy due to diabetes is associated with poor cardiovascular outcomes. This study aimed to evaluate whether HIV-AN is predictive of important adverse clinical outcomes.

Method: The electronic medical records of HIV-infected participants who underwent autonomic function tests at the Mount Sinai Hospital between April 2011 and August 2012 were reviewed. The cohort was stratified into those who had no or mild autonomic neuropathy (HIV-AN [-], CASS ≤3) and those with moderate or severe autonomic neuropathy (HIV-AN [+], CASS >3). The primary outcome was a composite of the incidence of death from any cause, new major cardiovascular or cerebrovascular event, or development of severe renal or hepatic disease. Time-to-event analysis was performed using Kaplan-Meier analysis and multivariate Cox proportional hazards regression models.

Results: One hundred eleven of 114 participants had follow-up data (median follow-up for HIV-AN (-) was 94.00 months, and HIV-AN (+) was 81.29 months) and were included in the analysis. Participants were followed until March 1, 2020. The HIV-AN (+) group (N = 42) was significantly associated with the presence of hypertension, higher HIV-1 viral load, and more abnormal liver function. Seventeen (40.48%) events occurred in the HIV-AN (+) group, and 11 (15.94%) occurred in the HIV-AN (-) group. Six (14.29%) cardiac events occurred in the HIV-AN (+) group, whereas 1 (1.45%) occurred in the HIV-AN (-) group. The other subgroups of the composite outcome had a similar trend. The adjusted Cox proportional hazards model showed that the presence of HIV-AN predicted our composite outcome (HR 3.85, CI 1.61-9.20).

Discussion: These findings suggest that HIV-AN is associated with the development of severe morbidity and mortality in people living with HIV. People living with HIV with autonomic neuropathy may benefit from closer cardiac, renal, and hepatic surveillance.