by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer

October 8, 2019

Featured Literature:
Beckman JA, et al Association of Human Immunodeficiency Virus Infection and Risk of Peripheral Artery Disease.

The impact of HIV infection on cardiovascular disease has been supported by physiologic, observational and clinical data. However, the effect of HIV on the development of peripheral artery disease (PAD) has not been well studied. This paper is from the Veterans Aging Cohort Study (VACS) – a prospective, longitudinal cohort of HIV-infected and uninfected veterans matched 1:2 for clinical site, year of enrollment, age, sex, and race/ethnicity. The intent was to determine if HIV infection increased the risk of PAD after adjusting for traditional risk factors such as diabetes, hypertension, hyperlipidemia, smoking, and HCV infection. Excluded were persons with known PAD or prevalent CVD (history of: MI, stroke, CAD, and CHF) at baseline. The authors included 91,953 patients, 31% who were HIV-positive. The primary outcome was incident PAD events. Secondary outcomes included amputations and mortality with incident PAD events. The authors specifically analyzed the effect of HIV status on risk of incident PAD. As with other VACS studies, they controlled for CD4+ count, HIV-RNA level and use of ART. Among subjects who were followed for a median of 9.0 years, there were 7,708 incident PAD events. Rates of incident PAD events were 11.9 per 1000 person-years in HIV+ subjects and 9.9/1000 person-years in uninfected veterans. An increased risk of PAD was seen primarily in those with time-updated HIV viral loads >500 copies/mL and CD4 cell counts <200 cells/mm3. Those HIV+ veterans with time-updated CD4 cell count ≥500 cells/mm3 had no increased risk of PAD. Mortality rates after incident PAD events were high in both HIV positive and negative veterans and amputation rates were similar in both groups. The authors believe these data support HIV infection as a risk factor for incident PAD and associated vascular events, independent of the well-established risk factors for atherosclerosis.

Author’s Commentary:

In this study from the VACS, HIV infection was associated with almost a 20% increased risk of PAD beyond that expected with traditional atherosclerotic risk factors, however this was only seen in those with persistent viremia and low CD4 cell counts. Other studies have suggested that HIV impairs vascular function, causes endothelial dysfunction and promotes systemic atherosclerosis. It is also possible that older HIV medications that led to adverse metabolic effects played a role. The exact mechanisms by which HIV increases generalized atherogenesis and specifically PAD remain unclear. As with other vascular and inflammatory conditions, effective treatment with ART appears to mitigate risk. Assessing for symptoms of PAD (e.g. claudication) and clinical evaluation for PAD in the office setting is important, especially for higher risk patients. Readers are referred to a recently published excellent review on diagnosis and management of PAD. Firnhaber JM et al, Lower Extremity Peripheral Artery Disease: Diagnosis and Treatment. Am Fam Physician. 2019; 99(6):362-369.  

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