Testosterone therapy linked to faster progression of atherosclerosis in men with HIV

Men living with HIV who receive testosterone therapy experience faster progression of atherosclerosis, the silent process of damage that precedes a heart attack or other serious cardiovascular event, a study of gay and bisexual men in the Multicenter AIDS Cohort study (MACS) has found.

The findings were presented to the virtual Conference on Retroviruses and Opportunistic Infections (CROI 2020) on Monday. (All CROI 2020 presentations are taking place on the internet to minimise the risk of coronavirus transmission.)

Studies of cardiovascular risk in men have linked both testosterone therapy and low levels of testosterone to an increased risk of cardiovascular disease. However, a recently published review of general population studies concluded that there was no increased risk of cardiovascular events for men who received testosterone replacement therapy.

None of these studies included a defined subgroup of older men living with HIV. Testosterone therapy is prescribed to older men living with HIV with testosterone deficiency who are experiencing symptoms of hypogonadism such as muscle wasting, bone mineral loss, increased abdominal fat or sexual dysfunction. A 2015 review of prescriptions for testosterone therapy showed that men with HIV in the United States were two-and-a-half times more likely to be receiving it than HIV-negative men.

To better define the cardiovascular implications of testosterone therapy in men with HIV, Dr Sabina Haberlen of Johns Hopkins University Bloomberg School of Public Health and colleagues from the MACS study compared cardiovascular disease progression in 300 men in the cohort according to testosterone therapy exposure.

Cohort participants aged 40 to 70 underwent baseline CT (computed tomography) scans between 2010 and 2013 and again between 2015 and 2017, a median interval of 4.6 years.

The study compared the progression of subclinical cardiovascular disease, defined as the development or worsening of coronary plaques and coronary artery calcium. Both contribute to an increased risk of cardiovascular events by narrowing arteries, reducing their flexibility and causing the build-up of unstable plaques on artery walls. These plaques may detach and block an artery, leading to a heart attack or stroke.

Four groups were compared:

Find out more: Coronary heart disease and HIV

• Current and ongoing users who were exposed to testosterone replacement therapy (TRT) at both scans (n = 53)
• New users, who started TRT after the first scan (n = 21)
• Former users who stopped TRT before the first scan (n = 24) (chosen as a second control as they had a prior indication for TRT)
• Men who had never used TRT (a control group, n = 211).

The groups were evenly matched in most respects except that higher proportions of current users were also at higher risk of cardiovascular events (50% had > 7.5% 10-year risk compared to 36-40% in other groups) and taking cholesterol-lowering medication (63% vs 43-52%).

Progression of plaque and coronary artery calcium was more likely to occur in new or ongoing users of testosterone therapy. Compared to former users, new users had more than twice the risk of progression (non-calcified plaque: adjusted relative risk 2.16; coronary artery calcium: aRR 2.37) after adjusting for other cardiovascular risk factors.

Ongoing users also had a higher risk of coronary artery calcium progression (aRR 1.99) but not of non-calcified plaque progression.

Low baseline testosterone levels (< 300ng/dl) were also associated with coronary artery calcium progression (aRR 1.97, p < 0.001) but not of non-calcified plaque.

The researchers say that more evidence is needed about the impact of testosterone therapy on cardiovascular risk in men living with HIV. In the meantime, cardiovascular risk reduction interventions such as smoking cessation and cholesterol-lowering medication should be implemented for men taking testosterone therapy, in line with existing guidelines for risk reduction, they say.