Among men living with HIV, current use of testosterone therapy is associated with a heightened risk of subclinical coronary atherosclerosis progression, a team of U.S. researchers has found. That increased risk appeared to be especially pronounced when comparing new testosterone therapy users to people who had stopped taking testosterone therapy several years prior.
Key takeaways from this study:
- It involved 300 men who have sex with men (MSM) living with HIV in the U.S.
- Coronary artery calcium progression was 2.4 times more likely among new users of testosterone therapy than former users.
- Noncalcified plaque progression was 2.2 times more likely among new users of testosterone therapy than former users.
- Risk was also elevated among current users of testosterone therapy who had been taking the treatment for several years.
- This study in itself is not robust or conclusive enough to alter clinical practice.
- However, it is a reminder that people with HIV on testosterone therapy should be counseled on cardiovascular risk reduction.
Study Context: Little Knowledge About Testosterone Treatment and Risk in HIV
The association of testosterone therapy with heart risk is not a new phenomenon. As study presenter Sabina A. Haberlen, Ph.D., of the Johns Hopkins Bloomberg School of Public Health noted, prescriptions of these drugs have included a warning label since 2015 noting their potential to increase a person’s risk of heart attack or stroke. Still, the impact of testosterone treatment specifically on men living with HIV hasn’t been elucidated before now, Haberlen said, even though these men are known to use such therapies at a much higher rate than their HIV-negative peers.
So Haberlen, along with a nationwide collaboration of researchers, examined data from the seminal Multicenter AIDS Cohort Study in hopes of learning more about the relationship between HIV, testosterone therapy, and cardiovascular risk. The target group for this exploration consisted of 300 MSM living with HIV in major metropolitan areas of the U.S.
The study was presented as part of a poster discussion during the Conference on Retroviruses and Opportunistic Infections (CROI 2020) on March 9.
Study Construction: A High-Risk Group of MSM With HIV
This was a generally middle-aged study cohort, with a median age of 51. This was also a pretty diverse group; fewer than half of the participants were white. Four out of five were virologically suppressed.
Baseline cardiovascular risk was common:
- 47% of participants were taking a cholesterol-lowering medication
- 41% had a 7.5% or higher 10-year risk of atherosclerotic cardiovascular disease
- 26% were active cigarette smokers
All participants received a baseline cardiac CT angiogram between 2010 and 2013, and then a follow-up angiogram between 2015 and 2017; the median time between baseline scan and follow-up was about five years. The researchers focused specifically on progression of coronary artery calcium (CAC) and noncalcified plaque volume. They stratified their findings based on the participants’ testosterone therapy status:
- 15% reported using testosterone therapy throughout the study period (starting prior to baseline and continuing through follow-up)
- 7% began using testosterone therapy after receiving their baseline scan, and were still using it at the time of their follow-up scan
- 8% reported formerly using testosterone therapy, but stopped treatment prior to their baseline scan
- 70% reported never having used testosterone therapy
In nearly all cases, men who reported receiving testosterone therapy said they did so with a prescription; three-fourths of them said they used a gel or patch, while the rest received injections.
Study Findings: New Testosterone Therapy Users at Greatest Risk
To assess the relative risk of CAC and noncalcified plaque volume, Haberlen et al decided to set former testosterone therapy users as the control group rather than people who had never used testosterone therapy. “Because of the narrow clinical criteria or personal motivations for testosterone therapy use, only a small subset of the ‘never’ users are likely to be comparable to current users on these essential criteria, many of which may also be associated with a risk of atherosclerosis progression,” Haberlen explained.
Relative to the former users of testosterone therapy, CAC progression was found to be:
- 2.4 times more likely among new users
- 2.0 times more likely among current users
- 1.7 times more likely among “never” users
Similarly, progression of noncalcified plaque was found to be:
- 2.2 times more likely among new users
- 1.5 times more likely among current users
- 1.7 times more likely among “never” users
The relative risk findings were adjusted for numerous variables, including age, race, a number of cardiovascular risk markers, CD4 count, and viral suppression.
Haberlen also noted that low levels of total testosterone in serum (i.e., less than 300 ng/dL) at baseline—which was seen in 7% of the study participants—were independently associated with CAC progression, roughly doubling the adjusted risk. No relationship was seen between low baseline testosterone and noncalcified plaque progression. Free testosterone levels were not included in this study, but Haberlen said that future research will explore the role free testosterone plays in atherosclerosis progression among MSM living with HIV.
The full clinical relevance of these findings is uncertain, and Haberlen noted that her team “cannot rule out the possibility that these results are driven by residual differences between the groups rather than an effect of testosterone therapy itself.” However, the data are enough to suggest prudent cardiovascular risk mitigation steps for men living with HIV who are taking—or who are considering—testosterone therapy, Haberlen said. Existing guidelines can provide a pathway to these steps, which include the usual suspects such as smoking cessation and statin use.