Young adults with HIV have high prevalence of heart disease risk factors

Young people living with perinatally acquired HIV have a high prevalence of metabolic complications such as diabetes and raised cholesterol and require closer monitoring for long-term cardiovascular risk, a study of young adults in the United States has found.

Although rates of perinatally acquired HIV have been falling for several decades around the world, approximately 2.5 million children and adolescents were estimated to be living with HIV in 2022, 90% in Africa and most with perinatally acquired HIV.

By the time young people with HIV reach their 20s, they may have been on ART for two decades, and may have been exposed to older, more toxic antiretrovirals. Metabolic disorders caused by antiretroviral treatment such as raised cholesterol and triglycerides may develop before adulthood, long before these conditions might be expected to emerge in the general population.

The North American AIDS Cohort Collaboration (NA-ACCORD) assessed the incidence of comorbidities that contribute to the development of cardiovascular disease between 2000 and 2019 in 375 young people aged 18 to 30 with perinatally acquired HIV. The median age at enrolment was 22 and participants were followed for median of three years. Most participants were taking a protease inhibitor (54%) or an integrase inhibitor (39%) at study entry.

In an article published recently in the journal AIDS, they reported that 19% of young people had developed diabetes by the age of 30, 40% had elevated cholesterol, 50% had elevated triglycerides, 22% had high blood pressure and 25% had chronic kidney disease (defined as an eGFR <90 for at least three months) by the age of 30. One in five had already developed elevated cholesterol or triglycerides by the time they transitioned to adult care at the age of 18.

The incidence of type 2 diabetes in this cohort was between three and six times higher than observed in young adults in North America and in older people with HIV, while the incidence of high blood pressure was 50% higher than in young adults without HIV.

The prevalence of chronic kidney disease in young people with HIV was four times higher than the prevalence in older people with HIV.

The study also found differences by race and sex. The cumulative incidence and incidence rates of type 2 diabetes were highest in Black males and non-Black females, whereas the cumulative incidence and incidence rates of elevated cholesterol and triglycerides were highest in non-Black females. One-third of Black males and females developed high blood pressure by the age of 30 compared to 4% of non-Black females and the pattern was similar for chronic kidney disease. Thirty-seven percent of Black males had developed chronic kidney disease by the age of 30, compared to 17% of non-Black females.

These remarkably high levels of metabolic comorbidity in young people with perinatally acquired HIV have yet to translate into higher rates of cardiovascular events such as heart attacks and strokes. In a symposium presentation at the recent Conference on Retroviruses and Opportunistic Infection (CROI 2024) in Denver, Dr Sahera Dirajlal-Fargo of Lurie Children's Hospital, Chicago, explored how HIV physicians should respond to these cardiometabolic warning signs in young adults with perinatally acquired HIV.

She illustrated the worrying implications of studies showing high levels of metabolic comorbidities by drawing on data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, which is tracking the relationship between risk factors and heart disease in 5,000 men and women who were aged 18 to 30 around 1985.

The Pathological Determination of Atherosclerosis in Youth (PDAY) score measures subclinical atherosclerosis, using a combination of non-HDL and HDL cholesterol, hypertension, obesity in men, age and smoking. In the CARDIA study, a score above 1 in the study’s population of 18-30 year-olds without HIV was associated with an increased risk of cardiovascular disease 25 years later. Studies of young people with HIV have shown that between 30% and 48% have a PDAY score above 1, she noted.

But more research is needed to understand the extent of the risk – and how to reduce it.

In the absence of clinical events such as heart attack, what are the best markers for monitoring the cardiovascular health of young people with perinatally acquired HIV? Do cholesterol and triglycerides provide enough information to highlight which young people have higher risks of heart disease and diabetes?

Dr Dirajlal-Fargo highlighted several measures that may provide researchers with more information.

Small differences in carotid intima media thickness between young people with and without HIV in studies to date should not be dismissed. Even a difference of 0.1mm is associated with a 15% - 18% increased risk of heart attack or stroke respectively.

A new technique for assessing cardiovascular disease, MRI scanning of the heart, showed evidence of fibrosis in young people with HIV on antiretroviral treatment in South Africa. Fibrosis in the heart tissue is a sign of injury and may eventually lead to problems such as heart failure or arrhythmia, even if no symptoms are detectable at the time of the MRI scan.

Most young people with perinatally acquired HIV are in southern and eastern Africa but most of the research on the cardiometabolic health of this population has been carried out in cohorts in North America and Europe. Much more research is needed to understand cardiometabolic changes in young people with perinatally acquired HIV in Africa, said Dr Dirajlal-Fargo.

"Metabolic disorders caused by antiretroviral treatment may develop long before these conditions might be expected to emerge in the general population."

The impact of several factors also needs to be better understood. The incidence of cardiomyopathy – damage to the heart muscle that reduces the ability of the heart to pump blood – has declined greatly since the introduction of antiretroviral treatment but children who were exposed to didanosine (ddI), zidovudine (AZT) or stavudine (d4T) remain at higher risk for the condition into adulthood. It will be important to watch for signs of cardiomyopathy and track its incidence in young adults with HIV.

Weight gain on antiretroviral treatment may also have long-term implications for cardiovascular health. There is a lack of data on weight changes in young people taking integrase inhibitors. The only randomised study in this population, ODYSSEY, found no significant difference in weight gain in children or adolescents according to treatment regimen.

Dr Dirajlal-Fargo also asked whether statins ought to be prescribed as preventive treatment in young people with HIV with higher cardiovascular risk. The REPRIEVE study, which showed that preventive treatment with pitavastatin reduced cardiovascular events in people with HIV with a low-to-moderate risk by 35%, restricted recruitment to people aged 40 and over.

In the absence of clinical trial evidence, current US guidelines on preventive statin use in people with HIV recommend that under the age of 40, statin prescription should follow guidance for the general population. US 2018 guidance recommends drug therapy in young adults only when LDL cholesterol is above 4.1mmol/L (very high).