One of the biggest stories in HIV in the past year was that statins could help reduce cardiovascular disease in people with the virus. In response, treatment guidelines in the United States were quickly updated, but the picture is more complicated in South Africa.
Spotlight’s Elri Voigt explores why the case for widespread use of statins by people with HIV is less compelling in South Africa than in some other countries.
HIV+ people, provided they are stable on antiretroviral therapy, are affected by the same diseases as those who don’t have HIV, including cardiovascular disease, says Professor Mpiko Ntsekhe, head of Cardiology at Groote Schuur Hospital.
The key difference is that although both groups get the same spectrum of diseases, people with HIV get them more frequently and earlier.
And these differences can be substantial. Current evidence shows that people with HIV have a twofold increased risk of developing CVD than those without it, says Professor Hans Strijdom, Head of the Division of Medical Physiology and Deputy Director of the Centre for Cardio-Metabolic Research in Africa (CARMA) at Stellenbosch University.
The cardiovascular risk attributable to HIV, he adds, is now believed to be equivalent to traditional risk factors such as smoking.
People with HIV who are stable on treatment are living longer, making them susceptible to the normal risk posed by older age. They also have “modifiable risk or lifestyle risk factors”, like a higher smoking and alcohol use incidence, as well as increasing rates of being overweight and obesity.
Being HIV+, even when someone is stable on treatment, causes low-grade inflammation, which over time increases the risk for CVD.
Important study findings
Arguably, the biggest news from last year’s International Aids Society (IAS) Conference in Australia was findings from a study on heart disease in people with HIV. Called REPRIEVE, it showed that the class of cholesterol-busting drugs called statins can help prevent cardiovascular disease events in people with HIV whose CVD risk score meets a certain threshold.
The findings indicated that compared with placebo, daily treatment with 4mg oral pitavastatin – a specific statin – led to a 35% reduction in major adverse cardiovascular events (MACE) in HIV patients classified to be at risk of CVD.
The study’s principal investigator, Dr Steven Grinspoon, said that while the researchers still have to assess more of the data to get a clearer picture of the mechanisms driving cardiovascular disease across regions and conduct additional sub-group analyses, the research has already shown that pitavastatin can save lives.
These sub-group analyses were discussed in greater detail at the Conference on Retroviruses and Opportunistic Infections (CROI) in Denver in March this year. For the most part, the use of pitavastatin in the manner prescribed by REPRIEVE was considered a huge success, and the US has since changed its guidelines to include the use of statins in the primary prevention of atherosclerotic cardiovascular disease.
Why it’s different in South Africa
For low-and-middle-income countries like South Africa, however, the case for pitavastatin might not be as clear-cut. In fact, a panel discussion at CROI was dedicated to exploring the implications of the REPRIEVE findings for such countries.
Ntsekhe, who was a speaker on the CROI panel, said that data from REPRIEVE’s sub-group analyses reveal a striking difference in event rates – which in the case of the study are MACE in those who were getting the placebo – by country income status. He says that as predicted in high-income countries, the event rates were high, while in low-and-middle income countries, particularly in Sub-Saharan Africa (SSA), event rates were very low.
One of the reasons was that the screening tool used in REPRIEVE worked well to identify those people with HIV who might benefit from pitavastatin in high-income countries like the United States, but it did not work well in SSA.
This means using pitavastatin as part of a primary prevention strategy is a much more effective intervention in high-income countries than in low-and-middle income countries because the CVD profile is so different.
Ntsekhe says the term cardiovascular disease itself is broad and all-encompassing and there are many forms, including valve disease, heart muscle disease, and vascular disease. The dominant form of CVD in the high-income countries (the Global North) is atherosclerotic cardiovascular disease, characterised by a build-up of fatty deposits and plaque in the arteries.
In SSA though, “atherosclerotic cardiovascular disease is but one of many forms of cardiovascular disease”, taking fourth or fifth place in the rankings.
Studies in high-income countries don’t always take differences in disease burden into account, according to Ntsekhe. This means those interventions shown to be effective in that context won’t necessarily work as well in countries like South Africa.
Strijdom concurs that while results from REPRIEVE in the global context were a game-changer, the findings are not easily transferable to South Africa’s context because pitavastatin is mainly aimed at reducing “bad cholesterol” and coronary artery disease (atherosclerosis).
‘Taking money away’
During the panel discussion at CROI, Ntsekhe asked whether Sub-Saharan Africa could justify taking money away from other health programmes that work to invest in pitavastatin.
“I said what should be a priority for us is tools that can better identify those at risk, and continuing to focus on what our local data suggests are the priority areas,” Ntsekhe says.
“REPRIEVE was a wonderful study: the hypothesis was tested, and it was shown to be correct, the intervention we know works. It really then comes down to regional areas, to think carefully about how best they’re going to get their biggest bang for their buck. We have to carefully consider the local context, local burden… and weigh benefit and cost before adopting new interventions or recommendations.”
SA’s cardiovascular disease burden
While Strijdom says we don’t have great data, he points to a large systematic review and meta-analysis published in 2018 in Circulation, estimating that around 15% of the total CVD burden in South Africa is attributable to HIV. “It’s probably higher than that. I would say that probably about one in five people in this country with heart disease have heart disease because of HIV,” he says, “and that figure is only going to increase”.
Because of this, there is a need for proper and clear primary healthcare guidelines “specifically aimed at managing CVD in people living with HIV, which we don’t currently have”.
What we have at the moment since the rollout of the 2019 National ART Clinical Guidelines is very basic guidelines, he adds. This involves screening someone who has just been diagnosed with HIV by taking their blood pressure, and testing urine for glucose and proteins, and an assessment of their general cardiovascular disease risk by taking their medical and family history.
He says these guidelines only make provision for routine screening at baseline, but screening guidelines at follow-up visits are insufficient.
“I am, however, aware that there is progress, especially from the integrated chronic disease management model currently being piloted in South Africa – and hopefully with that will come more definitive and universal guidelines. The bottom line is that South Africa, in its public health [sector] especially, really very quickly needs to come up with clear and more comprehensive guidelines to actively manage CVD risk in people with HIV.”
Need for annual screening
Strijdom suggests that to improve screening for CVD risk in HIV+ people, there needs to be annual screening of their weight, measure of body fat based on height and weight, waist circumference, blood pressure, cholesterol and triglyceride levels as well as testing urine samples for kidney function. There also needs to be a thorough family and medical history conducted.
“It’s not a very expensive or exhaustive list… unless they have specific symptoms and signs leading you in a specific direction that you then have to perhaps do an ECG or cardiac imaging, but that is usually determined by what you get from their history and clinical examination,” he says.
Ntsekhe says public health strategies to combat the growing burden of non-communicable diseases (NCDs), including CVD, must be strengthened. These include screening and prevention tools like checking BP and blood glucose, advising against smoking and alcohol as well as promoting healthy lifestyle choices like exercise and weight loss. These interventions should be offered to everyone, regardless of whether they have HIV or not, he says.
“The thing about NCDs and cardiovascular disease, for the most part, they are diseases of lifestyle and behaviour. So, when you talk prevention, it’s not always about drug prevention. It’s more about intensification of those [interventions] that are already in the public domain, are effective, and cheap.”
Stritjdom says people need to be aware of issues like high blood pressure.
“Our health system is understandably focused on infectious diseases, but if we are not careful, we will be totally unprepared to tackle the epidemic that will have replaced it – cancer, heart disease, stroke, obesity, diabetes, which will totally overwhelm our public healthcare system.”
See more from MedicalBrief archives:
Statins slash CVD risk in people with HIV – global study
Fewer people may need statins to prevent heart disease – US study
Statin treatment and exercise benefits for HIV-positive people
Don’t panic, say experts as HIV drug flagged for resistance