Steven Grinspoon
Chief of Metabolic Services at Massachusetts General Hospital (MGH), Director of Nutrition Obesity Research Center at Harvard University, and Honorary Chair of Endocrinology and Metabolism at MGH. Dr. Grinspoon led the large-scale, multi-center REPRIEVE study, which is the world’s first research on primary prevention strategies for cardiovascular diseases in people living with HIV (PLWH).
Editor’s note:
With the success of highly active antiretroviral therapy (HARRT), the life expectancy of HIV-infected individuals has significantly increased in recent years. The aging problem of HIV patients has become one of the main reasons affecting the quality of life and prognosis in the post-HARRT era. From July 23-26, 2023, the 12th International AIDS Society HIV Science Conference (IAS2023) was grandly held in Brisbane, Australia. At the conference, Dr. Grinspoon delivered an excellent report on primary prevention of cardiovascular diseases for PLWH. In this article, we have conducted an in-depth interview with Dr. Grinspoon. He shared insights on the metabolic and cardiovascular impacts related to PLWH treatments and the active role of statin drugs in preventing cardiovascular diseases in PLWH, especially as HIV treatment gradually shifts to chronic disease management.
01
Infectious Disease Frontier: What impact do you believe long-term antiretroviral therapy (ART) has on PLWH regarding blood lipids, weight, and cardiovascular diseases?
Dr. Grinspoon: Past research has shown that some earlier protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors (NRTI) typically impact lipids and other metabolisms, which is concerning. With the continuous advancement of new ART, the metabolic effects on patients by these drugs have been decreasing. For instance, integrase inhibitors (INSTI) are a more modern class of drugs. Although some literature suggests its association with weight gain, especially in women, we currently lack sufficient evidence to prove that this class of drugs increases cardiovascular risk in HIV patients. Personally, I think we should be more concerned about infection-related issues in these patients, which is the main factor that may lead to cardiovascular diseases.
02
Infectious Disease Frontier: The REPRIEVE study was the first to introduce statins for primary prevention in PLWH. Can you introduce the main results of these studies? What have we learned?
Dr. Grinspoon: REPRIEVE is the world’s first large-scale clinical study on primary prevention strategies for cardiovascular diseases in PLWH. We began in 2015 and recruited 7,769 volunteers aged 40-75 from 12 countries in Asia, Europe, North America, South America, and Africa, of which more than 30% were women. All participants were on ART treatment with a CD4+ cell count of >100 cells/mL at the time of enrollment, and their risk of cardiovascular disease was low to moderate (they wouldn’t typically consider statin treatment). They were randomized into either a research group receiving 4 mg of pitavastatin daily or a placebo control group. The study results indicated that patients taking statins daily reduced their risk of major adverse cardiovascular events (MACE) by 35%, including heart attacks, strokes, and cardiovascular deaths, compared to the placebo group. The observed adverse events were similar to the general population’s experiences with statin treatment. These findings suggest that taking statins daily can reduce cardiovascular disease risk in HIV patients.
03
Infectious Disease Frontier: The REPRIEVE study mainly enrolled low-to-moderate CVD risk individuals. Does this mean you would recommend statins for primary prevention to all PLWH? Or would there be a selection of the population?
Dr. Grinspoon: That’s a great question. Personally, I believe the data from this study can at least be extended to PLWH aged 40-75 with low to moderate risks. We suggest that all patients in this age range with these risk levels can now consider statin therapy. Of course, it’s a personalized decision, and some patients might not tolerate it. Overall, our research indicates that pitavastatin can be safely used with all prescribed antiretroviral treatment regimens, with good patient tolerance. As for recommending it for PLWH under 40, it might also have positive effects, but we need research on the relevant population to confirm.
04
Infectious Disease Frontier: Some individuals in clinical settings still show intolerance to statins. Can these patients consider other alternative preventive drugs?
Dr. Grinspoon: Regarding the tolerance of statin drugs in PLWH, our research indicates that only 2% and 1% of participants experienced muscle soreness and pain, respectively. Most of these were mild, and very few participants withdrew from the study due to adverse reactions. Therefore, overall, this type of statin drug has good tolerance and can be used in conjunction with antiretroviral treatment regimens. For the few who cannot tolerate it and need to consider preventing cardiovascular diseases, they can choose other cholesterol-lowering drugs. For example, a recent new cholesterol-lowering drug, bempedoic acid, has been proven to be an option for patients intolerant to statin drugs. However, the efficacy and safety of bempedoic acid in PLWH still need to be confirmed through related clinical trials.
