About

Dr. Steven K. Grinspoon is a Professor of Medicine at Harvard Medical School, Chief of the Metabolism Unit at Massachusetts General Hospital, and Director of the Nutrition Obesity Research Center at Harvard. His research investigates the neuroendocrine regulation of body composition and the physiologic consequences of fat distribution on cardiovascular disease and inflammation. He has studied the effects of reduced growth hormone on metabolic dysregulation in obesity and was the first to propose the use of a GHRH analogue to increase endogenous GH secretion for lipodystrophy and generalized obesity, leading to the FDA approval of tesamorelin for excess visceral fat accumulation in HIV-infected patients. His work has extended to show robust effects on non-alcoholic fatty liver disease (NAFLD). More recently, his research focuses on the inflammatory mechanisms by which ectopic fat and other metabolic perturbations contribute to cardiovascular disease in HIV, including leading the large multicenter REPRIEVE study, the first primary prevention strategy for CVD in HIV. Additionally, he has investigated increased RAAS activation and immune activation related to visceral fat accumulation, as well as mechanisms of subcutaneous adipose dysfunction involving DICER. Dr. Grinspoon has served on the Harvard faculty since 1995 and has been recognized by the American Society for Clinical Investigation and the Association of American Physicians for his scientific contributions. He has received several awards, including the American Federation of Medical Research Investigator of the Year Award in 2005, the Edward H. Ahrens Jr. Award for Patient Oriented Research in 2014, and the Endocrine Society Laureate Award for Translational Research in 2016.

Research topics

• Medicine
• Internal medicine
• Geography
• Biology
• Environmental health
• Endocrinology
• Political Science
• Sociology
• Bioinformatics
• Virology
• Economic growth
• Gerontology
• Economics
• Intensive care medicine
• Immunology

Selected publications

• Muscle movement and metabolism: exercise and skeletal muscle as mediators of health—a report from the 26th Annual Harvard Nutrition Obesity Symposium, 2025

  American Journal of Clinical Nutrition · 2026-03-09

  articleSenior author
  PublisherDOI

• Risk of obesity, diabetes, hypertension, and major adverse cardiovascular events after a switch to an integrase inhibitor: a target trial emulation in REPRIEVE

  The Lancet HIV · 2026-03-28

  articleOpen access
  PublisherOA PDFDOI

• Pitavastatin effects on lipids in relation to major adverse cardiovascular events: a REPRIEVE secondary analysis

  The Lancet HIV · 2026-04-03 · 1 citations

  articleOpen accessSenior author

  BACKGROUND: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) found a 36% reduction in major adverse cardiovascular events (MACE) with pitavastatin in people with HIV. Little is known about the relationship between lipid lowering and MACE in this population. We evaluated pitavastatin effects on lipids and examined mediation of pitavastatin effects on MACE through lipid lowering. METHODS: REPRIEVE was a randomised, double-blind, placebo-controlled phase 3 trial evaluating pitavastatin (4 mg daily) or placebo for prevention of MACE in people with HIV. Participants aged 40-75 years, on stable combination antiretroviral therapy (ART), and at low-to-moderate atherosclerotic cardiovascular disease risk with minimally elevated LDL were followed up for a median of 5·6 years. Centrally tested fasting lipids were captured at entry and annually thereafter. The primary MACE outcome, reported previously, was time to first MACE. Here, we report secondary outcomes on fasting lipids. Linear mixed-effects models were used for assessment of the pitavastatin effect on lipids, Cox regression for relationship of lipids to MACE, and Vansteelandt method for mediation analysis. FINDINGS: REPRIEVE enrolled 7769 participants from March 26, 2015, to July 31, 2019, in 12 countries across five Global Burden of Diseases super-regions. The median baseline LDL was 108 mg/dL, and similar across treatment groups. Pitavastatin effects were primarily observed on LDL, with a modest reduction in triglycerides and no apparent effect on HDL. Based on the longitudinal data modelling, the estimated treatment group difference in LDL at month 12 (pitavastatin minus placebo) was -30 mg/dL (95% CI -31 to -29), corresponding to a 30% reduction. The estimated risk of LDL of ≥100 mg/dL at month 12 was 0·18 in the pitavastatin group and 0·57 in the placebo group (relative risk 0·32, 95% CI 0·30-0·34). A 30% lower time-updated average LDL was associated with 20% lower risk of primary MACE (hazard ratio 0·80, 95% CI 0·68-0·94). Of the pitavastatin effect on MACE, 68% was estimated to be mediated through LDL, although with low precision (95% CI 15-574). INTERPRETATION: LDL is strongly related to MACE, and LDL lowering should be an important goal of primary cardiovascular prevention in people with HIV, even in those with minimally elevated LDL. Treatment should aim to achieve accepted primary care prevention targets for LDL. FUNDING: US National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare.

  PublisherOA PDFDOI

• No evidence of pitavastatin effect on muscle area or density among people with HIV

  AIDS · 2025-07-21 · 2 citations

  articleOpen access

  BACKGROUND: Skeletal muscle area and muscle density are key determinants of physical function and typically decline with increasing age. Statins have well known musculoskeletal effects but whether statins impact muscle area or muscle density is not well established, especially in the setting of randomized treatment. METHODS: REPRIEVE is a double-blind randomized trial evaluating the effect of pitavastatin for primary prevention of major adverse cardiovascular events in people with HIV (PWH). Thoracic paraspinal, pectoralis, and infraspinatus muscle area and muscle density were assessed among Mechanistic Substudy participants with CT at baseline and month 24. RESULTS: Of 804 substudy participants, 510 remained on study treatment and had imaging at baseline and month 24. Median age was 51 years; 17% were natal female, 35% Black, and 27% Hispanic. There were no apparent changes in muscle measures from baseline to month 24 within the treatment groups. The estimated treatment group differences in baseline-adjusted month 24 outcomes were minimal [within 0.5 cm 2 /m for height-adjusted MA with 95% confidence interval (95% CI) bounds within <1 cm 2 /m, and within 1 Hounsfield units (HU) for MD with 95% CI bounds within <3 HU; all P > 0.2]. Findings were generally consistent in subgroup analyses. CONCLUSION: Pitavastatin was associated with no apparent change in muscle measures over 24 months, and with no evidence of detrimental effect among PWH.

  PublisherOA PDFDOI

• Baseline ECG and Cardiovascular Outcomes in People With HIV: Insights From REPRIEVE

  Journal of the American Heart Association · 2025-12-11

  articleOpen access

  BACKGROUND: With antiretroviral therapy, people with HIV (PWH) have an increased burden of cardiovascular disease. The REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) trial demonstrated that pitavastatin reduces major adverse cardiovascular events (MACEs) among PWH at low to moderate traditional atherosclerotic risk. Electrocardiographic abnormalities are common in PWH, but little is known about their association with MACEs. We sought to examine whether baseline electrocardiographic abnormalities are associated with increased MACE risk among a global primary cardiovascular disease prevention cohort of PWH in REPRIEVE. METHODS: In this observational analysis, entry electrocardiographic abnormalities were adjudicated and classified as major or minor abnormalities. Multivariable cause-specific Cox proportional hazards models assessed the association of electrocardiographic abnormalities with MACEs while stratifying for treatment effect. The model improvement with the addition of the ECG to a model with the pooled cohort equations risk score was examined. RESULTS: Among 7719 participants (median age, 50 years; 69% men), 49% had ≥1 electrocardiographic abnormality, with 3% classified as major. Over a median of 5.6 years, a major electrocardiographic abnormality was associated with a 2.42-fold (95% CI, 1.49-3.91) higher hazard of incident MACEs, whereas minor abnormalities were not. Specific abnormalities associated with MACEs were chamber enlargement and infarct/ischemia pattern. No significant subgroup- or treatment-related interaction was observed. Adding electrocardiographic findings to traditional risk factors increased the C-statistic modestly (+0.01). CONCLUSIONS: Among PWH in REPRIEVE, electrocardiographic abnormalities were common, but major electrocardiographic abnormalities were rare. Though major abnormalities were associated with increased hazard of MACEs, routine electrocardiographic screening is unlikely to improve the prediction of future cardiovascular events in this primary prevention population with low to moderate cardiovascular risk.

  PublisherDOI

• Health-related quality of life among people with HIV at low-to-moderate risk for atherosclerotic cardiovascular disease in the REPRIEVE Trial

  AIDS · 2025-11-11

  articleOpen accessSenior authorCorresponding

  BACKGROUND: There is limited evidence concerning the relationship between cardiometabolic characteristics and health-related quality of life (HRQoL), and potential effects of statin therapy among people with HIV (PWH). METHODS: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) enrolled PWH aged 40-75 years on antiretroviral therapy (ART) with low-to-moderate ASCVD risk. Coronary computed tomography angiography assessed coronary plaque among a subset of participants in the REPRIEVE Mechanistic Substudy at baseline and 24 months. The Short Form-36-Item Health Survey Version 2 was collected at baseline, and physical (PCS) and mental (MCS) component summary scores were determined. We explored the relationship of PCS and MCS with cardiometabolic characteristics, coronary atherosclerosis, and assessed change in score by treatment group (pitavastatin vs. placebo). RESULTS: Of 733 participants, median age was 51 years, 84% were male, 34% were Black non-Hispanic, and median years diagnosed with HIV was 15. At baseline, for participants randomized to pitavastatin vs. placebo the median PCS was 54.5 (Q1, Q3: 46.9, 57.7) vs. 54.1 (47.5, 58.0), and the median MCS was 52.9 (44.1, 57.6) vs. 52.8 (44.0, 57.9). In fully adjusted analyses, older age, Black non-Hispanic race/ethnicity, ART regimen class, elevated BMI, and cigarette smoking were associated with lower PCS. No clear trends were apparent with MCS. Between baseline and month 24, declines in PCS and MCS were minimal with no apparent difference by treatment group. CONCLUSIONS: Among this cohort of ART-treated PWH, baseline cardiometabolic risk factors were associated with worse self-reported physical HRQoL, with no apparent effect of statin therapy. TRIAL REGISTRATION: REPRIEVE; NCT02344290; https://clinicaltrials.gov/study/NCT02344290.

  PublisherOA PDFDOI

• Small Effects, Big Impact: Multiple Win Measures Aid Interpretation, But Do Not Forget the Bigger Picture

  Clinical Infectious Diseases · 2025-10-29

  article
  PublisherDOI

• No evidence of a detrimental effect of pitavastatin on neurocognitive function among people with HIV

  AIDS · 2025-06-11 · 5 citations

  articleOpen accessSenior author

  OBJECTIVE: Effects of statins on neurocognitive function remain poorly understood, with some studies suggesting harm and others suggesting benefit. Limited observational data among people with HIV (PWH) is biased by indication for statin prescription. We sought to assess statin effects on neurocognitive function among PWH. DESIGN: We leveraged data from participants co-enrolled in REPRIEVE (randomized trial of pitavastatin vs. placebo among PWH with low-to-moderate cardiovascular risk) and HAILO (observational study involving repeated neurocognitive measures). METHODS: Participants with at least one measure of neurocognitive function before and after REPRIEVE randomization were included. Neurocognitive function was determined by NPZ-4, the average of the Z scores from Hopkins Verbal Learning Test Revised, Trailmaking A and B, and Digit Symbol Test every 48 weeks. Trajectories before and after randomization were analyzed with generalized estimating equation models. RESULTS: Of 181 co-enrolled participants (pitavastatin 88, placebo 93), changes over median 2.3 years on overall and individual neurocognitive scores were small, not meeting a clinically relevant threshold of more than 0.5/year, and similar between arms. Although subgroup analyses were limited by a small sample size, we observed trends toward improved Trailmaking A in participants with baseline impairment who were randomized to pitavastatin vs. placebo and towards worsened NPZ-4 in women randomized to pitavastatin vs. placebo that similarly did not reach threshold for clinical relevance. Other subgroup effects were minimal and not statistically or clinically significant. CONCLUSION: We found no evidence of a detrimental effect of pitavastatin use on a limited battery of neurocognitive assessments among PWH, even among PWH with baseline neurocognitive impairment.

  PublisherOA PDFDOI

• MON-696 Obesity and Metabolic Comorbidities in Young Adults with Perinatal HIV Exposure Without Infection

  Journal of the Endocrine Society · 2025-10-01

  articleOpen access

  Abstract Disclosure: N. Chahal: None. A.K. Arpante: None. J.E. Johnson: None. C.A. Dash: None. M.W. Ockene: None. I. Zheng: None. A. Boutin: None. H. Lee: None. K.E. Corey: None. T.L. Stanley: None. S.K. Grinspoon: None. L.T. Fourman: None. Background: Over 1 million HIV-negative individuals are born to mothers with HIV annually. While mounting evidence indicates an increased risk of metabolic abnormalities among this population in early life, long-term sequelae of perinatal HIV exposure without infection (PHEU) into adulthood remain largely unknown. This study examined the prevalence and prenatal correlates of obesity and metabolic comorbidities in the oldest known cohort of young adults with PHEU versus matched unexposed controls. Methods: In this prospective study, we evaluated 41 young adults with PHEU and 41 controls matched 1:1 on ≥4 of the following factors: age, sex, race/ethnicity, maternal education, maternal substance use disorder, and breastfeeding. Obesity was defined as BMI ≥30 kg/m2 with elevated waist circumference (≥88 cm in females, ≥102 cm in males), or BMI &amp;gt;40 kg/m2. Metabolic comorbidities included impaired glucose tolerance (HbA1c ≥5.7%, fasting glucose ≥100 mg/dL, and/or 2-hour glucose ≥140 mg/dL on oral glucose tolerance test), insulin resistance (HOMA-IR ≥3), hypertension (clinical diagnosis, SBP ≥140 mmHg, and/or DBP ≥90 mmHg), dyslipidemia (total cholesterol ≥200 mg/dL, HDL-C &amp;lt;40 mg/dL, and/or triglycerides ≥150 mg/dL), and hepatic steatosis (controlled attenuation parameter ≥263 dB/m on elastography). A composite metabolic comorbidity score was derived with 1 point assigned to each of the 5 selected outcomes. Framingham 30-year risk of cardiovascular disease (CVD) was calculated. Prenatal history was ascertained via maternal interview and medical records. Results: Young adults with PHEU (24±5 y, 46% male) had higher rates of obesity (51% vs. 29%, P=0.04), impaired glucose tolerance (21% vs. 3%, P=0.01), insulin resistance (24% vs. 2%, P=0.004), hypertension (20% vs. 0%, P=0.003), dyslipidemia (46% vs. 15%, P=0.002), and hepatic steatosis (44% vs. 15%, P=0.006) compared to matched controls. These differences conferred a higher metabolic comorbidity score (1.5±1.4 vs. 0.3±0.7, P&amp;lt;0.001) and 30-year CVD risk (9.7% vs. 5.8%, P=0.02). Relationships of PHEU with BMI, comorbidity score, and CVD risk persisted upon adjusting for young adult (e.g., adverse childhood experiences) and maternal factors (e.g., BMI). PHEU was associated with a higher rate of ≥1 metabolic comorbidity in young adults with (100% vs. 58%, P=0.001) and without obesity (42% vs. 15%, P=0.04). In the PHEU group, lower maternal prenatal CD4 count was associated with higher adult CVD risk (ρ=-0.42, P=0.03). Conclusions: Young adults with PHEU bear a greater burden of obesity and metabolic comorbidities versus unexposed peers. Maternal HIV-related immune dysregulation may contribute to these outcomes. These findings highlight the critical role of the intrauterine environment in shaping adult cardiometabolic disease risk and may have broader implications for other groups including offspring of mothers with obesity. Presentation: Monday, July 14, 2025

  PublisherOA PDFDOI

• Reply

  JACC Advances · 2025-08-08

  letterOpen accessSenior authorCorresponding
  PublisherDOI

Recent grants

• NIH Grant T32HD052961

  NIH · $1.3M · 2017

• NIH Grant K24DK06454508

  NIH · $194k · 2013

• NIH Grant U01AI115711

  NIH · $2.0M · 2019

• NIH Grant F32DK009218

  NIH · $15k

• NIH Grant K24DK064545

  NIH · $1.4M · 2013

Frequent coauthors

• Kathleen V. Fitch

  Massachusetts General Hospital

  302 shared

• Takara L. Stanley

  Harvard University

  246 shared

• Markella V. Zanni

  Harvard University

  228 shared

• Janet Lo

  Harvard University

  185 shared

• Pamela S. Douglas

  Clinical Research Institute

  140 shared

• Michael T. Lu

  Massachusetts General Hospital

  140 shared

• Martin Torriani

  124 shared

• Colleen Hadigan

  National Institutes of Health

  124 shared

Education

• M.D.

  Harvard Medical School

• B.A.

  Harvard College

Awards & honors

• American Society for Clinical Investigation
• Association of American Physicians
• American Federation of Medical Research Investigator of the…
• Edward H. Ahrens Jr. Award for Patient Oriented Research (20…
• Endocrine Society Laureate Award for Translational Research…