Introduction: "The continuous advancements and remarkable success of Highly Active Antiretroviral Therapy (HAART) have made long-term survival for HIV patients a reality. However, the persistent presence of the HIV virus, chronic inflammation associated with the virus, and the lifelong impact of medication have led to chronic complications, such as metabolic diseases, becoming significant factors affecting the clinical outcomes of patients undergoing long-term treatment. These issues have become crucial in the treatment and management of patients. One of the key focuses of the 25th International AIDS Conference (AIDS2024) was the ongoing attention to non-AIDS-related complications, which brought new insights into their treatment and management."—Dr. Wei Cao Peking Union Medical College Hospital
Study 1: Subgroup Analysis of the REPRIEVE Study Indicates Increased Cardiovascular Risk Associated with Abacavir Use
This study aimed to explore the common cardiovascular disease (CVD) risks among HIV patients and assess the impact of different antiretroviral therapy (ART) medications on the incidence of major adverse cardiovascular events (MACE). The REPRIEVE study is a multicenter, randomized controlled trial that enrolled HIV patients aged 40-75 who had been on ART for at least 180 days with a CD4 cell count greater than 100 cells/mm³.
Research Methodology
The study collected data from 7,769 participants, including their ART history, baseline risk factors, and cardiovascular health status. Researchers used the Cox proportional hazards model to statistically analyze the first occurrence of MACE (including myocardial infarction, transient ischemic attack/stroke, revascularization, and cardiovascular death), considering differences between treatment groups. The study specifically focused on the use of abacavir (ABC) and its impact on MACE incidence.
Research Results
Among the participants, 31.1% were women, 65.2% were non-White, and the average age was 50 years. The study found that 22% of participants had a history of ABC exposure, and 13% were using ABC at the start of the study. Adjusted analysis using the Cox proportional hazards model showed a significant association between ABC use and increased MACE risk (Figure 1). In contrast, other ART drugs like tenofovir (TDF), thymidine analogs (AZT/d4T), and protease inhibitors (PIs) did not significantly increase MACE risk.
Research Conclusion
This analysis of the latest data from the REPRIEVE study reveals the potential cardiovascular risks associated with ABC use among HIV patients. This finding is crucial for guiding ART treatment choices for HIV patients.
Expert Commentary
This study is a re-analysis of data from the global multicenter REPRIEVE study, which explored the clinical benefits of primary prevention with pitavastatin in HIV patients at low to moderate cardiovascular risk. The primary results, first presented at the 2023 IAS Conference, were groundbreaking and considered practice-changing. Over the past year, researchers have provided more subgroup data from REPRIEVE to address clinical concerns. A subgroup analysis published in JAMA Cardiology in April showed that pitavastatin significantly reduced non-calcified plaque volume, lowered biomarkers related to lipid oxidation and vascular damage, and reduced cardiovascular event rates. The results presented at this conference (OAB3406LB) examined the impact of different antiretroviral drugs on cardiovascular outcomes in the REPRIEVE study population. The findings indicated that both past and current use of ABC significantly increased the risk of major cardiovascular events compared to other antiretroviral drugs. Previously, ABC was shown to affect platelet aggregation and was not recommended for patients with known high cardiovascular risk. This study’s findings will lead us to reassess the cardiovascular risks of long-term ABC use in the general HIV population. The REPRIEVE study population included over a thousand Asian patients, primarily from India and Thailand, providing some regional representation. However, conclusions based on local data in China would be more helpful in formulating and adjusting specific treatment strategies.
Study 2: Cardiovascular Disease Biomarkers in Long-Term Survivors of HIV
With the widespread use of antiretroviral therapy (ART) and the passage of time, the young adult perinatally infected with HIV (YA-PHIV) population is gradually entering a high-risk period for cardiovascular diseases. Inflammatory biomarkers such as high-sensitivity C-reactive protein (hs-CRP), interleukin-18 (IL-18), and soluble CD163 (sCD163) have been associated with increased incidence and mortality from cardiovascular disease. This study aimed to assess the levels of cardiovascular disease biomarkers in YA-PHIV patients receiving pediatric ART at five medical centers in Thailand and explore their relationship with HIV viral load and metabolic syndrome.
Study Design
The study recruited 347 YA-PHIV patients aged 18-25 who were receiving pediatric ART at five medical centers in Thailand. The cohort study design included clinical evaluations and blood sample collection to assess hs-CRP, IL-18, and sCD163 levels. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria.
Research Methodology
After recruitment, patients underwent clinical evaluations and blood sample collection to measure hs-CRP, IL-18, and sCD163 levels. Metabolic syndrome was defined according to NCEP ATP III criteria. hs-CRP levels between 1.0 to <3.0 mg/L were classified as moderate cardiovascular risk, and ≥3 mg/L was classified as high risk. Mood’s median non-parametric test was used to evaluate the association between biomarkers, HIV viral load, and metabolic syndrome.
Research Results
Among the 347 YA-PHIV patients, 54% were biologically female. The median age at enrollment was 21.8 years (IQR 20.1-23.5 years), with a median ART duration of 16.7 years (IQR 13.4-18.4 years). The median CD4 count was 564 cells/mm³ (IQR 356-753), with 14% of patients having a CD4 count <200 cells/mm³, 19% having HIV RNA >1000 copies/mL, and 7.8% having metabolic syndrome.
The study found that 25% of patients had hs-CRP levels indicating moderate cardiovascular risk, and 26% had high-risk levels. Patients with HIV RNA >1000 copies/mL had significantly higher levels of hs-CRP (P=0.001), IL-18 (P<0.001), and sCD163 (P=0.003) compared to those with HIV RNA <1000 copies/mL. Patients with metabolic syndrome were more likely to have elevated hs-CRP (P=0.008) and sCD163 (P=0.07) levels, but no significant difference in IL-18 levels was observed. Additionally, the median IL-18 level was higher in male patients than in female patients.
Research Conclusion
This study suggests that YA-PHIV patients with HIV RNA >1000 copies/mL have elevated cardiovascular disease biomarker levels, while those with metabolic syndrome show significant increases in hs-CRP and sCD163 levels. These findings highlight the importance of HIV viral control and metabolic health status in cardiovascular disease risk among YA-PHIV patients. Further research is needed to determine the predictive value of these biomarkers for cardiovascular events in YA-PHIV patients to develop more effective prevention and treatment strategies.
Expert Commentary
This study focused on the risk and risk factors for metabolic syndrome in the young population perinatally infected with HIV. This group represents a unique cohort of HIV-infected individuals who have been a subject of ongoing concern due to the onset of metabolic and cardiovascular-related diseases. The study included 347 perinatally HIV-infected individuals with a median age of 21.8 years, who had been on antiretroviral therapy for an average of 16.7 years, with a metabolic syndrome prevalence of 7.8%. The study demonstrated a significant association between poor viral control, elevated metabolic-related inflammatory markers, and the onset of metabolic syndrome in this population.
The follow-up study of this unique population illustrates that the persistence of viremia and the ongoing accumulation of immune inflammation are critical factors for the development of metabolic-related events in HIV patients. Immune inflammation accelerates immune aging. In addition to strict viral replication control, identifying potential metabolic-related biomarkers will be crucial for early intervention and the identification of high-risk HIV populations.
Study 3: Low Achievement Rates in Metabolic and Cardiovascular Health Targets Among Women Living with HIV, Urgent Action Needed
The cardiovascular and metabolic health of people living with HIV (PLWH) is receiving increasing attention, particularly among women living with HIV (WWH). To evaluate the achievement rates of major preventive targets such as hypertension, dyslipidemia, and diabetes (H/Dy/DT) among HIV-infected women, this study conducted a cross-sectional analysis to explore the current challenges and urgent actions needed.
Study Design
This cross-sectional study included all HIV-infected women at a clinic, excluding those with a history of myocardial infarction. The study evaluated the achievement rates of H/Dy/DT targets among these patients, as well as differences between Italian and immigrant women based on the European AIDS Clinical Society (EACS) guidelines and individual cardiovascular risk (CVR) scores (using the European Society of Cardiology calculator).
Research Methodology
The research team collected clinical data on the patients, including age, CD4+ cell count, and HIV RNA load, and assessed the patients’ control of hypertension, dyslipidemia, and diabetes. A logistic regression model was used to compare the differences in achieving H/Dy/DT targets between Italian and immigrant women.
Research Results
A total of 292 HIV-infected women were included, with 55.5% being Italian and 44.5% being immigrant women. The median age was 50 years (IQR: 42-58 years), and the median CD4+ cell count was 617.5 cells/mm³ (IQR: 448-825). The vast majority of patients (94.5%) had HIV RNA levels below 50 copies/mL, with a median HIV infection duration of 16 years (IQR: 9-25.8).
The study found that only 76% of the patients achieved a low cardiovascular risk score, 19% were at high risk, and 5% were at extremely high risk. Among Italian women, 28.4% and 6.2% were at high and extremely high risk, respectively, while these proportions were 7.7% and 3.8% among immigrant women (Figure 2). Although immigrant women had better glycemic control (P=0.032), the overall achievement rates for hypertension and lipid control were low, particularly among patients with high CVR.
Research Conclusion
This study reveals that even with cardiovascular screening, the achievement rates for metabolic and cardiovascular health targets among HIV-infected women are suboptimal, especially among immigrant women. The study calls for more aggressive pharmacological interventions, patient adherence assessments, and the promotion of healthy lifestyles. Additionally, redesigning existing healthcare models to better meet the comprehensive health needs of HIV-infected women has become an urgent priority.
This finding sounds an alarm for the health management of HIV-infected women, emphasizing the importance of strengthening interventions for cardiovascular and metabolic health in future research and clinical practice.
Expert Commentary
While the first two studies have enhanced our understanding of non-AIDS-related complications, this study highlights the gap between ideal and actual achievement in metabolic-related targets. The study, conducted in Italy, reflects the global situation in the treatment and management of metabolic-related complications among HIV patients. It indicates that proactive interventions and target achievement for critical metabolic indicators such as blood pressure, lipids, and blood glucose are far from sufficient among the broader HIV-infected population. In this study, the target achievement rates for lipid and blood pressure control were 5% and 25%, respectively, compared to ideal treatment goals.
Knowing is easy; doing is hard, especially for the HIV population that is just beginning to manage metabolic complications. Whether from a doctor’s awareness, patient education, or practical actions in doctor-patient collaborative management, the treatment intervention and standard management of metabolic complications still have a long way to go.
