HIV-infected individuals face a markedly increased risk of cardiovascular disease (CVD), even when viremia is suppressed by combined antiretroviral therapy (cART). Mechanisms underlying HIV-associated CVD risk are incompletely understood and specific guidelines on cardioprotective care for this population are not available. Characterizing and reducing CVD risk among HIV-infected women represents a particular challenge. HIV-infected women have a lower prevalence of select traditional CVD risk factors (e.g., hypertension, smoking) and are less likely than HIV-infected men to be offered preventive cardiac care in clinical practice. However, several studies suggest women with HIV are just as likely as their male counterparts to incur an MI. Indeed, a large-scale US epidemiologic study shows that among HIV-infected women, unadjusted rates of MI modestly exceed those among HIV-infected men. Moreover, the same study reveals a significantly higher adjusted relative risk of MI in HIV infected-women versus uninfected females (2.89) as compared with HIV-infected men versus uninfected males (1.4). The proposed study aims to identify sex-specific mechanisms of CVD risk and risk reduction in HIV, addressing an NIH research priority. Importantly, the proposed study leverages the infrastructure of the largest primary prevention trial in the field of HIV-associated CVD: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE, A5332). The REPRIEVE trial, now launching, will test among 6500 HIV-infected persons ages 40-75 with low traditional CVD risk scores whether statin therapy reduces clinical cardiovascular events. Statin therapy has appeal in HIV in that it both reduces LDL cholesterol levels and dampens atherogenic immune activation, which persists in persons with HIV on cART. Work from our group and others suggests immune activation is highest in HIV-infected women (vs. HIV-infected men), particularly among those women who have undergone menopause. Through the proposed project, we will assess whether immune activation contributes uniquely to CVD risk among HIV-infected women across the reproductive aging spectrum and how statins may reduce CVD risk through effects on this pathway. Answers to these questions will influence the development of CVD prediction and prevention strategies tailored to the aging female HIV-infected population worldwide (~17 million). Maximizing our power to elucidate sex-specific CVD mechanisms in HIV, we will also design, implement, and evaluate the effectiveness of an evidence-based education/awareness recruitment campaign to enhance female enrollment in the REPRIEVE trial.
This proposed study will assess whether women with HIV have unique factors which put them at increased risk for heart disease and whether a common class of medicines, statins, affects these factors. The proposed study will be performed as part of the recently launched REPRIEVE trial - a 6500-person study of statin therapy among individuals with HIV. As part of this study, we will also design and test unique strategies to increase recruitment of women to the parent REPRIEVE trial.
|Gogia, Shawnbir; Coromilas, Alexandra; Regan, Susan et al. (2018) Cardiovascular Risk Profile of Transgender Women With HIV: A US Health Care Database Study. J Acquir Immune Defic Syndr 79:e39-e41|
|Looby, Sara E; Psaros, Christina; Raggio, Greer et al. (2018) Association between HIV status and psychological symptoms in perimenopausal women. Menopause 25:648-656|
|Foldyna, Borek; Fourman, Lindsay T; Lu, Michael T et al. (2018) Sex Differences in Subclinical Coronary Atherosclerotic Plaque Among Individuals With HIV on Antiretroviral Therapy. J Acquir Immune Defic Syndr 78:421-428|
|Srinivasa, Suman; Lu, Michael T; Fitch, Kathleen V et al. (2018) Epicardial adipose tissue volume and cardiovascular risk indices among asymptomatic women with and without HIV. Antivir Ther 23:1-9|
|Stone, Lauren; Looby, Sara E; Zanni, Markella V (2017) Cardiovascular disease risk among women living with HIV in North America and Europe. Curr Opin HIV AIDS 12:585-593|
|Zanni, Markella V; Stone, Lauren A; Toribio, Mabel et al. (2017) Proprotein Convertase Subtilisin/Kexin 9 Levels in Relation to Systemic Immune Activation and Subclinical Coronary Plaque in HIV. Open Forum Infect Dis 4:ofx227|
|Zanni, Markella V; Fitch, Kathleen; Rivard, Corinne et al. (2017) Follow YOUR Heart: development of an evidence-based campaign empowering older women with HIV to participate in a large-scale cardiovascular disease prevention trial. HIV Clin Trials 18:83-91|
|Kearns, Alison; Burdo, Tricia H; Qin, Xuebin (2017) Editorial Commentary: Clinical management of cardiovascular disease in HIV-infected patients. Trends Cardiovasc Med 27:564-566|
|Raghavan, Avanthi; Rimmelin, Dodie E; Fitch, Kathleen V et al. (2017) Sex Differences in Select Non-communicable HIV-Associated Comorbidities: Exploring the Role of Systemic Immune Activation/Inflammation. Curr HIV/AIDS Rep 14:220-228|
|Looby, Sara E; Fitch, Kathleen V; Srinivasa, Suman et al. (2016) Reduced ovarian reserve relates to monocyte activation and subclinical coronary atherosclerotic plaque in women with HIV. AIDS 30:383-93|