Dyslipidemia in the Setting of HIV Infection and Its Management with Statin Therapy Among a Cohort of HIV-Infected Patients in Washington, DC
Open AccessBackground: HIV-infected individuals have a 1.5- to 2-fold greater risk of cardiovascular disease compared with the general population, which can be attributed to a complex interplay of various factors including a higher prevalence of traditional cardiovascular risk factors such as smoking among HIV-infected populations, chronic inflammation and immune activation related to HIV infection, and metabolic abnormalities induced by antiretroviral drugs. Dyslipidemia is a major cardiovascular disease risk factor that is highly prevalent among HIV-infected populations and represents a key potential therapeutic target to reduce cardiovascular disease risk in HIV-infected persons.Study Design: For each analysis, we used demographic, clinical, and laboratory data collected between 2011-2016 for HIV-infected patients aged ≥21 years enrolled in the DC Cohort study, a large multicenter prospective observational study of HIV-infected persons in care in Washington, DC.Analysis 1: Objectives: Immunosuppression and HIV viremia have been found to be associated with unfavorable lipid profiles. Prior research has also shown that older HIV-infected persons may have a greater prevalence of metabolic and cardiovascular disease than is expected due to the independent effects of HIV and age alone. To explore reasons for this disproportionate burden, we assessed whether associations of CD4 count and HIV viral load (VL) with non-high-density lipoprotein cholesterol (non-HDL-C) and high-density lipoprotein cholesterol (HDL-C) differed by age. Methods: Using data for participants with ≥1 cholesterol result and contemporaneous CD4 count and HIV VL results, we conducted multivariable linear regression with generalized estimating equations to model non-HDL-C and HDL-C concentrations. Pairwise interaction terms among CD4 count, HIV VL, and age were included and followed by stratified analyses. Results: Associations between CD4 count/VL and non-HDL-C concentrations differed by age. Higher CD4 count was associated with higher non-HDL-C among patients aged <50 years (β=+0.47 mg/dL per 50-cells/µL-increase in CD4 count [95% CI: 0.29, 0.65]), but was associated with lower non-HDL-C among patients aged 60-69 years (β=-0.69 mg/dL [95% CI: -1.04, -0.34]) (CD4-age interaction, p<0.001). Higher log10 VL was associated with lower non-HDL-C among patients aged <50 years (β=-1.26 mg/dL per log10-increase in VL [95% CI: -2.44, -0.09]), but was associated with higher non-HDL-C among patients aged ≥70 years (β=+14.37 mg/dL [95% CI: 3.54, 25.20]) (VL-age interaction, p<0.001). Although no age differences were detected for HDL-C, higher log10 VL was more strongly associated with lower HDL-C concentration when CD4 count was <200 cells/µL (β=-2.66 mg/dL per log10-increase in VL [95% CI: -3.52, -1.80]) versus 200-500 (β=-2.15 [95% CI: -2.79, -1.52]) or >500 cells/µL (β=-1.51 [95% CI: -2.17, -0.85]) (CD4-VL interaction, p=0.001). Conclusions: We detected a novel age-modified relationship between immunosuppression and viremia and atherogenic cholesterol patterns. These findings may contribute to our understanding of the high risk of dyslipidemia observed among persons aging with HIV.Analysis 2: Objectives: Statins, a class of prescription drugs widely used for the treatment of dyslipidemia and prevention of cardiovascular disease in the general population, are increasingly being prescribed to HIV-infected persons. Using observational cohort data, we quantified the effectiveness of being newly prescribed statin therapy for reducing atherogenic cholesterol concentrations among HIV-infected persons, and compared effect estimates obtained using propensity score matching and traditional regression adjustment, both alone and in combination, as methods to control for confounding factors. Methods: Using a quasi-experimental study design, we compared changes in non-HDL-C and low-density lipoprotein cholesterol (LDL-C) after 6-12 months between patients newly prescribed statin therapy and patients not prescribed statin therapy. Propensity score matching and/or multivariable linear regression with generalized linear mixed models were used. Results: The crude unadjusted mean difference in change in non-HDL-C after 6-12 months between patients prescribed statins and patients not prescribed statins was -32.9 mg/dL (95% CI: -40.3, -25.5). After propensity score matching, the mean difference in change in non-HDL-C between subsets of matched patients with and without statin prescriptions was -10.5 mg/dL (95% CI: -21.5, 0.4), and -10.6 mg/dL (95% CI: -20.4, -0.7) after additional regression adjustment. Using regression adjustment only, the mean difference in change in non-HDL-C was -15.1 mg/dL (95% CI: -20.5, -9.6). Conclusions: Prescribing statin therapy was generally an effective intervention for lowering concentrations of atherogenic cholesterol among HIV-infected persons. In this observational effectiveness study, controlling for confounding factors using both propensity score matching and traditional regression adjustment analytic approaches led to a more complete understanding of the association of interest and added robustness to results.Analysis 3: Objectives: Statin coverage has been examined among HIV-infected patients using 2004 Adult Treatment Panel III (ATP III) and 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, though not with the newer 2014 National Lipid Association (NLA) guidelines. We investigated statin eligibility, prescribing practices, and therapeutic responses using these three guidelines. Methods: We applied ATP III, ACC/AHA, and NLA guidelines to data for participants receiving primary care at their HIV clinic site with ≥1 cholesterol result available. Demographic, behavioral, and clinical predictors of being prescribed statins and of achieving NLA non-HDL-C goals were assessed using multivariable Cox proportional hazards regression. Results: Fifty-two percent of HIV-infected patients were eligible for statins based on ≥1 guideline, including 45% (NLA), 40% (ACC/AHA), and 30% (ATP III). Using each guideline, 49% (NLA), 56% (ACC/AHA), and 73% (ATP III) of eligible patients were prescribed statins. Predictors of new prescriptions included older age (aHR=1.16 [95% CI: 1.08-1.26]/5 years), body mass index ≥30 (aHR=1.50 [95% CI: 1.07-2.11]), and diabetes (aHR=1.35 [95% CI: 1.03-1.79]). Hepatitis C coinfection was inversely associated with statin prescriptions (aHR=0.67 [95% CI: 0.45-1.00]). Among patients with available cholesterol results pre-/post-prescription, 53% achieved their NLA cholesterol goal after six months. Hepatitis C coinfection was positively associated (aHR=1.87 [95% CI: 1.06-3.32]), and depression (aHR=0.56 [95% CI: 0.35-0.92]) and protease inhibitor use (aHR=0.61 [95% CI: 0.40-0.93]) were inversely associated, with NLA goal achievement. Conclusions: Approximately half of HIV-infected patients were eligible for statin therapy based on current United States guidelines, with the highest proportion eligible based on NLA guidelines, yet substantially fewer received prescriptions and achieved treatment goals. Greater compliance with recommended statin prescribing practices may reduce cardiovascular disease risk among HIV-infected individuals.
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