Association of Clinical and Therapeutic Factors with Incident Dyslipidemia in a Cohort of Human Immunodeficiency Virus–Infected and Non-Infected Adults: 1994

Abstract

Objective:

The aim of this study was to determine the incidence rate of dyslipidemia in a retrospective cohort of human immunodeficiency virus (HIV)-infected and non-HIV-infected adults and to evaluate the association of incident dyslipidemia with exposure to combination antiretroviral therapy (cART).

Methods:

The study cohort included HIV-infected individuals and a matched group of non-HIV-infected individuals served through the South Carolina Medicaid database in 1994–2011. Linkage with the HIV/AIDS surveillance database provided time-varying viro-immunological status. Time-dependent proportional hazards analysis and marginal structural models were used to assess the demographic, therapeutic, and clinical factors associated with incident dyslipidemia.

Results:

Among 13,632 adults with a median age of 39 years, the overall incidence rate per 1000 person years of dyslipidemia was higher in cART-treated compared to cART-naïve and matched non-HIV groups (24.55 vs. 14.32 vs. 23.23, respectively). Multivariable results suggested a significantly higher risk of dyslipidemia in the cART-treated HIV-infected group [adjusted hazard ratio (aHR)=1.18; 95% confidence interval (CI)=1.07–1.30] and a significantly lower risk in the cART naïve HIV-infected group (aHR=0.66; CI=0.53–0.82) compared to the control non-HIV-infected group. Marginal structural modeling suggested a significant association between incident dyslipidemia and exposure to both protease inhibitor- [adjusted rate ratio (aRR)=1.27; CI=1.08–1.49] and non-nucleoside reverse transcriptase inhibitor- (aRR=1.78; CI=1.19–2.66) based cART regimens. Pre-existing hypertension, obesity, and diabetes increased the risk of dyslipidemia, whereas hepatitis C virus, lower CD4⁺ T cell count, and higher HIV viral load had a protective effect.

Conclusions:

Incident dyslipidemia is lower in the early stages of HIV infection, but may significantly increase with cumulative exposure to cART. Viro-immunological status and underlying comorbidities have a strong association with the onset of dyslipidemia.

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References

Walensky

, Paltiel

, Losina

et al. The survival benefits of AIDS treatment in the United States. J Infect Dis, 2006; 194:11–19.

Palella

Jr. , Delaney

, Moorman

et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med, 1998; 338:853–860.

High

, Effros

, Fletcher

et al. Workshop on HIV Infection and Aging: What is known and future research directions. Clin Infect Dis, 2008; 47:542–553.

Giannarelli

, Klein

, Badimon

. Cardiovascular implications of HIV-induced dyslipidemia. Atherosclerosis, 2011; 219:384–389.

Palella

Jr. , Baker

, Moorman

et al. Mortality in the highly active antiretroviral therapy era: Changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr, 2006; 43:27–34.

Aberg

. Cardiovascular complications in HIV management: Past, present, and future. J Acquir Immune Defic Syndr, 2009; 50:54–64.

, Hsue

. Cardiovascular manifestations of HIV infection. Heart, 2009; 95:1193–1202.

Friis-Moller

, Reiss

, Sabin

et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med, 2007; 356:1723–1735.

Pefura Yone

, Betyoumin

, Kengne

et al. First-line antiretroviral therapy and dyslipidemia in people living with HIV-1 in Cameroon: A cross-sectional study. AIDS Res Ther, 2011; 8:33.

10.

Dube

, Cadden

. Lipid metabolism in treated HIV Infection. Best Pract Res Clin Endocrinol Metab, 2011; 25:429–442.

11.

Crane

, Grunfeld

, Willig

et al. Impact of NRTIs on lipid levels among a large HIV-infected cohort initiating antiretroviral therapy in clinical care. AIDS, 2011; 25:185–195.

12.

Armstrong

, Liu

, Okuma

et al. Dyslipidemia in an HIV-positive antiretroviral treatment-naive population in Dar es Salaam, Tanzania. JAIDS J Acq Immune Defic Syndr, 2011; 57,2:141–145.

13.

Tebas

. HIV and cardiometabolic abnormalities: New perspectives and treatment update. J Acquir Immune Defic Syndr, 2008; 49,Suppl 2:S77–S78.

14.

Green

. Evaluation and management of dyslipidemia in patients with HIV infection. J Gen Intern Med, 2002; 17:797–810.

15.

Anastos

, Lu

, Shi

et al. Association of serum lipid levels with HIV serostatus, specific antiretroviral agents, and treatment regimens. J Acquir Immune Defic Syndr, 2007; 45:34–42.

16.

Goff

, Bertoni

, Kramer

et al.

Dyslipidemia prevalence, treatment, and control in the Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation, 2006; 113:647–656.

17.

Palios

, Kadoglou

, Lampropoulos

. The pathophysiology of HIV-/HAART-related metabolic syndrome leading to cardiovascular disorders: the emerging role of adipokines. Exp Diabetes Res, 2012; 2012:103063.

18.

Samaras

, Wand

, Law

et al. Prevalence of metabolic syndrome in HIV-infected patients receiving highly active antiretroviral therapy using International Diabetes Foundation and Adult Treatment Panel III criteria: associations with insulin resistance, disturbed body fat compartmentalization, elevated C-reactive protein, and [corrected] hypoadiponectinemia. Diabetes Care, 2007; 30:113–119.

19.

Clotet

, van der

Valk M

, Negredo

et al. Impact of nevirapine on lipid metabolism. J Acquir Immune Defic Syndr, 2003; 34,Suppl 1:S79–S84.

20.

Buscher

, Giordano

. Gaps in knowledge in caring for HIV survivors long-term. JAMA21304:340–341.

21.

Coca-Perraillon

. Local and global optimal propensity score matching. Statistics and Data Analysis, 2007. http://www2.sas.com/proceedings/forum2007/185-2007.pdf. 2011 December 3.

22.

Reif

, Geonnotti

, Whetten

. HIV infection and AIDS in the Deep South. Am J Public Health, 2006; 96:970.

23.

Riddler

, Smit

, Cole

et al. Impact of HIV infection and HAART on serum lipids in men. JAMA, 2003; 289:2978–2982.

24.

Shor-Posner

, Basit

, Lu

et al. Hypocholesterolemia is associated with immune dysfunction in early human immunodeficiency virus-1 infection. Am J Med, 1993; 94:515–519.

25.

Enkhmaa

, Anuurad

, Zhang

et al. HIV disease activity as a modulator of lipoprotein(a) and allele-specific apolipoprotein(a) levels. Arterioscler Thromb Vasc Biol, 2013; 33:387–392.

26.

Dubé

, Stein

, Aberg

et al. Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Dis, 2003; 37:613–627.

27.

Dube

. Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medical Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Dis, 2003; 37:613–627.

28.

Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) JAMA, 2001; 285:2486–2497.

29.

Pullinger

, Aouizerat

, Gay

et al. Metabolic abnormalities and coronary heart disease risk in human immunodeficiency virus-infected adults. Metab Syndr Relat Disord, 2010; 8:279–286.

30.

O'Meara

, Kardia

, Armon

, Brown

, Boerwinkle

, Turner

. Ethnic and sex differences in the prevalence, treatment, and control of dyslipidemia among hypertensive adults in the GENOA study. Arch Intern Med, 2004; 164:1313–1318.

31.

Sharma

, Pavlik

. Dyslipidaemia in African Americans, Hispanics and Whites with type 2 diabetes mellitus and hypertension. Diabetes Obes Metab, 2001; 3:41–45.

32.

Stapleton

, Bennett

, Bosch

et al. Effect of antiretroviral therapy and hepatitis C co-infection on changes in lipid levels in HIV-infected patients 48 weeks after initiation of therapy. HIV Clin Trials, 2007; 8:429–436.

33.

Grinspoon

, Carr

. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med, 2005; 352:48–62.

Association of Clinical and Therapeutic Factors with Incident Dyslipidemia in a Cohort of Human Immunodeficiency Virus–Infected and Non-Infected Adults: 1994–2011