Register      Login
Sexual Health Sexual Health Society
Publishing on sexual health from the widest perspective
RESEARCH ARTICLE

Macrolide use and the risk of vascular disease in HIV-infected men in the Multicenter AIDS Cohort Study

Ian J. Woolley A E , Xiuhong Li B , Lisa P. Jacobson B , Frank J. Palella C and Lars Ostergaard D
+ Author Affiliations
- Author Affiliations

A Infectious Diseases Department, Alfred Hospital, Monash University Medical School, Prahran 3004, Victoria, Australia.

B Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.

C Northwestern University, Feinberg School of Medicine, Division of Infectious Diseases, Chicago, Illinois 60611, USA.

D Research Unit Q, Department of Infectious Diseases, Skejby Sygehus, Aarhus University Hospital, 8200 Aarhus N, Denmark.

E Corresponding author. Email: Ian.Woolley@med.monash.edu.au

Sexual Health 4(2) 111-119 https://doi.org/10.1071/SH06052
Submitted: 8 September 2006  Accepted: 26 March 2007   Published: 23 May 2007

Abstract

Background: There has been increasing concern that HIV-infected individuals may be more at risk for cardiovascular events in the highly-active antiretroviral therapy (HAART) era. This study examined the risk of thromboembolic events in HIV-infected and non-infected individuals and the effect of macrolide prophylaxis on those outcomes. Methods: A subcohort analysis was undertaken using data collected in the Multicenter AIDS Cohort Study to examine the relative risk of vascular events (myocardial infarction, unstable angina and ischaemic stroke). Cox proportional hazard model using age as the time scale with time varying cofactors obtained at each semi-annual visit were used to assess the independent effect of macrolide use. Results: Controlling for other significant effects including race and smoking, HIV-infection was not independently associated with vascular events. Increased risk was observed among those who used HAART (relative hazard 1.09, 95% confidence intervals 1.00–1.19 in multivariate model), antihypertensive treatment (1.81 [1.26–2.60]), lipid-lowering medication (1.65 [1.12–2.42]), and antibiotics (1.72 [1.25–2.36]). The protective association of macrolide use for a vascular event in the HAART era was also significant (0.10 [0.01–0.75]). Conclusions: Traditional risk factors are important in the pathogenesis of vascular events in HIV-infected individuals. Macrolide antibiotics may have a protective effect in the HIV-infected individuals in the HAART era.

Additional keywords: HIV, macrolide, myocardial infarct, vascular event.


Acknowledgements

Data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS) with centres (Principal Investigators) at The Johns Hopkins University Bloomberg School of Public Health (Joseph B. Margolick, Lisa Jacobson), Howard Brown Health Center and North-western University Medical School (John Phair), University of California, Los Angeles (Roger Detels, Beth Jamieson), and University of Pittsburgh (Charles Rinaldo). MACS is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute. UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041. The website is located at http://www.statepi.jhsph.edu/macs/macs.html. Thanks to Søren P. Johnsen and Henrik T. Sorensen for their contributions to this paper.


References


[1] Palella FJ,  Delaney KM,  Moorman AC,  Loveless MO,  Fuhreh J, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338 853–60.
Crossref | GoogleScholarGoogle Scholar | PubMed | [verified 11 April 2007]

[21] Detels R,  Munoz A,  McFarlane G,  Kingsley LA,  Margolick JB,  Giorgi J, et al. Effectiveness of potent antiretroviral therapy on time to AIDS and death in men with known HIV infection duration. Multicenter AIDS Cohort Study Investigators J Am Med Assoc 1998; 280 1497–503.
Crossref | GoogleScholarGoogle Scholar |

[22] Korn EL,  Graubard BI,  Midthune D. Time-to-event analysis of longitudinal follow-up of a survey: choice of the time-scale. Am J Epidemiol 1997; 145 72–80.
PubMed |

[23] Kaplan JE,  Masur H,  Holmes KK,  McNeil MM,  Schonberger LB,  Navin TR, et al. USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: introduction. USPHS/IDSA Prevention of Opportunistic Infections Working Group. Clin Infect Dis 1995; 21 S1–11.
PubMed |

[24] Miserez AR,  Muller PY,  Barella L,  Schwietert M,  Erb P,  Vernazza PL, et al. A single-nucleotide polymorphism in the sterol-regulatory element-binding protein 1c gene is predictive of HIV-related hyperlipoproteinaemia. Swiss HIV Cohort Study. AIDS 2001; 15 2045–9.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[25] Manuel O,  Thiebaut R,  Darioli R,  Tarr PE. Treatment of dyslipidaemia in HIV-infected persons. Expert Opin Pharmacother 2005; 6 1619–45.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[26] Visnegarwala F,  Maldonado M,  Sajja P,  Minihan JL,  Rodriguez-Barradas MC,  Ong O, et al. Lipid lowering effects of statins and fibrates in the management of HIV dyslipidemias associated with antiretroviral therapy in HIV clinical practice. J Infect 2004; 49 283–90.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[27] van’t Wout AB,  Swain JV,  Schindler M,  Rao U,  Pathmajeyan MS,  Mullins JI, et al. Nef induces multiple genes involved in cholesterol synthesis and uptake in human immunodeficiency virus type 1-infected T cells. J Virol 2005; 79 10053–8.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[28] Rose H,  Woolley I,  Hoy J,  Dart A,  Bryant B,  Mijch A, et al. HIV infection and high density lipoprotein: the effect of the disease versus the effect of treatment. Metabolism 2006; 55 90–5.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[29] El-Sadr WM,  Mullin CM,  Carr A,  Gibert C,  Rappoport C,  Visnegarwala F, et al. Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naive cohort. HIV Med 2005; 6 114–21.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[30] Riddler SA,  Smit E,  Cole SR,  Li R,  Chmiel JS,  Dobs A, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA 2003; 289 2978–82.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[31] Brown TT,  Cole SR,  Li X,  Kingsley LA,  Palella FJ,  Riddler SA, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the Multicenter AIDS Cohort Study. Arch Intern Med 2005; 165 1179–84.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[32] Holmberg SD,  Moorman AC,  Williamson JM,  Tong TC,  Ward DJ,  Wood KC, et al. HIV Outpatient Study (HOPS) investigators. Protease inhibitors and cardiovascular outcomes in patients with HIV-1. Lancet 2002; 360 1747–8.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[33] Bozzette SA,  Ake CF,  Tam HK,  Chang SW,  Louis TA. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. N Engl J Med 2003; 348 702–10.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[34] Constans J,  Marchand JM,  Conri C,  Peuchant E,  Seigneur M,  Risp P, et al. Asymptomatic atherosclerosis in HIV positive patients: A case-control ultrasound study. Ann Med 1995; 27 683–5.
PubMed |

[35] Etminan M,  Carleton B,  Delaney JA,  Padwal R. Macrolide therapy for Chlamydia pneumoniae in the secondary prevention of coronary artery disease: a meta-analysis of randomized controlled trials. Pharmacotherapy 2004; 24 338–43.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[36] Wells BJ,  Mainous AG,  Dickerson LM. Antibiotics for the secondary prevention of ischemic heart disease: a meta-analysis of randomized controlled trials. Arch Intern Med. 2004; 164 2156–61.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[37] Lim LL,  Kotsanas D,  Ostergaard L,  Woolley I. The use of antibiotics as secondary prevention for cardiac events. Pharmacotherapy 2004; 24 1652–3.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[38] Tositti G,  Rassu M,  Fabris P,  Giordani M,  Cazzavillan S,  Reatto P, et al. Chlamydia pneumoniae infection in HIV-positive patients: prevalence and relationship with lipid profile. HIV Med 2005; 6 27–32.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[39] Woolley IJ,  Larsen M,  Jones S,  Gahan ME,  Jasenko I,  Johnsen SP, et al. Ostergaard Chlamydia pneumoniae in HIV-infected patients and controls assessed by a novel whole blood interferon-gamma assay, serology and PCR. Clin Microbiol Infect 2004; 10 820–5.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[40] Ridker PM,  Stampfer MJ,  Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA 2001; 285 2481–5.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[41] Li JJ,  Fang CH. C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular diseases. Med Hypotheses 2004; 62 499–506.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[42] del Rincon ID,  Williams K,  Stern MP,  Freeman GL,  Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 2001; 44 2737–45.
Crossref | GoogleScholarGoogle Scholar | PubMed |

[43] Amsden GW. Anti-inflammatory effects of macrolides–an underappreciated benefit in the treatment of community-acquired respiratory tract infections and chronic inflammatory pulmonary conditions? J Antimicrob Chemother 2005; 55 10–21.
Crossref | GoogleScholarGoogle Scholar | PubMed |