62 Cardiovascular Outcomes in HIV Infection Jens D Lundgren*1, C Sabin2, R Weber3, A D'Arminio Monforte4, W El-Sadr5, P Reiss6, M Law7, F Dabis9, C Pradier10, S deWit11, I Weller2, A Phillips2, N Friis-Moller1, and on behalf of the D:A:D study group 1Copenhagen HIV Prgm, Denmark; 2Royal Free Ctr for HIV Med, Royal Free and Univ Coll Med Sch, London, UK; 3Zurich Univ Hosp, Switzerland; 4L Sacco Hosp, Univ of Milan, Italy; 5Harlem Hosp, Columbia Univ, New York, NY, USA; 6HIV Monitoring Fndn, Amsterdam, The Netherlands; 7Natl Ctr in HIV Epidemiology and Clin Res, Univ of New South Wales, Sydney, Australia; 9Bordeaux Univ Hosp, INSERM U593, France; 10Ctr Hosp Univ Nice, Hosp de l'Archet, France; and 11Ctr Hosp Univ St Pierre, Brussels, Belgium

Backgound: Combination antiretroviral therapy (cART) may increase lipids, impair glucose metabolism and alter body fat distribution. There are no data from randomised trials to confirm whether cART leads to increased risk of cardiovascular disease (CVD).

Aims: To discuss data from observational studies of HIV-infected individuals that have assessed the rate of change in arterial intima-media-thickness (rIMT; marker of atherosclerosis) or CVD, and to discuss potential biological mechanisms that could explain any such associations.

Results: The rIMT in HIV-infected persons is associated with conventional risk factors for atherosclerosis but may be higher than in uninfected controls, whereas it is unclear whether cART directly influences the rIMT. Conversely, most studies suggest an association between CVD risk and exposure to cART, and discrepancies are most likely explained by differences in study design or ascertainment of events. The largest prospective study with centrally validated CVD events – D:A:D - has consistently reported an association between increasing exposure to cART and a higher incidence of myocardial infarction (MI). Several other traditional modifiable (smoking, diabetes mellitus, dyslipidemia, hypertension) and non-modifiable (age, gender, history of CVD, family history of CVD, calendar year of follow-up) risk factors were confirmed in this study. Importantly, after adjustment for these risk factors, the association between exposure to cART and MI risk remained, although was diminished after adjustment for lipids. The association between exposure to cART and MI risk was apparent for all age groups and sexes. Neither clinician-determined lipodystrophy nor immunodeficiency were risk factors.

Conclusions: Whilst exposure to cART adversely affects the risk of CVD, the composite of known CVD risk factors and exposure to cART accounts for the overall CVD-risk in HIV. The mechanisms by which cART induces an increased risk may, in part, be mediated via lipid changes. To date, no other biological effect(s) of cART has been consistently demonstrated to affect the risk of CVD. A possible direct role of specific drug classes remains to be clarified. Hence, individual lipid responses to cART provide partial information as to whether this person’s CVD-risk has been adversely affected by cART. A beneficial role of lipid-lowering agents has not yet been demonstrated.