Introductory talk D Costagliola
Chapter 1 The current debate on abacavir
All or majority of patients antiretroviral-experienced at ABC initiation All or majority of patients antiretroviral naive at ABC inclusion Summary of studies on the association between exposure to abacavir the risk of myocardial infarction 1. Lundgren JD, et al. CROI 2009. Abstract 44LB.2. Lang S, et al. CROI 2009. Abstract 43LB.3. SMART. AIDS. 2008;22:F17-F24.4. Carr A, et al. CROI 2009. Abstract 576.5. Cutrell A, et al. IAC 2008. Abstract WEAB0106.6. Benson C, et al. CROI 2009. Abstract 721. 7. McComsey G, et al. 16th CROI 2009. Abstract 732. Can we extrapolate the results to naive patients?
Exposure to abacavir and other NRTIsand risk of MI, FHDH Study This is different from D:A:D Without D:A:D, we would have found no association Adjusted for hypertension, smoking, family history of premature CAD, use of cocaine and/or IV drug use, plasma HIV-1 RNA level, CD4/CD8 cells ratio, exposure to emtricitabine, atazanavir, ritonavir and tipranavir
Exposure to abacavir and other NRTIsand risk of MI, FHDH Study The impact of cardiovascular risk factors on the likelihood of receiving tenofovir and abacavir is big Adjusted for hypertension, smoking, family history of premature CAD, use of cocaine and/or IV drug use, plasma HIV-1 RNA level, CD4/CD8 cells ratio, exposure to emtricitabine, atazanavir, ritonavir and tipranavir
Exposure to NNRTIs and PIs and risk of MI, FHDH study No such impact for NNRTIs and PIs Adjusted for hypertension, smoking, family history of premature CAD, use of cocaine and/or IV drug use, plasma HIV-1 RNA level, CD4/CD8 cells ratio, exposure to emtricitabine, atazanavir, ritonavir and tipranavir
Conclusion • Can the results be extrapolated to naive patients? • Without DAD, we would have found nothing • In France, the confounders played a higher role on the prescription of NRTIs, in particular tenofovir and abacavir, than on the prescription of NNRTIs or of PIs • If true also in other countries, the results of the different studies will be more likely to be concordant for NNRTIs and for PIs and discordant for NRTIs • Results of observational studies will be more robust for NNRTIs and PIs than for NRTIs
Chapter 2 Risks and relationship between HIV viremia and myocardial infarction
Observed and predicted rates of myocardial infarction by duration of CART 8 7 Observed rates 6 5 Rates per thousand person years Best estimate of predicted rates 4 3 2 1 0 None < 1 year 1-2 years 2-3 years 3-4 years 4+ years Duration of CART Law et al, HIV Med 2006
HIV RNA and risk of serious non-AIDS events: Smart CROI 2008 – A, Phillips (plenary presentation) All serious non-AIDS Non-AIDS malignancy Renal CVD Liver Other non-AIDS death 0,2 0,5 1,0 1,5 Adjusted hazard ratio < 400 vs, > 400 copies/mL Adjusted for age, gender, prior AIDS, hep B/C, smoking, latest CD4 count SMART, unpublished
Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy. Marin et al. AIDS (in press) HIV RNA level and risk of death from cardiovascular disease (n=36) Variables Adj* Hazards Ratio 95% CI p-value Latest CD4 cell count (/µl) 0.14 349-200 vs. ≥350 1.15 (0.51-2.63) 199-50 vs. ≥350 0.89 (0.28-2.82) <50 vs. ≥350 4.15 (1.14-15.17) Latest HIV RNA (log10/ml) ≥5 vs. <5 3.86 (1.57-9.51) 0.003 *Adjusted for age, sex, exposure category, Hepatitis C serostatus, first line cART The risk of death from a cardiovascular cause was associated with HIV RNA level
Risk factors of MI in HIV infected patients apart from treatment FHDH ANRS CO4 *man more than 50 years or woman more than 60 years, current smoker or smoking cessation < 3years, family history of premature coronary arterial disease, hypertension, hypercholesterolemia, diabetes and cocaine and/or intravenous drug use
Conclusion • The traditional cardiovascular risk factors, including cocaine and IV drug use, are very strong risk factors of MI in HIV-1 infected patients • The role of HIV parameters must also be accounted for • Plasma HIV-1 RNA (positive impact of cART) • CD4/CD8 ratio • Activation? • Inflammation? • No role of CD4 cell count?