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Association between CD4 and HIV RNA with non AIDS-related causes of death in the era of combination antiretroviral therapy (cART)
Presented by Benoît Marin, France.
Marin B.1, Thiébaut R.2, Rondeau V.2, Costagliola D.3, Dorrucci M.4, Bucher H.5, Hamouda O.6, Walker S.7, Bhaskaran K.7, Chêne G.1, CASCADE Study Group
1INSERM U593, Bordeaux, France, 2INSERM U875, Bordeaux, France, 3INSERM U720, Paris, France, 4Istituto Superiore di Sanita, Rome, Italy, 5Basel Institute for Clinical Epidemiology, Basel, Switzerland, 6Robert Koch-Institute, Berlin, Germany, 7MRC Clinical Trial Unit, London, United Kingdom
Objectives: To assess the relationship between markers of HIV progression and five specific causes of death in patients followed since 1996.
Methods: We used CASCADE data of 23 European, Australian and Canadian cohorts of adult HIV-seroconverters measuring time from seroconversion to specific cause of death (CoD) or censoring date. Proportional hazards modelling of each specific CoD allowed for delayed entry and competing risks. Potential determinants were nadir CD4 cell count, HIV RNA, AIDS stage C (time-dependent covariates), and age at seroconversion, gender, HIV transmission category, Hepatitis C Virus (HCV) serostatus and type of first line cART.
Results: Among 10,661 seroconverters, 665 deaths were reported during 83,830 persons-year of follow-up: 186 (28%) were AIDS-related, 366 (55%) non AIDS-related (51 non-AIDS infections, 49 liver diseases, 47 non-AIDS malignancies, 40 cardio-vascular diseases) and 113 (17%) of unknown origin. AIDS-related deaths were strongly associated with nadir CD4 count, HIV RNA level and AIDS stage C. Fatal non-AIDS infections were associated with a lower nadir CD4 <50 vs ³350 cells/ml: hazard ratio (HR)=3.7 (CI 1.3-10.5), HIV RNA level ³5 log10copies/ml: HR=5.4 (CI 2.6-11.2) and AIDS stage C: HR=5.0 (CI 2.2-11.6). Fatal liver diseases were associated with nadir CD4 <200 vs ³350 cells/ml: HR=4.6 (CI 1.8-11.7), and HCV co-infection: HR=12.7 (CI 4.2-38.5). Fatal non-AIDS malignancies were associated with nadir CD4 200-349: HR=3.2 (CI 1.4-7.2) and nadir CD4 <200: HR=2.7 (CI 1.1-6.6) vs ³350 cells/ml, AIDS stage C: HR=2.5 (CI 1.2-5.0) and age ³35 years: HR=2.8 (CI 1.5-5.4). Fatal cardiovascular diseases were associated with AIDS stage: HR=6.9 (CI 3.1-15.3) and age ³35 years: HR=4.1 (CI 1.8-9.1).
Conclusions: In cART era, death due to non-AIDS infections, liver diseases, non-AIDS malignancies and cardio-vascular diseases are frequent and associated with either laboratory or clinical markers of HIV progression. Earlier initiation of cART might have an impact on other fatal morbidities than AIDS.
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