1 TOXICIDAD SECUNDARIA AL TRATAMIENTO ANTIRRETROVIRAL Y VIHEugènia Negredo Fundació Lluita contra la Sida Hospital Germans Trias i Pujol Badalona 13 Marzo 2012

2 # Causas de muerte 90 centros en Francia. N= pacientes

3 Cardiovascular Biomarcadores inflamatorios Marcadores subclínicosEventos clínicos

4 Biomarcadores de inflamaciónAbstracts  , Jason Baker #177. James Stein (cardiólogo) The value of biomarker research VIH e inflamación: Tamaño muestral pequeño Observacionales Seguimiento corto “Inconsistent results but promising. Treat the HIV and CVRF.”

5 Asymmetric Dimethylarginine (ADMA)Nuevo marcador de inflamación. Marcador de disfunción arterial. Inhibidor competitivo de oxido nitroso endotelial. Consecuenciasdilatación arterial / aterosclerosis / eventos CV y muerte

6 Asymmetric Dimethylarginine (ADMA)# 831. J Baker # 832. K Kurz # 833. R Parikh, P Shue 48sem ADMA 10,3% (p=0.003) 12sem ADMA (p<0.001) neopterina (p<0.001) VIH+  ADMA vs VIH-  CD4   ADMA  CV VIH   ADMA? VIH  disfunción arterial por  ADMA (producción o eliminación?) ARV  mejora función endotelial mediada por ON a través ADMA

7 Marcadores subclínicosAbstracts:  Ultrasonidos (cIMT)  RM (CAC)  Disfunción endotelial

8 # 122. Microbial translocation and progression of atherosclerosis# 122. Microbial translocation and progression of atherosclerosis. T Kelesidis. Objective: RANKL, LPS, sCD14, dys-HDL progression of CIMT Stored samples from a prospective 3-year study (ACTG 5078) of carotid intima-media thickness (CIMT) Study population: - HIV+ (HIV RNA <500 copies/mL) n=55: - PI, n = 29; - NNRTI, n = 26 - HIV– (n = 36) matched for age, smoking status, and race.

9 Multivariate analysis (HIV+): the yearly rate of change in cIMT- Every 10 mg/mL increase in sCD14  15.2 mm/y (95%CI 0.66 to 29.8, p = 0.04) - Every 100 pg/mL increase in LPS   0.49 mm/y (CI 0.18 to 0.81, p = 0.003). -No significant association with dys-HDL and RANKL levels

10 # 124. Statin and Risk of Serious Non-AIDS-Defining Events (ACTG ALLRT Cohort). Edgar Overton.N= 3601 subjects who initiated ART, not on a statin at ALLRT entry. Primary endpoint: time to first major clinical event (CV event, renal or hepatic disease, incident diabetes, thrombotic or embolic event, non-traumatic fracture, non-AIDS-defining malignancy, serious bacterial infection, or non-accidental death).

11 “Estatinas” “No-estatinas”- Reducción del 18% en el tiempo a primer evento (p=ns). - Reducción del 55% en neoplasias (aHR 0.45 (0.21 to 0.97).

12 # 822. Inmunosupression and CVD (D:A:D)- Cohorts I and II of the D:A:D Study (n=33,301) - Followed from study entry to the earliest of an endpoint, death, 1st February 2010 or 6 months after the last clinic visit. Unadjusted analyseslatest or nadir CD4 counts <350 cells/mm3 tended to experience higher rates of all four endpoints. - Controlling for potential covariates no strong evidence that this higher risk remained. Stroke and CVD rates remain substantially higher in those with a latest CD4 <100 cells/mm3.

13 # 822. Inmunosupression and CVD (D:A:D)

14 # 823. ATV Is Not Associated with an Increased Risk of CV Events (D:A:D). A d’Arminio Monfortepers/año con ATV // pers/año sin ATV

15 Factores predisponentesMETABOLISMO ÓSEO Factores predisponentes Intervención

16 # 875. Body Composition (ACTG Study A5260s) Todd BrownN=331 pacientes naive DMO baja asociada a: más adiponectina, menos OPG, menos “lean mass”

17 #125LB. Switching from AZT/3TC to TVD on Bone Mineral Density (Sub-study of PREPARE Study) Aoife Cotter

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19 # 878. Switch from Tenofovir to Raltegravir (TROP Study). Mark BlochEstudio multicéntrico, no-randomizado. N= 37 pacientes con t-score <-1 SD en lumbar o femur. IP/r + TDF…  IP/r + RAL…

20 # 886. Vitamin D Insufficiency Is Associated with HIV Disease Progression and Death. Fiona Havers

21 TOXICIDAD RENAL Métodos diagnósticos Riñón y TDF

22 # 862. Validation of eGFR equations compared with isotopic GFR# 862. Validation of eGFR equations compared with isotopic GFR. Eiam-Ong. 99mTc DTPA plasma clearence GFR N=196 naive; N=186 ARV eGFR infraestima el GFR Cistatina C y MDRD  metodos más aproximados.

23 # 866. Baseline Creatinine-based eGFR and CC as Predictors of Clinical Events (SMART). Gregory LucasN=4613 pacientes (SMART con creatinina y cistatina C). Asociación eGFR con EKD-EPI con: - Mortalidad (n=92) - RCV (n=111) - Infec. oportunistas (n=118) Cistatina C tiene mejor asociación con mortalidad, evento Cv y IO que ecuación eGFR.

24 # 865. Exposure to ARV and the Risk of Renal Impairment ( D:A:D)# 865. Exposure to ARV and the Risk of Renal Impairment ( D:A:D). Lene Ryom pacientes con FGR normal en basal  2,1% progresaron a FGR<70.  0,6% a IRC (FGR<60) Pacientes con TDF, ATV i LPV progresaron más a “descenso de FGR”, como los factores riesgo tradicionales. Cambios de TDF, pero no de ATV o LPV. Monotorizar a éstos.

25 # 870. Immune Status Plays a Key Role in Renal Recovery in Patients with Tenofovir-related Nephrotoxicity. Anna Bonjoch.

26 Muchas gracias