VIH y edad Enric Pedrol Clotet Xarxa Sanitària i Social de Santa Tecla. Servei de Medicina Interna. Hospital de Sant Pau i Santa Tecla, Tarragona. Hospital.

Presentación del tema: "VIH y edad Enric Pedrol Clotet Xarxa Sanitària i Social de Santa Tecla. Servei de Medicina Interna. Hospital de Sant Pau i Santa Tecla, Tarragona. Hospital."— Transcripción de la presentación:

1 VIH y edad Enric Pedrol Clotet Xarxa Sanitària i Social de Santa Tecla. Servei de Medicina Interna. Hospital de Sant Pau i Santa Tecla, Tarragona. Hospital de El Vendrell, Tarragona. Hospital Lleuguer de Llevant, Tarragona Guatemala, 30 de septiembre de 2010

2 Life expectancy of individuals on combination antiretroviral therapy in high-incame countries: a collaborative analysis of 14 cohort studies (ART-CC)‏ The Lancet. Vol 372 July 26. 2008

3 Kirk and Goetz. Journal of American Geriatrics Society 2009 (57): 2129-2138 Epidemiology

4 Vigilancia Epidemiológica del VIH en España. Actualización 30 de junio 2009 Ministerio de Sanidad y Política Social. Nuevos diagnósticos de VIH. Distribución por edad y sexo. España. Datos de 12 CCAA *. Año 2008

5 Paciente de 73 años, sin hábitos tóxicos ni alergias conocidas y con AP de: - Apendicetomizado en la juventud. - Diagnosticado de Hernia de hiatus a los 44 años. - Fractura cubital a los 55 años. - Neumonía extrahospitalaria que no requirió ingreso a los 64 años. - Herpes zóster dorsal a los 69 años. - Faquectomía bilateral a los 71 años. CASO CLÍNICO (I)‏

6 Enfermedad actual (I): - Disnea progresiva de 19 días de evolución junto a síndrome febril de hasta 38ºC. Por dicho motivo, acudió a los 3 días del inicio de los síntomas a su médico de cabecera quién constató un paciente con un estado general conservado, con una frecuencia respiratoria de 15 x’ pero febricular (37,8ºC) y con tos no productiva; la auscultación respiratoria era normal. Por todo ello, se diagnosticó de infección respiratoria y se le prescribió tratamiento sintomático (antitérmico y antitusígeno). - A los 10 días del inicio del cuadro y al persistir la sintomatología (básicamente, la disnea había progresado algo, la febrícula resurgía al acabar el efecto del antitérmico y tenía ciertas dificultades para la ingesta) acudió al Servicio de Urgencias de su hospital de referencia. CASO CLÍNICO (II)‏

7 Enfermedad actual (I): - Disnea progresiva de 19 días de evolución junto a síndrome febril de hasta 38ºC. Por dicho motivo, acudió a los 3 días del inicio de los síntomas a su médico de cabecera quién constató un paciente con un estado general conservado con una freuencia respiratoria de 15 x’ pero febricular (37,8ºC) y con tos no productiva; la auscultación respiratoria era normal. Por todo ello, lo diagnosticó de infección respiratoria y le prescribió tratamiento sintomático (antitérmico y antitusígeno). - A los 10 días del inicio del cuadro y al persistir la sintomatología (básicamente la disnea había progresado algo, la febrícula resurgía al acabar el efecto del antitérmico y tenía ciertas dificultades para la ingesta) acudió al Servicio de Urgencias de su hospital de referencia. CASO CLÍNICO (II)‏ DISNEA + FIEBRE + TOS NO PRODUCTIVA - de forma prolongada -

8 Enfermedad actual (II): En selección de dicho centro se le constató: - Moderada afectación del estado general - 37,2ºC - FR: 18x’ - Subcrepitantes bibasales - Muguet Se le diagnosticó de sobreinfección respiratoria y se le pautó hidratación, paracetamol, un imidazol tópico y amoxicilina + ácido clavulánico (500/125 mg cada 8 horas). Se procedió al alta. CASO CLÍNICO (III)‏

9 Enfermedad actual (II): En selección de dicho centro se le constató: - Moderada afectación del estado general - 37,2ºC - FR: 18x’ - Subcrepitantes bibasales - Muguet Se le diagnosticó de sobreinfección respiratoria y se le pautó hidratación, paracetamol, un imidazol tópico y amoxicilina + ácido clavulánico (500/125 mg cada 8 horas). Se procedió al alta. CASO CLÍNICO (III)‏ MUGUET

10 - El 19° día de sintomatología y con una disnea de pequeños esfuerzos el paciente fue visitado domiciliariamente y remitido (“OD: descartar neumonía”) de nuevo a Urgencias de su Hospital de referencia. - En Urgencias se constató un paciente febril (38ºC), taquipneico (25 x’), taquicárdico (100 x’) y con afectación del estado general. - La auscultación respiratoria mostraba subcrepitantes bibasales. CASO CLÍNICO (IV)‏

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12 - Se realizó una analítica que reveló: - 3400 leucocitos (80% S, 8% L, 5% M, 5% E, 2% B)‏ - 125000 PQ - Hb: 10 (NN)‏ - GOT: 38 - CPK: 100 - Dímero-D: normal - Resto normal CASO CLÍNICO (V)‏

13 clinicaloptions.com/hiv HIV/AIDS Update From Mexico City 2008

14 clinicaloptions.com/hiv HIV/AIDS Update From Mexico City 2008

15 clinicaloptions.com/hiv HIV/AIDS Update From Mexico City 2008

16 - DIAGNÓSTICOS: - SIDA (VIH+ Estadío C3) - Pneumocystis Jirovecii - Muguet CASO CLÍNICO (VI)‏

17 FBS: P. Jirovencii CD4: 73 CV-VIH: 800000 LDH: 800 VIH+ (ELISA + WB)‏

18 clinicaloptions.com/hiv HIV/AIDS Update From Mexico City 2008

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20 BK esputo + Cultivo de Lowenstein + Auramina

21 Cryptococcus Neoformans

22 Adults and Children Estimated to Be Living With HIV, 2008 North Africa and Middle East 380,000 Sub-Saharan Africa 22 million Eastern Europe and Central Asia 1.5 million Oceania 74,000 Caribbean 230,000 Southern and Southeast Asia 4.2 million Latin America 1.7 million UNAIDS, 2008. Available at: http://www.unaids.org. East Asia 740,000 North America 1.2 million Western/ Central Europe 730,000

23 clinicaloptions.com/hiv HIV/AIDS Update From Mexico City 2008 SMART: BL Characteristics Lundgren J, et al. IAC 2008. Abstract THAB0305.

24 E. Martínez et al: 12 CROI, Boston 2005. Póster nº870 CARDIOVASCULAR RISK FACTORS *Defined by prior diagnosis, specific therapies, or abnormal BP or glucose values #Defined by abnormal value for triglycerides, total cholesterol, or HDL-cholesterol Men ≥ 45 years26.4% of men Women ≥ 55 years3.5% of women Tobacco smoking (current)64.4% Family history of CHD11.1% Hypertension*22.5% Diabetes mellitus*8.0% BMI ≥30 kg/m 2 5.8% Metabolic syndrome 9.6% Previous cardiovascular disease3.4% Lipid-lowering therapy6.2% Lipodystrophy36.9% Total cholesterol >200 mg/dL35.4% HDL cholesterol <40 mg/dL26.7% LDL-cholesterol > 130 mg/dl 18.0% No-HDL cholesterol >160 mg/dL22.9% Triglycerides >200 mg/dL27.4% Dyslipidemia #62.4%

25 HIV-1 infection in subjects older than 70: a multicenter cross-sectional assessment in Catalonia, Spain Mothe B, Pérez I, Domingo P, Podzamczer D, Ribera E, Viladés C, Vidal F, Dalmau D, Pedrol E, Negredo E, Moltó J, Paredes R, Pérez-Álvarez N, Gatell JM, Clotet B IAS-Cape Town-2009 & Current HIV Research 2009; 7: 597-600. 8 Centros (7 Barcelona + 1 Tarragona)‏ N: 179: 1,5% de la serie (11815 pacientes seguidos en 2008)‏ 76% ♂ Edad media: 74,6 años 87% contagio vía sexual (HTSx: 49,7%; HMX: 37.9%; UDVP: 0,6%)‏ 69% diagnosticados en la sexta década < 200 CD4 cél/mm3: 52% (cohorte comparativa: 34%) (media al diagnóstico: 190)‏ CV-VIH media: 148000 cp/ml (57% > 100000 cp/ml)‏ Coinfección VHB/C: 9,7%

26 HIV-1 infection in subjects older than 70: a multicenter cross-sectional assessment in Catalonia, Spain Mothe B, Pérez I, Domingo P, Podzamczer D, Ribera E, Viladés C, Vidal F, Dalmau D, Pedrol E, Negredo E, Moltó J, Paredes R, Pérez-Álvarez N, Gatell JM, Clotet B IAS-Cape Town-2009 & Current HIV Research 2009 7: 597-600. 8 Centros (7 Barcelona + 1 Tarragona)‏ N: 179: 1,5% de la serie (11815 pacientes seguidos en 2008)‏ 76% ♂ Edad media: 74,6 años 87% contagio vía sexual (HTSx: 49,7%; HMX: 37.9%; UDVP: 0,6%)‏ 69% diagnosticados en la sexta década < 200 CD4 cél/mm3: 52% (cohorte comparativa: 34%) (media al diagnóstico: 190)‏ CV-VIH media: 148000 cp/ml (57% > 100000 cp/ml)‏ Coinfección VHB/C: 9,7% Vía sexual y Diagnóstico tardío

27 NA-ACCORD: Survival Benefit With Earlier vs Deferred HAART (at 350-500 cells/mm 3 )‏ Kitahata MM, et al. ICAAC/IDSA 2008. Abstract H-896b.  Increased relative hazard of death with deferral of HAART remained unchanged when adjusted for IDU or for HCV coinfection, which were both independent predictors of mortality Parameter Associated With Risk of Death Relative Hazard (95% CI)‏ Older age (per 10 years)‏ BL CD4+ cell count (per 100 cells/mm 3 increase)‏ 1.6 1.02.50.1 Deferral of HAART until < 350 cells/mm 3 (vs starting at 350-500 cells/mm 3 )‏ Female sex 0.9 1.7 1.1 P Value <.001.290 <.001.083 Early Initiation of HAART Reduces Risk of Death by 70%

28 Factors associated with late presentation Generally related to… – those who are not perceived, or who do not perceive themselves, to be at high risk of infection. – those who are not actively offered HIV testing. – marginalized groups. More common in: – heterosexuals in comparison with MSM or IDUs*. – older age. – immigrants. – lower socioeconomic status. – people living in low HIV prevalence areas. * Although IDUs are more likely to experience delay in presenting for clinical care once diagnosed Girardi E, et al. J Acquir Immune Defic Syndr, 2007

29 Late presentation: importance For the individuals: –Generates greater morbidity and mortality: More likely to die of AIDS defining illness: 77% of all AIDS related deaths occur in late presenters 1. Risk of OI and death increases as immune function deteriorates: 24% of all HIV positive deaths due to late presentation 2. For public health: –Represents a challenge to prevention of onward transmission: Estimated transmission is 3.5 times higher among persons who are unaware of their infection 3. New sexual infections could be reduced by 30% if all infected persons learn of their HIV status and adopt adequate behaviour 3. 1 Ciancio B et al, 2006. 2 BHIVA, 2007. 3 Marks G et al, AIDS 2006.

30 Patients (%) presenting at late stage: selected studies 1. Stöhr W, et al. HIV Med 2007;8(3):135–141 2. Sabin C, et al. AIDS 2004;18(16):2145–2151; 3. ART-LINC and ART-CC groups. Lancet 2006;367:817–824; 4. Delpierre C, et al. Int J STD AIDS 2007;18(5):312–317; 5. Manzardo C, et al. J Acquir Immune Defic Syndr 2007;46(Suppl 1):S9–18; 6. Wolbers M, et al. HIV Med 2008;9(6):397–405; 7. Brannstrom J, et al. Int J STD AIDS 2005;16(10):702–706; 8. Manavi K, et al. Int J STD AIDS 2004;15(12):811−814; 9. Sullivan A, et al. BMJ 2005;330(7503):1301−1302; 10. Giratdi E, et al. J Acquire Immune Defic Syndr 2004;36(4)951–959 20 1 VL >100 000 copies/mL 23−45 3,5,7,10 Clinical criteria 15−31 2,3 CD4 cell count <50/  L 23−73 1,3,4,5,8,9 CD4 cell count <200/  L Patients (%)‏ Late presentation is most common in heterosexual men 2,5,7,8, women 2,5,8, older patients 5,6,7, African Americans/people of non-white race 2,5,6, patients of foreign origin 5,7 and low-income countries 3 The incidence of late presentation appears to be increasing in some countries (eg Spain, Italy) but not in others (eg UK) 5

31 Late diagnosis and age There is an over-representation of older persons in late presenting patients 1,2 ► Clinicians less likely to suspect HIV in older patients 3,4 ► Older people are more likely to attribute HIV symptoms to other illnesses or the normal ageing process 5 1. Sullivan AK et al., BMJ 2005, 330:1301–2. 2. Chadborn TR et al., AIDS 2005, 19:513–20. 3. el-Sadr W and Gettler J, Arch Intern Med 1995, 155:184–6. 4. Inelmen E.M. et al., Geriatrics 2005, 60:26–30. 5. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents 2009. www.aidsinfo.nih.gov/contentfiles/adultandadolescentGL.pdf. Accessed March 2010.

32 HIV-1 infection in subjects older than 70: a multicenter cross-sectional assessment in Catalonia, Spain Mothe B, Pérez I, Domingo P, Podzamczer D, Ribera E, Viladés C, Vidal F, Dalmau D, Pedrol E, Negredo E, Moltó J, Paredes R, Pérez-Álvarez N, Gatell JM, Clotet B IAS-Cape Town-2009 & Current HIV Research 2009 7: 597-600. 154 pacientes (86%) presentaban una co- morbilidad por lo menos: – 54% Dislipemia (cohorte comparativa –cc-: 28%)‏ – 36% HTA – 30% hiperglicemia/diabetes (cc: 17%)‏ – 23% Enfermedad cardiovascular – 18% Insuficiencia renal crónica – 17% Neoplasia (actual o anterior) (cc: 7%)‏ – 11% Deterioro cognitivo – 58% Lipodistrofia

33 HIV-1 infection in subjects older than 70: a multicenter cross-sectional assessment in Catalonia, Spain Mothe B, Pérez I, Domingo P, Podzamczer D, Ribera E, Viladés C, Vidal F, Dalmau D, Pedrol E, Negredo E, Moltó J, Paredes R, Pérez-Álvarez N, Gatell JM, Clotet B IAS-Cape Town-2009 & Current HIV Research 2009 7: 597-600. 154 pacientes (86%) presentaban una co- morbilidad por lo menos: – 54% Dislipemia (cohorte comparativa –cc-: 28%)‏ – 36% HTA – 30% hiperglicemia/diabetes (cc: 17%)‏ – Enfermedad cardiovascular (23%)‏ – Insuficiencia renal crónica (18%)‏ – Neoplasia (actual o anterior): 17% (cc: 7%)‏ – Deterioro cognitivo: 11% – Lipodistrofia: 58% Co-Morbilidades

34 Risk of cardiovascular disease increased in HIV-infected persons Triant VA et al. J Clin Endocrinol Metab 2007 RR: 1.75 (95% CI: 1.51-2.02; P <.0001)* *Adjusted for age, sex, race, hypertension, diabetes, dyslipidemia. 0 10 20 30 40 50 60 70 80 90 18-3435-4445-5455-6465-74 MI Events per 1000 Person-Yrs Age Group (Yrs)‏ 4.65 10.13 18.74 33.39 77.68 0.88 3.34 7.56 14.78 24.47 100 HIV positive HIV negative 2-fold higher risk of ischemic heart disease in HIV-infected patients on ART compared with adjusted uninfected population Obel N et al. Clin Infect Dis 2007

35 Non-modifiable Risk Factors Results from the D:A:D Study Smith C, et al. CROI 2009. Oral presentation 145

36 NNDS-Relacionadas con… -10% de los pacientes VIH desarrollan cáncer y el 71% de estos cánceres serán NNDS. -Se relaciona su aparición con la raza blanca y la edad. Crum-Cianflone N et al. AIDS 2009 -Se han dado diversas explicaciones para justificar este aumento de incidencia: mayor supervivencia (mayor edad (mayor impacto de factores de riesgo clásicos para cáncer) y alta incidencia de virus potencialmente oncogénicos (virus del papiloma humano, virus de Epstein-Barr y virus de la hepatitis C por ejemplo).

37 SCOPE: Decline in eGFR in HIV improved by ART Baseline characteristics (Mean or %)‏ Age (years)‏45.3 Female13.2% Race White50.7% Black28.5% Hispanic9.6% CD4 Count (cells/mm 3 )‏434 HIV RNA (log 10 c/mL)‏3.1 Observation Time (years)‏2.7 Number GFR Measurements10 Multivariable Model Fully adjusted effect on GFR slope (mL/min/1.73m 2 per year)‏ Age (years)‏-0.7 (-0.9, - 0.5)‏ Female-1.8 (-3.1, -0.6)‏ Diabetes-4.4 (-8.4, -0.4)‏ Hyperlipidaemia-2.7 ( -4.7, -0.7)‏ Overall unadjusted rate of GFR: -2.6 (95% CI -3.0, -2.1) mL/min/1.73m 2 per year (age expected rate 0.4)‏ Average rate of GFR decline (mL/min/1.73m 2 per year)‏ pre-ART: -4.7 (95% CI -6.7, -2.6)‏ post-ART: -1.9 (95% CI -3.7, -0.1) Improvement in eGFR not evident in ‘blippers’ Untreated noncontrollers showed most impact on eGFR; Untreated controllers least Choi A, et al. CROI 2009. Abstract 38 Assessment of renal function in 615 HIV+ pts enrolled in the SCOPE cohort

38 HIV-1 infection in subjects older than 70: a multicenter cross-sectional assessment in Catalonia, Spain Mothe B, Pérez I, Domingo P, Podzamczer D, Ribera E, Viladés C, Vidal F, Dalmau D, Pedrol E, Negredo E, Moltó J, Paredes R, Pérez-Álvarez N, Gatell JM, Clotet B IAS-Cape Town-2009 & Current HIV Research 2009 7: 597-600. Polifarmacia: además de los antirretrovirales: toman una media de 2.97 fármacos (límites: 1-10): – Hipolipemiantes (19%)‏ – Antihipertensivos (16%)‏ – ADO/insulina (11%)‏ – Antiagregantes (11%)‏ – Psicofármacos (6%)‏ – Antiácidos (3%)‏ – Nitratos (2%)‏ – Anticoagulantes orales (2%)‏ – Allopurinol (2%)‏ 99% en HAART

39 HIV-1 infection in subjects older than 70: a multicenter cross-sectional assessment in Catalonia, Spain Mothe B, Pérez I, Domingo P, Podzamczer D, Ribera E, Viladés C, Vidal F, Dalmau D, Pedrol E, Negredo E, Moltó J, Paredes R, Pérez-Álvarez N, Gatell JM, Clotet B IAS-Cape Town-2009 & Current HIV Research 2009 7: 597-600. Polifarmacia: además de los antirretrovirales: toman una media de 2.97 fármacos (límites: 1-10): – Hipolipemiantes (19%)‏ – Antihipertensivos (16%)‏ – ADO/insulina (11%)‏ – Antiagregantes (11%)‏ – Psicofármacos (6%)‏ – Antiácidos (3%)‏ – Nitratos (2%)‏ – Anticoagulantes orales (2%)‏ – Allopurinol (2%)‏ 99% en HAART POLIMEDICACIÓN

40 Polypharmacy in older patients Older patients often take concurrent medications for other conditions Vigilance is needed to avoid drug–drug interactions ► Overlapping toxicities ► Altered plasma drug levels, necessitating dose adjustments ► Increased metabolism of ARVs, decreasing bioavailability Commonly used drugs that may interact include ► Statins, antiarrhythmics, gastric acid inhibitors, warfarin, SSRIs, erectile dysfunction agents, anticonvulsants Simone MJ et al., Geriatrics 2008, 63:6–12.

41 > 55 años: 30 > 60 años: 16 > 65 años: 8 > 70 años: 5 Cerca del 10% de nuestros pacientes

42 Circunstancias que influyen en la transmisión de la infección HIV en pacientes > 50 a.  Desconocimiento de los factores de riesgo de transmisión inf. HIV.  Menor tasa de empleo de preservativo  Atrofia vaginal en mujeres de edad facilita la infección  Falta de percepción del personal médico del riesgo de inf. VIH en paciente de avanzada edad.  Baja tasa de utilización del test de detección VIH  Vergüenza-miedo a la estigmatización Onen N.F. Missouri Medicine. July/Agost 2009. 100 (4): 269-273

43 A growing proportion of HIV diagnoses are in the over 50s 12.9% of newly reported cases of HIV infection in Western Europe in 2007 were in people aged 50 years or older Lazarus JV and Nielsen KK, HIV Medicine 2010; in press % newly diagnosed HIV patients aged 50+ 0 2 4 6 8 10 12 14 20032004200520062007 Western Europe Central Europe Eastern Europe

44 Persons 50+ more often present with symptomatic HIV disease Clinical stage at presentation of non-IDUs since 1990 Unpublished Swiss Cohort HIV Study Ledergerber B et al., 15 th CROI 2008, Boston, Massachusetts, USA. Abstract 108. <3030–3940–4950+ 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Age Group CDC-Stage n=2199327717211082 C B A

45 ...and more often with a lower CD4 cell count CD4 cell count at presentation of Caucasian heterosexually-infected persons (n=2877)‏ Unpublished Swiss Cohort HIV Study <30 30-39 40-49 50+<30 30-3940-49 50+<30 30-39 40-49 50+<30 30-39 40-49 50+ 0 100 200 300 400 500 600 700 800 1990–19941995–19981999–20022003–2007 Median (IQR) CD4 cells [mm 3 ] at presentation Age group Ledergerber B et al., 15 th CROI 2008, Boston, Massachusetts, USA. Abstract 108.

46 Aspects of Personalised HIV Medicine that can be Used to Optimise Therapeutic Outcomes Martinez E. and Nolan P. European Infectious Diseases. In press Summary of Patient Considerations for Optimising Therapeutic Outcome

47 Why do older patients appear to be at higher risk of HIV disease progression? Tendency to be diagnosed at a later stage More rapid progression in natural course of HIV Higher risk of complications Greater potential for worsening ARV toxicity Slower immunological response to HAART ► Despite superior virological responses in patients >50 years than in younger patients (usually attributed to better adherence to medication in the older population)‏ Grabar S, et al., J Antimicrob Chemother 2006, 57:4–7.

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50 Sophie Grabar. AIDS 2004, 18: 2029-2038 Mean increase in CD4 cell after HAART iniciation acording to the age and HIV RNA level. Inmunological and clinical responses to highly active antiretroviral therapy over 50 years of age. Results from the French Hospital Database on HIV

51 Guideline Recommendations for Initiation of ART in Established HIV Infection DHHSIAS-USA Symptomatic HIV disease Asymptomatic; CD4+ count < 350 cells/mm 3 Asymptomatic; CD4+ count > 350 cells/mm 3 if: - Pregnant women - HBV co-infection - HIV-associated nephropathy - Other considerations Age Co-morbidities CD4+ cell decline Serodiscordant relationships Symptomatic HIV disease Asymptomatic; CD4+ count < 350 cells/mm 3 Asymptomatic; CD4+ count > 350 cells/mm 3 if: - HIV-1 RNA > 100,000 copies/mL - CD4+ cell count decline > 100 cells/mm³/year - HBV co-infection - HCV co-infection - Cardiovascular disease - HIV-associated nephropathy - Other considerations Mother-to-child transmission Serodiscordant relationships DHHS guidelines. Available at: http://www.aidsinfo.nih.gov. Accessed January 12, 2009 Hammer SM, et al. JAMA. 2008; 300:555-570.

52 Symptomatic HIV disease Asymptomatic; CD4+ count < 350 cells/mm 3 Asymptomatic; CD4+ count > 350 cells/mm 3 if: - AIDS diagnosis; any HIV- related co-morbidity - Low CD4% (<14%)‏ - Established CV disease or very high risk of CV events - Hepatitis B or C-coinfection BHIVA 2008EACS 2008GESIDA 2009 Symptomatic HIV disease Asymptomatic; CD4+ count < 350 cells/mm 3 Asymptomatic; CD4+ count > 350 cells/mm 3 if: - Viral load > 10 5 c/mL - CD4 decline >50- 100/mm 3 /year - Age > 55 - Hepatitis C co-infection Infección sintomática Infección asintomática; CD4+ count < 350 cells/mm 3 Infección asintomática; CD4+ count >350 cells/mm 3 si: - Cirrosis hepática - Hepatitis crónica por virus C - Hepatitis B con indicación de tratamiento - CV > 10 5 c/mL - CD4 < 14% - Edad > 55 años - Riesgo CV elevado - Nefropatía VIH 1 European AIDS Clinical Society (EACS). Guidelines for the clinical management and treatment of HIV infected adults in Europe [on line]. Available from URL: http://www.eacas.eu/guide/index.htm [Accessed October 7, 2008]; 2 Gazzard BG et al. British HIV Association (BHIVA) guidelines forhttp://www.eacas.eu/guide/index.htm the treatment of HIV-1-infected adults with antiretroviral therapy 2008. HIV Med 2008; 9:563-608; 3 GESIDA/PNS 2009. [on line]. Available from URL: www.gesida.seimc.org/index.asp# [Acceso Febrero, 2009].www.gesida.seimc.org/index.asp# Guideline Recommendations for Initiation of ART in Established HIV Infection

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54 Why might age impact on HAART tolerability? Pharmacological handling: ► Decreased hepatic and renal function with age ► Decreased CYP450 concentrations 1 Predisposition to toxicities: ► Increased cardiovascular risk ► Lower bone mineral density ► Increased renal disease Polypharmacy Patient perception of health and medicines: 2 ► Increased adherence, stoicism ► Less concerns about theoretical toxicity ► Less concerns with experiencing side-effects 1. Sotaniemi EA et al., Clin Pharmacol Ther 1997, 61:331–9. 2. Sherr et al., Psychology, Health & Medicine 2009,14:273–279.

55 Age and toxicity in the first year of HAART (UK-CHIC)‏ 8,708 treatment-naïve patients initiating HAART between 1998–2005 in 13 UK centres 2,650 (30%) discontinued at least one drug for non-virological failure reasons Discontinuing was associated with: ► Younger age (<30; RH 1.12, 95% CI 1.01, 1.24)‏ ► Older age (>50; RH 1.14, 95% CI 1.00, 1.31)‏ Strong association between older age and: ► Increased cholesterol ► Decreased haemoglobin ► Increased triglycerides (although triglycerides were also higher in older patients before HAART)‏ Sabin CA et al., HIV Medicine 2009, 10:35–43.

56 ARV treatment outcomes and age-related co-morbidities in older vs. younger patients 48 weeks of HAART in 159 older patients and 118 younger controls with comparable HIV stage, baseline CD4 count and viral load CV and endocrine metabolic disorders were significantly more frequent in older group ► 33 CV disorders in older patients vs. 2 in younger group ► 16 endocrine metabolic disorders in older patients vs. 0 in younger patients Significantly higher relative risk of adverse events on therapy in older patients: ► Moderate to severe renal or liver toxicities were recorded in 21 and two older patients, respectively but not in controls ► Tolerability of ART did not differ between older patients and controls Orlando G, et al. HIV Medicine 2006, 7:549–557.

57 Adherence in younger vs. older HIV patients 0 10 20 30 40 50 60 70 80 90 100 78.3 <50 87.5 ≥ 50 Patient age, years Proportion of patients adherent to therapy (%)‏ Hinkin CH, et al., AIDS 2004, 8 (Suppl. 1):S19–S25 p=0.01

58 Gracias por su atención S. Ruiz M. Tasias A. Delegido E. Pedrol Unitat VIH