INFECCI N POR HIV

1. INFECCIÓN POR HIV/SIDAEMERGENCIAS Dr. Cuatz, Daniel Infectología H. Fernández

3. Argentina: Distribución de casos de SIDA diagnosticados según vía de Transmisión Año 1982 -2005

4. Argentina: Distribución de VIH diagnosticados según vía de Transmisión 2000-2005

5. Incidencia de Infecciones Oportunistas en pacientes con <100 CD4/mm3

6. In this slide you have the causes of death in these patients. It is very evident that HIV-related mortality, in orange, has decreased from 80% in 1997 to 20% in 2001. However, non-HIV related mortality has simultaneously increased and the most important cause in the last year was End Stage Lived Disease, in blue, which increased from 8% in 1997 to 30% in 2001. Next slide,In this slide you have the causes of death in these patients. It is very evident that HIV-related mortality, in orange, has decreased from 80% in 1997 to 20% in 2001. However, non-HIV related mortality has simultaneously increased and the most important cause in the last year was End Stage Lived Disease, in blue, which increased from 8% in 1997 to 30% in 2001. Next slide,

7. Distribution of PCP, Toxoplasmosis and Tuberculosis in Reported AIDS Cases to MOH (Brazil, 1981-2001) In terms of morbidity reduction, we observed that the occurrence of HIV-related opportunistic infections was declined in 60-80%. As you can see in this slide, this downshift in the incidence curve of major opportunistic diseases, like Pneumocystis carinii pneumonia, toxoplasmosis and tuberculosis have occurred particularly after the availability of HAART. Moreover, it was observed a change in the profile of HIV health care services with a significant increase of the demand for outpatient services, home care and day-hospital services. However it is important to say that besides this striking reduction, tuberculosis continue to be the most important cause of death among HIV+ patients, and more recently, hepatitis C and some kinds of cancers are becoming a big concern. In terms of morbidity reduction, we observed that the occurrence of HIV-related opportunistic infections was declined in 60-80%. As you can see in this slide, this downshift in the incidence curve of major opportunistic diseases, like Pneumocystis carinii pneumonia, toxoplasmosis and tuberculosis have occurred particularly after the availability of HAART. Moreover, it was observed a change in the profile of HIV health care services with a significant increase of the demand for outpatient services, home care and day-hospital services. However it is important to say that besides this striking reduction, tuberculosis continue to be the most important cause of death among HIV+ patients, and more recently, hepatitis C and some kinds of cancers are becoming a big concern.

8. Argentina: evolución de la tasa de mortalidad por VIH/SIDA y tasa de incidencia de Sida, 1990-2002 

9. Epidemiology of AIDS : Changing Trends New treatments - PCP prophylaxis Reduced incidence Lengthened disease-free intervals Prolonged life expectancy

10. Progress in ART Scale Up A remarkable achievement 1.6 M people on ART 24% of 6.8 M in need; M=F 21 countries treating >50% in need; capacity growing Excellent outcomes in large cohorts of adults & children $8.3 B mobilized G-8 commitment: Universal access to prevention and care by 2010 Remaining challenges 10-20% ART mortality in 1st year Majority present with advanced disease (73% w/ CD4 < 100) < 5% of HIV+ children on ART < 10% of HIV+ pregnant women receive PMTCT Less access and ART for IDUs Human resource, skill deficits Labs, toxicities, costs Sustainability; $25B needed G8: Canada, France, Germany, Italy, Japan, Russia, the United Kingdom, and the United States. Extracted from 2006 Report on the global AIDS epidemic (UNAIDS, 2006) http://www.unaids.org G8: Canada, France, Germany, Italy, Japan, Russia, the United Kingdom, and the United States. Extracted from 2006 Report on the global AIDS epidemic (UNAIDS, 2006) http://www.unaids.org

12. Integration of Clinical Data: CD4 count CD4 > 450 Bacterial infections Mycobacterium TB lung cancer (?) CD4 200-450 Recurrent bacterial infections Mycobacterium TB Lymphoma Lymphoproliferative disorders

13. Bacterial Infection: Pneumonia Incidence of pneumonia 5x non-AIDS 2 pneumonic episodes in 1 year = onset of AIDS Multilobar / bilateral disease 20% incidence recurrent infection with CD4 < 200

15. Integration of Clinical Data: CD4 count CD4 < 200 PCP Disseminated TB CD4 <100 PCP Pseudomonas Atypical mycobacterium CMV Fungal infection Lymphoma Kaposi’s sarcoma

16. PCP: CXR Appearances varied Symmetric perihilar interstitial / granular or ground glass pattern commonest….

20. PCP: Pneumothorax

21. Diagnosis Classical X-ray appearances of PCP are diffuse bilateral interstitial or alveolar shadowing. To confirm PCP, induced sputum can be performed or bronchoscopy with lavage (90%) (higher diagnostic sensitivity but also more invasive)

22. Mortality The overall mortality is 15-20 %. This has been reduced by the use of steroids Mortality for first, second and third episode of PCP in a patient have been shown to be similar

23. Mortality Mortality increases with age, longer time infected with HIV, PaO2<8kPa at admission, severe acute respiratory failure (PaO2/FiO2<20 kPaO2), additional pulmonary infections, mechanical ventilation, raised LDH.

24. Mortality in ventilated patients The overall mortality of patients admitted to intensive care was 28% rising to 79-81.9% if ventilation was required. Mortality was about 50 percent in those that were placed on ventilation early but reached almost 100 percent when it was started after a week of beginning of treatment

25. Methods of respiratory support High flow oxygen should be given via standard masks and oxygen saturation should be monitored closely. CPAP: PCP is an ideal condition for the use of CPAP because patients do not produce large amounts of sputum. This method delays or avoids the use of endotracheal ventilation.

27. Effects of HIV on Tuberculosis More likely: Infection after exposure 10-20% vs 5-10% Progressive primary disease after infection 30% vs 5-10% Reactivation of latent infection 5-10% annual vs 5-10% lifetime Reinfection with new strain Less cavitation and atypical chest x-ray appearance with lower CD4 count

28. Tendencia de la TB asociada al sida. España (1995-2003)

32. Global prevalence of MDR-TB MDR = resistant to at least isoniazid and rifampicin While the evidence is still limited, it appears that in other regions of the world the problem is restricted to selected countries. These include parts of China and India in Asia, Ivory Coast, Mozambique, and South Africa in Africa, and the Dominican Republic and Peru in the Americas. Right graphic shows a mathematic model for countries not reporting TB statistics. This model has recently estimated the magnitude of MDR-TB globally, suggesting that 3% (273 000, 95% confidence intervals: 185 000 and 414 000) of all new estimated tuberculosis cases were MDR-TB in 2000 Two-thirds of the world countries and, more importantly, half of the 22 high-burden TB countries, where 80% of the incidence of TB is generated, have not yet provided representative data that could be generalized with certain degree of confidence. MDR = resistant to at least isoniazid and rifampicin While the evidence is still limited, it appears that in other regions of the world the problem is restricted to selected countries. These include parts of China and India in Asia, Ivory Coast, Mozambique, and South Africa in Africa, and the Dominican Republic and Peru in the Americas. Right graphic shows a mathematic model for countries not reporting TB statistics. This model has recently estimated the magnitude of MDR-TB globally, suggesting that 3% (273 000, 95% confidence intervals: 185 000 and 414 000) of all new estimated tuberculosis cases were MDR-TB in 2000 Two-thirds of the world countries and, more importantly, half of the 22 high-burden TB countries, where 80% of the incidence of TB is generated, have not yet provided representative data that could be generalized with certain degree of confidence.

33. IRIS with TB Median 2-4 weeks after starting HAART Up to 1/3 cases > if nadir CD4 <50 > if brisk CD4 response Focal disease at/away from original site Treatment steroids/NSAIDS Also recognised in HIV –ve but < common

34. OI’s: Viruses Herpes: CMV, HSV, Varicella, EBV, HHV-8 CMV Commonest viral pathogen Latent infection in 90% of HIV +ve pt’s CD4 < 60 Retinitis, colitis, encephalitis PM series: isolated from 70%, of whom pneumonitis in 80%# (# Wallace, Chest 1987 )

36. CMV: Pneumonitis Associated with KS & PCP prophylaxis Increasing incidence Underdiagnosed (25% premortem) ? Organism detection - lung Bx TBNA & cultures unreliable

47. Hipersensibilidad por Abacavir Pancreatitis Acidosis Láctica Hepatitis Síndrome de Stevens-Johnson Toxicidad por ARVCompromete la vida inmediatamente

48. Toxicidad Asociadada a INTR

49. Síndrome de Stevens-Johnson

50. Síndrome de Stevens-Johnson

51. Reacciones por Hipersensibilidad por Abacavir Comienzo entre 3-42 días (Mediana: 9 días) Incidencia: 4% Características: (Por lo menos 2) Fiebre, astenia Tos, Faringitis, Taquipnea Náuseas, Vómitos +/- Rash NO RE-EXPONER !!!

52. Hipersensibilidad por Abacavir al Re-Exponer n=112 Síntomas que reaparecen en horas Reacción similar a la original Más Severa: Hipotensión 24% vs 5% Taquicardia 11% vs 1% Distress respiratorio 6%

53. Síndromes Clínicos Myopatía Cardiomiopatía Neuropatía Periférica Hiperlactatemia: AG-Acidosis láctica Esteatosis Hepática Pancreatitis Lipoatrofia

54. Síntomas Asociados a Hiperlactatemia

55. Síntomas en 7/10 pacientes con Hiperlactatemia arterial (>2.5 mmol)

56. Acidosis láctica Inducida por INRT I. Moderada (1-5 mmol/dL): Fatiga Náuseas Dolor Abdominal Aumento de Transaminasas. Reversible II: Severa (>5mmol/dL): Fallo Hepático 1.3-8.4/1000 individuos/año Alta Mortalidad

57. Toxicidad: Interacciones El más poderoso inhibidor de la Cyp 450-3ª es un ARV: Ritonavir El efecto se produce con “Baby dose”

60. http://clinicaloptions.com/hiv D:A:D—Prolonged Antiretroviral Exposure and Myocardial Infarction The reason for increasing concern about dyslipidemia and other metabolic complications of HIV is the potential that these complications may be associated with increased risk of cardiovascular disease and, in particular, myocardial infarction. This increased risk was first strongly suggested in a study published a few years ago, the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study, which indicated potential for increased risk of cardiovascular disease and myocardial infarction with increasing exposure to antiretroviral therapy. Updated data from this large cohort were presented at CROI, and continue to show evidence of increased risk of myocardial infarction per year of exposure to antiretroviral therapy. For more information, please go online to: http://clinicaloptions.com/hiv/conf/croi2005/cs/42.asp The reason for increasing concern about dyslipidemia and other metabolic complications of HIV is the potential that these complications may be associated with increased risk of cardiovascular disease and, in particular, myocardial infarction. This increased risk was first strongly suggested in a study published a few years ago, the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study, which indicated potential for increased risk of cardiovascular disease and myocardial infarction with increasing exposure to antiretroviral therapy. Updated data from this large cohort were presented at CROI, and continue to show evidence of increased risk of myocardial infarction per year of exposure to antiretroviral therapy. For more information, please go online to: http://clinicaloptions.com/hiv/conf/croi2005/cs/42.asp

61. http://clinicaloptions.com/hiv Updated analysis shows continuing increase in risk with longer duration[1] Increased risk partially but not completely explained by dyslipidemia However, trend for decreasing MI incidence from 2000-2003 after adjusting for ? smoking, ? lipid-lowering therapy[2] D:A:D—Prolonged Antiretroviral Exposure and Myocardial Infarction Further analyses of the D:A:D study continue to show that even when appropriate controls for other cardiovascular risk factors are included in the analysis, each additional year of antiretroviral therapy is associated with an increased risk of myocardial infarction. In the model shown in the slide, the adjusted relative risk was 1.17, or approximately 17% increased risk per year on antiretroviral therapy. Other important risk factors in this model were age, male sex, history or family history of cardiovascular disease, and smoking—all recognized as important risk factors for cardiovascular disease. Further analyses of this cohort suggest that the increased risk associated with antiretroviral therapy is partially, but not completely, explained by dyslipidemia. Of interest, in an additional analysis presented at this meeting, it was suggested that changes in the cohort—including less smoking and more use of lipid-lowering therapy—may be associated with decreasing incidence of myocardial infarction over the last 4 years. This finding perhaps reflects the fact that physicians caring for HIV-positive patients, and the patients themselves, are increasingly aware of the risks associated with myocardial infarction. For more information, please go online to: http://clinicaloptions.com/hiv/conf/croi2005/cs/42.asp http://clinicaloptions.com/hiv/conf/croi2005/cs/866.aspFurther analyses of the D:A:D study continue to show that even when appropriate controls for other cardiovascular risk factors are included in the analysis, each additional year of antiretroviral therapy is associated with an increased risk of myocardial infarction. In the model shown in the slide, the adjusted relative risk was 1.17, or approximately 17% increased risk per year on antiretroviral therapy. Other important risk factors in this model were age, male sex, history or family history of cardiovascular disease, and smoking—all recognized as important risk factors for cardiovascular disease. Further analyses of this cohort suggest that the increased risk associated with antiretroviral therapy is partially, but not completely, explained by dyslipidemia. Of interest, in an additional analysis presented at this meeting, it was suggested that changes in the cohort—including less smoking and more use of lipid-lowering therapy—may be associated with decreasing incidence of myocardial infarction over the last 4 years. This finding perhaps reflects the fact that physicians caring for HIV-positive patients, and the patients themselves, are increasingly aware of the risks associated with myocardial infarction. For more information, please go online to: http://clinicaloptions.com/hiv/conf/croi2005/cs/42.asp http://clinicaloptions.com/hiv/conf/croi2005/cs/866.asp

63. Incidencia de Infecciones Oportunistas en pacientes con <100 CD4/mm3

64. La Terapia ARV exige un Balance entre la Eficacia y la Toxicidad del Régimen Regimenes Fáciles para el Paciente Son Fáciles para el Virus Regimenes Duros para el Virus Son Demasiados Duros para los Pacientes