ANTEA WORLDWIDE Palliative Care Conference SESSION “Non Cancer Palliative Care” November 13, 2008 The Need for Palliative Care among HIV-Infected Persons in the HAART Era Fabrizio Palmieri National Institute for Infectious Diseases “L. Spallanzani”- IRCCS, Rome

Trends in annual-adjusted number of deaths for AIDS in Italy, 1982-2007 Source COA-ISS 279 == Introduction of Highly Active Anti- Retroviral Therapy (HAART)

AIDS in the pre-HAART era AIDS was a rapidly fatal, acute infectious disease The usual prognosis was death 6-12 months after AIDS diagnosis . The only available treatments were addressing symptoms, prevention and treatment of opportunistic infections, and providing good end-of-life care. Emphasis on preventing and treating opportunistic infections and on providing palliative care.

AIDS was a rapidly fatal, acute infectious disease

The usual prognosis was death 6-12 months after AIDS diagnosis .

The only available treatments were addressing symptoms, prevention and treatment of opportunistic infections, and providing good end-of-life care.

Emphasis on preventing and treating opportunistic infections and on providing palliative care.

Trajectory of AIDS decline in the pre-HAART era Death Severity of Illness Time Adapted from Murray SA et al. BMJ 2008 Predictable transition point or prognosis Short period of evident decline

Predictable transition point or prognosis

Short period of evident decline

AIDS in the HAART era The use of HAART has significantly reduced AIDS-related mortality in the developed world AIDS changed from a rapidly fatal illness into a manageable chronic disease . For many patients , HAART has meant the possibility of full return of function and health For some patients , treatment has meant the emergence of a chronic disease phase characterized by exacerbations, remissions, and eventual decline and death from the illness The impact of HAART on the natural history of AIDS has resulted in a much more variable trajectory of illness .

The use of HAART has significantly reduced AIDS-related mortality in the developed world

AIDS changed from a rapidly fatal illness into a manageable chronic disease .

For many patients , HAART has meant the possibility of full return of function and health

For some patients , treatment has meant the emergence of a chronic disease phase characterized by exacerbations, remissions, and eventual decline and death from the illness

The impact of HAART on the natural history of AIDS has resulted in a much more variable trajectory of illness .

Trajectory of AIDS decline in the HAART era Death Severity of Illness Time Adapted from Murray SA et al. BMJ 2008 Unpredictable course with more prognostic uncertainty Gradual decline

Unpredictable course with more prognostic uncertainty

Gradual decline

In the pre-HAART era, AIDS opportunistic infections (OI) were the most common cause of death. Following the introduction of HAART there was an increasing proportion of deaths due to co-morbidities such as chronic hepatitis B and C and concomitant malignancies (both AIDS- and non-AIDS defining), in addition to antiretroviral treatment failure and HAART-related toxicities. In the HAART era many HIV providers have not had much experience in the issues surrounding death and dying. HIV physicians (France, 2002) were more prone to consider that palliative care should be used only for terminally-ill patients, and only after all curative treatments have failed. Mocroft A, AIDS 2002. Bonnet F, HIV Med 2002. CASCADE Collaboration, AIDS 2006. Sabin CA, AIDS 2006. Lewden C, JAIDS 2008. Peretti-Watell P, AIDS Care 2004. Introduction

In the pre-HAART era, AIDS opportunistic infections (OI) were the most common cause of death.

Following the introduction of HAART there was an increasing proportion of deaths due to co-morbidities such as chronic hepatitis B and C and concomitant malignancies (both AIDS- and non-AIDS defining), in addition to antiretroviral treatment failure and HAART-related toxicities.

In the HAART era many HIV providers have not had much experience in the issues surrounding death and dying.

HIV physicians (France, 2002) were more prone to consider that palliative care should be used only for terminally-ill patients, and only after all curative treatments have failed.

Objectives To describe mortality trends and causes of death among HIV-infected patients in the HAART era. To explore perceptions and attitudes of INMI Infectious Diseases Physicians toward palliative care for AIDS disease

To describe mortality trends and causes of death among HIV-infected patients in the HAART era.

To explore perceptions and attitudes of INMI Infectious Diseases Physicians toward palliative care for AIDS disease

Methods Deaths were reviewed that occurred among 664 HIV-infected patients hospitalized at the National Institute for Infectious Diseases “L. Spallanzani” ( INMI ), Rome between January 1999 and December 2007 . Causes of death were grouped into 7 categories. AIDS-related categories : AIDS-related malignancy, AIDS opportunistic infections). N on-AIDS-related causes : hepatitis/liver-related, other [non-opportunistic] infections, non-AIDS-related malignancy. O ther/unknown . When more than one cause of death was found, the most likely underlying cause was scored independently by a panel of three physicians until a final consensus was reached. Written questionnaire to 45 INMI Infectious Diseases Physicians in September 2008. 7 closed questions.

Deaths were reviewed that occurred among 664 HIV-infected patients hospitalized at the National Institute for Infectious Diseases “L. Spallanzani” ( INMI ), Rome between January 1999 and December 2007 .

Causes of death were grouped into 7 categories. AIDS-related categories : AIDS-related malignancy, AIDS opportunistic infections). N on-AIDS-related causes : hepatitis/liver-related, other [non-opportunistic] infections, non-AIDS-related malignancy. O ther/unknown .

When more than one cause of death was found, the most likely underlying cause was scored independently by a panel of three physicians until a final consensus was reached.

Written questionnaire to 45 INMI Infectious Diseases Physicians in September 2008. 7 closed questions.

HIV/AIDS in 1999-2007 period INMI HIV-infected patients: 13.680 (43.8%) hospital admissions; in-hospital mortality rate 4.8% 4307 AIDS deaths reported in Italy 1116 AIDS deaths reported in Lazio Region 485 AIDS deaths reported in INMI ( 43.4% out of Lazio Region and 11.3% out of Italy ) Source SIO INMI – COA ISS

INMI HIV-infected patients: 13.680 (43.8%) hospital admissions; in-hospital mortality rate 4.8%

4307 AIDS deaths reported in Italy

1116 AIDS deaths reported in Lazio Region

485 AIDS deaths reported in INMI ( 43.4% out of Lazio Region and 11.3% out of Italy )

Patients’ characteristics at death All no. 664 1999-2001 no. 229 2002-2004 no. 244 2005-2007 no. 191 Median age (range), years 42.9 (19-86) 40.4 (19-74) 43.4 (21-80) 44.7 (20-86) Male sex (%) 521 (78.5) 181 (79) 189 (77.5) 151 (79.1) Foreign born (%) 62 (9.3) 11 (4.8) 31 (12.7) 20 (10.5) AIDS-defining illness (%) 485 (73) 175 (76.4) 186 (76.2) 124 (64.9)

Causes of death by category, INMI 1999-2007 no. 229 no. 191 no. 244 %

AIDS/non-AIDS-related causes of death (COD), INMI 1999-2007 no. 229 no. 244 no. 191 %

In summary At our Institute, in-hospital mortality rate among HIV-infected patients declined from 5.1% in 1999-2001 to 4.4% in 2005-2007. The proportion of deaths related to a non-AIDS-defining event increase d from 1999-2001 to 2005-2007 (42% to 51%). The proportion of liver-related deaths increased from 1999-2001 to 2005-2007 (15.7% to 27.2%) The proportion of deaths related to non-AIDS defining malignancies increased from 6.6% in 1999-2001 to 8.9% in 2005-2007. Liver-related vs AIDS-defining ( opportunistic infections and malignancies) 2005-2007 deaths showed a higher mean CD4 lymphocyte count/mm 3 (207 vs 82 ; p = .001) and a lower mean HIV RNA copies/ml (3.19 log 10 vs 4.12 log 10 ; p = .041)

At our Institute, in-hospital mortality rate among HIV-infected patients declined from 5.1% in 1999-2001 to 4.4% in 2005-2007.

The proportion of deaths related to a non-AIDS-defining event increase d from 1999-2001 to 2005-2007 (42% to 51%).

The proportion of liver-related deaths increased from 1999-2001 to 2005-2007 (15.7% to 27.2%)

The proportion of deaths related to non-AIDS defining malignancies increased from 6.6% in 1999-2001 to 8.9% in 2005-2007.

Liver-related vs AIDS-defining ( opportunistic infections and malignancies) 2005-2007 deaths showed a higher mean CD4 lymphocyte count/mm 3 (207 vs 82 ; p = .001) and a lower mean HIV RNA copies/ml (3.19 log 10 vs 4.12 log 10 ; p = .041)

P erceptions and attitudes of INMI Infectious Diseases Physicians towards palliative care for AIDS illness

Infectious Diseases Physicians opinions towards palliative care at INMI 40 questionnaires (89%) have been returned. Results: Identical meaning of terminal stage and end-of-life stage of AIDS illness (36%) Need for palliative care only in terminal stage , not in each stage of AIDS illness (53%) Not complete awareness of proportion of deaths due to AIDS at INMI (73%) Difficulties to communicate prognosis of end-of-life associated with the decision to do not refer AIDS patients to Hospice (53%)

40 questionnaires (89%) have been returned.

Results:

Identical meaning of terminal stage and end-of-life stage of AIDS illness (36%)

Need for palliative care only in terminal stage , not in each stage of AIDS illness (53%)

Not complete awareness of proportion of deaths due to AIDS at INMI (73%)

Difficulties to communicate prognosis of end-of-life associated with the decision to do not refer AIDS patients to Hospice (53%)

Conclusions In the HAART era, AIDS is a chronic, progressive disease that may be effectively managed in many patients but it is still associated to a significant mortality. Death rates from non-AIDS-related conditions , particularly hepatic failure and malignancy, may continue to rise in future years as HIV-patients survive for longer . Patients with HIV/AIDS have palliative care needs at each stage of the illness , as side effects of HAART and different symptoms arise. Many symptoms throughout the disease impact quality of life. In this context, need for palliative care will become more important in HIV/AIDS , and both palliative and curative approaches should be more considered throughout the course of HIV/AIDS disease in the HAART era.

In the HAART era, AIDS is a chronic, progressive disease that may be effectively managed in many patients but it is still associated to a significant mortality.

Death rates from non-AIDS-related conditions , particularly hepatic failure and malignancy, may continue to rise in future years as HIV-patients survive for longer .

Patients with HIV/AIDS have palliative care needs at each stage of the illness , as side effects of HAART and different symptoms arise. Many symptoms throughout the disease impact quality of life.

In this context, need for palliative care will become more important in HIV/AIDS , and both palliative and curative approaches should be more considered throughout the course of HIV/AIDS disease in the HAART era.

Conclusions Majority of Infectious Diseases Physicians focus of care on HAART and not on palliative care , also when HAART is not effective or patients have co-morbidities or other fatal complications. Infectious Diseases Physicians should be more informed about the utility of providing palliative care , even for patients who are not in end-of-life stage of AIDS illness and should improve their communication skills as an essential component of end-of-life care.

Majority of Infectious Diseases Physicians focus of care on HAART and not on palliative care , also when HAART is not effective or patients have co-morbidities or other fatal complications.

Infectious Diseases Physicians should be more informed about the utility of providing palliative care , even for patients who are not in end-of-life stage of AIDS illness and should improve their communication skills as an essential component of end-of-life care.

Thanks for your attention National Institute for Infectious Disesases “L. Spallanzani”, Rome : A. Antinori, E. Girardi, F. Iacomi, G. Nurra, R. Licordari, A. Petrecchia, V. Puro, S. Rosati, A. Pellegrino and Hospice Team. Centro Operativo AIDS – ISS, Rome : P. Pezzotti Hospice INMI Acknowledgments:

National Institute for Infectious Disesases “L. Spallanzani”, Rome : A. Antinori, E. Girardi, F. Iacomi, G. Nurra, R. Licordari, A. Petrecchia, V. Puro, S. Rosati, A. Pellegrino and Hospice Team.

Centro Operativo AIDS – ISS, Rome : P. Pezzotti