Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy

Objective: To determine the effect of introduction of highly active antiretroviral therapy (HAART) on survival following AIDS dementia complex (ADC). Methods: Australian AIDS notification data in the period 1993–2000 were examined. In order to examine the impact of HAART, two periods of AIDS diagnoses were chosen: pre-HAART (1993–1995) and HAART (1996–2000). Median survival was based on Kaplan–Meier estimates, with examination of factors influencing survival in a Cox proportional hazards model. Results: In the period 1993–2000 in Australia, 5017 initial AIDS illnesses were diagnosed among 4351 AIDS patients. The proportion of AIDS cases with ADC increased from 5.2% in 1993–1995 to 6.8% in 1996–2000 (P = 0.029). Median survival following AIDS increased from 19.6 months for those diagnosed with AIDS in 1993–1995 to 39.6 months for those diagnosed in 1996–2000 (P < 0.0005). Median survival following ADC increased to a greater extent than that for all other AIDS illnesses, from 11.9 months in 1993–1995 to 48.2 in 1996–2000 (P < 0.0005). Most striking was the increase in survival among those with ADC and a CD4 cell count < 100 × 106 cells/l at diagnosis; 5.1 months in 1993–1995 to 38.5 months in 1996–2000 (P < 0.0005). Conclusion: Although there has been a proportional increase in ADC at AIDS diagnosis, survival following ADC has improved markedly in the era of HAART.

[1]  Andrew J. Saykin,et al.  Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus‐type 1 (HIV‐1) infection , 1991, Neurology.

[2]  H. Brodt,et al.  Changing incidence of AIDS‐defining illnesses in the era of antiretroviral combination therapy , 1997, AIDS.

[3]  P. Pezzotti,et al.  Differential Impact of Combined Antiretroviral Therapy on the Survival of Italian Patients With Specific AIDS‐Defining Illnesses , 2000, Journal of acquired immune deficiency syndromes.

[4]  S. Hammer,et al.  A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter. AIDS Clinical Trials Group Study 175 Study Team. , 1996, The New England journal of medicine.

[5]  M A Fischl,et al.  A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. , 1997, The New England journal of medicine.

[6]  J. Ward,et al.  Effects of antiretroviral therapy and opportunistic illness primary chemoprophylaxis on survival after AIDS diagnosis. Adult/Adolescent Spectrum of Disease Group. , 1999, AIDS.

[7]  G. Satten,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. , 1998, The New England journal of medicine.

[8]  J. Goedert,et al.  Survival after AIDS diagnosis in a cohort of hemophilia patients. Multicenter Hemophilia Cohort Study. , 1997, Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology.

[9]  D. Feaster,et al.  Mild cognitive impairment and risk of mortality in HIV-1 infection. , 1998, The Journal of neuropsychiatry and clinical neurosciences.

[10]  D. Costagliola,et al.  Incidence and risk factors for toxoplasmic encephalitis in human immunodeficiency virus-infected patients before and during the highly active antiretroviral therapy era. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  R. Chaisson,et al.  Natural history of HIV infection in the era of combination antiretroviral therapy. , 1999, AIDS.

[12]  D. Gertig,et al.  The acquired immunodeficiency syndrome in Australia: incidence 1982–1991 , 1993, The Medical journal of Australia.

[13]  R. Chaisson,et al.  Impact of opportunistic disease on survival in patients with HIV infection , 1998, AIDS.

[14]  I. Keet,et al.  Cerebrospinal-fluid HIV-1 RNA and drug concentrations after treatment with lamivudine plus zidovudine or stavudine , 1998, The Lancet.

[15]  R. Hogg,et al.  Improved survival among HIV-infected individuals following initiation of antiretroviral therapy. , 1998, JAMA.

[16]  M. Jacobson,et al.  Decline in the rate of specific opportunistic infections at San Francisco General Hospital, 1994-1997. , 1998, AIDS.

[17]  F. Derouin,et al.  Changing patterns of disease and treatment of opportunistic parasitic infections in patients with AIDS. , 1998, Current opinion in infectious diseases.

[18]  A. De Luca,et al.  The effect of potent antiretroviral therapy and JC virus load in cerebrospinal fluid on clinical outcome of patients with AIDS-associated progressive multifocal leukoencephalopathy. , 2000, The Journal of infectious diseases.

[19]  J. Ward,et al.  Surveillance for AIDS-defining opportunistic illnesses, 1992-1997. , 1999, MMWR. CDC surveillance summaries : Morbidity and mortality weekly report. CDC surveillance summaries.

[20]  J. Kaldor,et al.  Improving survival following AIDS in Australia, 1991–1996 , 2000, AIDS.

[21]  F. Wit,et al.  Randomised trial of addition of lamivudine or lamivudine plus loviride to zidovudine-containing regimens for patients with HIV-1 infection: the CAESAR trial , 1997 .

[22]  S. Mallal,et al.  Trends in incidence of AIDS illnesses in Australia from 1983 to 1994: the Australian AIDS cohort. , 1997, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[23]  J. Darbyshire,et al.  Delta: a randomised double-blind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals , 1996, The Lancet.

[24]  J. Kaldor,et al.  Changes to AIDS dementia complex in the era of highly active antiretroviral therapy. , 1999, AIDS.

[25]  V. Calvez,et al.  Clinical and spectroscopic improvement in HIV-associated cognitive impairment , 2001, Neurology.

[26]  M. Lederman,et al.  Neurological outcomes in late HIV infection: adverse impact of neurological impairment on survival and protective effect of antiviral therapy. AIDS Clinical Trial Group and Neurological AIDS Research Consortium study team. , 1999, AIDS.

[27]  J. Kaldor,et al.  HIV disease progression in Australia in the time of combination antiretroviral therapies , 1998, The Medical journal of Australia.

[28]  P. Pezzotti,et al.  Increasing survival time after AIDS in Italy: the role of new combination antiretroviral therapies. Tuscany AIDS Study Group. , 1999, AIDS.

[29]  O. Selnes,et al.  Variable progression of HIV‐associated dementia , 1998, Neurology.

[30]  J. McArthur,et al.  Progression of HIV-associated dementia treated with HAART. , 2002, The AIDS reader.

[31]  J. Cuzick.  A Wilcoxon-type test for trend. , 1985, Statistics in medicine.

[32]  R. Brettle,et al.  Predicting survival in AIDS: refining the model. , 1997, QJM : monthly journal of the Association of Physicians.

[33]  Jeffrey L. Jones,et al.  Progressive multifocal leukoencephalopathy: improved survival of human immunodeficiency virus-infected patients in the protease inhibitor era. , 1999, The Journal of infectious diseases.

[34]  Manuel Battegay,et al.  Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study , 1997, BMJ.

[35]  P. Kissinger,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. , 1998, The New England journal of medicine.

[36]  Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. Council of State and Territorial Epidemiologists; AIDS Program, Center for Infectious Diseases. , 1987, MMWR supplements.

[37]  G. Dore,et al.  Impact of Highly Active Antiretroviral Therapy on Individual AIDS‐Defining Illness Incidence and Survival in Australia , 2002, Journal of acquired immune deficiency syndromes.

[38]  P. Massip,et al.  Impact of protease inhibitors on AIDS‐defining events and hospitalizations in 10 French AIDS reference centres , 1997, AIDS.

[39]  I. Grant,et al.  AIDS-associated mild neurocognitive impairment is delayed in the era of highly active antiretroviral therapy. , 2001, AIDS.

[40]  F. Forastiere,et al.  Changes in survival among people with AIDS in Lazio, Italy from 1993 to 1998. Lazio AIDS Surveillance Collaborative Group. , 1999, AIDS.

[41]  Andrew Carr,et al.  HIV protease inhibitors , 1996, AIDS.