Short-term clinical disease progression in HIV-1-positive patients taking combination antiretroviral therapy: the EuroSIDA risk-score

Objectives:To derive and validate a clinically applicable prognostic score for predicting short-term disease progression in HIV-infected patients taking combination antiretroviral therapy (cART). Design and methods:Poisson regression was used to identify prognostic markers for new AIDS/death in patients taking cART. A score was derived for 4169 patients from EuroSIDA and validated on 5150 patients from the Swiss HIV Cohort Study (SHCS). Results:In EuroSIDA, 658 events occurred during 22 321 person-years of follow-up: an incidence rate of 3.0/100 person-years of follow-up [95% confidence interval (CI), 2.7–3.3]. Current levels of viral load, CD4 cell count, CD4 cell slope, anaemia, and body mass index all independently predicted new AIDS/death, as did age, exposure group, a prior AIDS diagnosis, prior antiretroviral treatment and stopping all antiretroviral drugs. The EuroSIDA risk-score was divided into four strata; a patient in the lowest strata would have predicted chance of new AIDS/death of 1 in 801, 1 in 401 and 1 in 201 within the next 3, 6 or 12 months, respectively. The corresponding figures for the highest strata were 1 in 17, 1 in 9 and 1 in 5, respectively. A single-unit increase in the risk-score was associated with a 2.70 times higher incidence of clinical progression (95% CI, 2.56–2.84) in EuroSIDA and 2.88 (95% CI, 2.75–3.02) in SHCS. Conclusions:A clinically relevant prognostic score was derived in EuroSIDA and validated within the SHCS, with good agreement. The EuroSIDA risk-score will be made available publicly via an interface that will perform all calculations for the individual.

[1]  A. Mocroft,et al.  Interruption of combination antiretroviral therapy and risk of clinical disease progression to AIDS or death , 2007, HIV medicine.

[2]  J Darbyshire,et al.  CD4+ count-guided interruption of antiretroviral treatment. , 2006, The New England journal of medicine.

[3]  A. Mocroft,et al.  The feasibility of clinical endpoint trials in HIV infection in the highly active antiretroviral treatment (HAART) era , 2006, Clinical trials.

[4]  J. Gatell,et al.  Changes over time in risk of initial virological failure of combination antiretroviral therapy: a multicohort analysis, 1996 to 2002. , 2006, Archives of internal medicine.

[5]  A. Mocroft,et al.  Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. , 2005, The Journal of infectious diseases.

[6]  M. Moroni,et al.  Interruption of Highly Active Antiretroviral Therapy in HIV Clinical Practice: Results From the Italian Cohort of Antiretroviral-Naive Patients , 2005, Journal of acquired immune deficiency syndromes.

[7]  A. Mocroft,et al.  Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort , 2005, AIDS.

[8]  F. Goebel Immune Reconstitution Inflammatory Syndrome (IRIS)—Another New Disease Entity Following Treatment Initiation of HIV Infection , 2005, Infection.

[9]  A. Mocroft,et al.  Causes of death in HIV infection: the key determinant to define the clinical response to anti-HIV therapy , 2004, AIDS.

[10]  B. Ledergerber,et al.  HIV Cohort Collaborations: Proposal for Harmonization of Data Exchange , 2004, Antiviral therapy.

[11]  Christopher D Pilcher,et al.  Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. , 2004, The New England journal of medicine.

[12]  R. Greenblatt,et al.  Total Lymphocyte Count, Hemoglobin, and Delayed-Type Hypersensitivity as Predictors of Death and AIDS Illness in HIV-1–Infected Women Receiving Highly Active Antiretroviral Therapy , 2004, Journal of acquired immune deficiency syndromes.

[13]  Mardge H. Cohen,et al.  The Prognostic Importance of Changes in CD4+ Cell Count and HIV-1 RNA Level in Women after Initiating Highly Active Antiretroviral Therapy , 2004, Annals of Internal Medicine.

[14]  A. Mocroft,et al.  Decline in the AIDS and death rates in the EuroSIDA study: an observational study , 2003, The Lancet.

[15]  A. Phillips,et al.  Short-term risk of AIDS according to current CD4 cell count and viral load in antiretroviral drug-naive individuals and those treated in the monotherapy era , 2003, AIDS.

[16]  Jonathan AC Sterne,et al.  Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies , 2002, The Lancet.

[17]  Victor DeGruttola,et al.  Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial. , 2002, JAMA.

[18]  A. Mocroft,et al.  A clinically prognostic scoring system for patients receiving highly active antiretroviral therapy: results from the EuroSIDA study. , 2002, The Journal of infectious diseases.

[19]  Julio S. G. Montaner,et al.  Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy. , 2001, JAMA.

[20]  Richard D Moore,et al.  HIV-1 RNA, CD4 T-lymphocytes, and clinical response to highly active antiretroviral therapy , 2001, AIDS.

[21]  M. Battegay,et al.  Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study , 2000, The Lancet.

[22]  P. Francioli,et al.  Clinical epidemiology and research on HIV infection in Switzerland: the Swiss HIV Cohort Study 1988-2000. , 2000, Schweizerische medizinische Wochenschrift.

[23]  M. Kazatchkine,et al.  Clinical Outcome of Patients with HIV-1 Infection according to Immunologic and Virologic Response after 6 Months of Highly Active Antiretroviral Therapy , 2000, Annals of Internal Medicine.

[24]  A. Mocroft,et al.  Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe. EuroSIDA study group. , 1999, AIDS.

[25]  K. Covinsky,et al.  Assessing the Generalizability of Prognostic Information , 1999, Annals of Internal Medicine.

[26]  A. Telenti,et al.  Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study , 1999, The Lancet.

[27]  J. Castilla,et al.  Patterns of response (CD4 cell count and viral load) at 6 months in HIV-infected patients on highly active antiretroviral therapy. , 1999, AIDS.

[28]  JD Lundgren,et al.  Changing patterns of mortality across Europe in patients infected with HIV-1 , 1998, The Lancet.

[29]  C. Sabin,et al.  The rate of CD4 decline as a determinant of progression to AIDS independent of the most recent CD4 count , 1998, Epidemiology and Infection.

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

[31]  C. Gibert,et al.  Weight loss as a predictor of survival and disease progression in HIV infection. Terry Beirn Community Programs for Clinical Research on AIDS. , 1998, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[32]  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.

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

[34]  S J Pocock,et al.  Long‐term survival in patients with advanced immunodeficiency , 1997, AIDS.

[35]  B. Thiers,et al.  CD4+ Count–Guided Interruption of Antiretroviral Treatment , 2007 .

[36]  J. Bartlett The prognostic importance of changes in CD4+ cell count and HIV-1 RNA level in women after initiating highly active antiretroviral therapy , 2004 .

[37]  A. Telenti,et al.  Heterogeneity in the Response to Antiretroviral Therapy , 2001 .