Clinical Prediction Guide
A simple scoring system predicted clinical progression in HIV patients receiving highly active antiretroviral therapyPDF
ACP J Club. 2002 Jul-Aug;137:37. doi:10.7326/ACPJC-2002-137-1-037
Lundgren JD, Mocroft A, Gatell JM, et al., for the EuroSIDA Study Group. A clinically prognostic scoring system for patients receiving highly active antiretroviral therapy: results from the EuroSIDA study. J Infect Dis. 2002 Jan 15;185:178-87. [PubMed ID: 11807691] (All 2002 articles were reviewed for relevancy, and abstracts were last revised in 2008.)
In patients with HIV who are receiving highly active antiretroviral therapy (HAART), does a scoring system predict clinical progression?
Prognostic scoring system developed in 1 derivation cohort and validated in 2 cohorts of patients.
60 centers in Europe and Israel.
2027 patients (median age 37 y) formed the derivation set: inception cohort of participants in the EuroSIDA study who were ≥ 16 years of age and had started a protease inhibitor or nonnucleoside reverse-transcriptase inhibitor as part of a HAART antiretroviral regimen and had CD4 cell counts and viral loads measured within 6 months before starting HAART and ≥ 1 measurement after starting HAART. 2 cohorts of patients formed the validation set: 1946 patients in the EuroSIDA study who started HAART before recruitment to the study and 1442 patients from a clinic in Barcelona who had previously started HAART.
Description of prediction guide
Cox proportional hazards models were used to determine factors associated with clinical progression. The final prediction model comprised the latest CD4 cell count, viral load, hemoglobin level, and clinical status at the start of HAART (no AIDS, severe AIDS [progressive multifocal leukoencephalopathy and non-Hodgkin lymphoma], or other AIDS diagnosis). For CD4 cell counts, the cut points were 50 and 200 cells/mm3; for viral loads, the cut points were 500 and 10000 HIV-RNA copies/mL. The normal hemoglobin level was defined as > 14 g/dL for men and 12 g/dL for women; severe anemia was defined as < 8 g/dL for men and women. Logarithms of the relative hazards were used to derive a score for the variables with independent association with the risk for clinical progression. The score ranged from 0 to 17 points.
Main outcome measure
Clinical progression (new diagnosis of an AIDS-defining event or death).
Among patients in the derivation cohort, 200 patients (9.9%) clinically progressed (death 30%, first AIDS-defining illness 47%, and new AIDS-defining illness 24%). For a 1-unit increase in score, a mean increase of 38% (95% CI 33% to 43%) occurred in risk for clinical progression. The incidence of clinical progression was 3.9/100 person-years. In the EuroSIDA and Barcelona validation cohorts, the incidence of clinical progression was 4.2 and 4.6 per 100 person years, respectively. A single point increase in score was associated with an increased risk for clinical progression of about 40% among the 3 cohorts.
In patients with HIV who are receiving highly active antiretroviral therapy, a scoring system based on the latest CD4 cell count, viral load, and hemoglobin level and a previous severe AIDS diagnosis was predictive of clinical progression. The risk for disease progression of a 1-unit increase in score was about 40%.
Sources of funding: European Commission BIOMED 1; Fifth Framework Program; GlaxoSmithKline, Roche, and Boehringer Ingelheim; Swiss Federal Office for Education and Science.
For correspondence: Dr. J.D. Lundgren, Hvidovre University Hospital, Hvidovre, Denmark. E-mail firstname.lastname@example.org.
Revised Commentary (2008)
Despite the success of HAART in reversing the immunosuppression seen in patients infected with HIV, some patients receiving HAART still have poor outcomes. To quantify the risk for a poor outcome, Lundgren and colleagues developed a point system based on CD4 T-cell numbers, viral load, hemoglobin level, and previous diagnosis of “severe” AIDS. (There is an error in the description of the scoring system at the bottom of page 181; the cutoffs for the scoring of viral load are < 500 copies/Ml, 500 to 9999 copies/Ml, and ≥ 100000 copies/Ml.) The risk for progression varied from 1/100 person-years with a score of 0, to about 11/100 person-years with a score of 6, to > 100/100 person-years with a score of ≥ 12. The strengths of this system are its simplicity, the fact that similar markers were used to predict progression before use of HAART, and the fact that intuitively the components of the prediction guide seem to be relatively important measures.
The risk score has been updated in a larger study and data set in HIV infection patients taking combination antiretroviral therapy using 4169 patient from EuroSIDA and validated in 5150 patients from the Swiss HIV Cohort Study (SHCS) (1). A single unit increase in the risk score was associated with a 2.7 times higher incidence of clinical progression (95% CI 2.56 to 2.84) in EuroSIDA and 2.88 (95% CI 2.75 to 3.03) in the SHCS.
A risk calculator that produces estimates for progression rates at 1 to 5 years after starting HAART that is based on a collaborative analysis of data from 12 cohort studies in Europe and North America on 20 379 adults, including the EuroSIDA and SHCS, is available (2). However, several recognized factors are not included in the derivation of the guide; including coinfection with hepatitis C (3), adherence (4), and baseline levels of resistance (5). I suspect, however, that most clinicians will not calculate a score but rather will continue to use the individual variables to guide decision making.
Bradley Bender, MD
Veterans Affairs Medical Center
Gainesville, Florida, USA
New References Since 2002
1. Mocroft A, Ledergerber B, Zilmer K, et al. Short-term clinical disease progression in HIV-1-positive patients taking combination antiretroviral therapy: the EuroSIDA risk score. AIDS. 2007;21:1867-75. [PubMed ID: 17721094]
2. May M, Sterne JA, Sabin C, et al. Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies. AIDS. 2007;21:1185-97. [PubMed ID: 17502729]
3. Greub G, Ledergerber B, Battegay M, 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. Lancet. 2000;356:1800-5. [PubMed ID: 11117912]
4. Mannheimer S, Friedland G, Matts J, Child C, Chesney M. The consistency of adherence to antiretroviral therapy predicts biologic outcomes for human immunodeficiency virus-infected persons in clinical trials. Clin Infect Dis. 2002;34:1115-21. [PubMed ID: 11915001]
5. Grant RM, Hecht FM, Warmerdam M, et al. Time trends in primary HIV-1 drug resistance among recently infected persons. JAMA. 2002;288:181-8. [PubMed ID: 12095382]