Diagnostic accuracy of CD4 cell count increase for virologic response after initiating highly active antiretroviral therapy

Objective:To derive and internally validate a clinical prediction rule for virologic response based on CD4 cell count increase after initiation of HAART in a resource-limited setting. Design and methods:A retrospective cohort study at two HIV care clinics in Gaborone, Botswana. The participants were previously treatment-naive HIV-1-infected individuals initiating HAART. The main outcome measure was a plasma HIV-1 RNA level (viral load) ≤ 400 copies/ml (i.e. undetectable) 6 months after initiating HAART. Results:The ability of CD4 cell count increase to predict an undetectable viral load was significantly better in those with baseline CD4 cell counts ≤ 100 cells/μl [area under the ROC curve (AUC), 0.78; 95% confidence interval (CI), 0.67–0.89; versus AUC, 0.60; 95% CI, 0.48–0.71; P = 0.018]. The sensitivity, specificity, and positive and negative predictive values of a CD4 cell count increase of ≥ 50 cells/μl for an undetectable viral load in those with baseline CD4 cell counts ≤ 100 cells/μl were 93.1, 61.3, 92.5 and 63.3%, respectively. Alternatively, these values were 47.8, 87.1, 95.0 and 24.5%, respectively, if a increase in CD4 cell count of ≥ 150 cells/μl was used. Conclusions:CD4 cell count increase after initiating HAART has only moderate discriminative ability in identifying patients with an undetectable viral load, and the predictive ability is lower in patients with lower baseline CD4 cell counts. Although HIV treatment programs in resource-constrained settings could consider the use of CD4 cell count increases to triage viral load testing, more accurate approaches to monitoring virologic failure are urgently needed.

[1]  N. Ford,et al.  Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment , 2006, The Lancet.

[2]  L. Myer,et al.  CD4 cell count recovery among HIV-infected patients with very advanced immunodeficiency commencing antiretroviral treatment in sub-Saharan Africa , 2006, BMC infectious diseases.

[3]  A. Evans,et al.  Translating Clinical Research into Clinical Practice: Impact of Using Prediction Rules To Make Decisions , 2006, Annals of Internal Medicine.

[4]  Kara Wools-Kaloustian,et al.  Viability and effectiveness of large-scale HIV treatment initiatives in sub-Saharan Africa: experience from western Kenya , 2006, AIDS.

[5]  R. Greenblatt,et al.  Genotypic Resistance and Immunologic Outcomes Among HIV-1-Infected Women With Viral Failure , 2006, Journal of acquired immune deficiency syndromes.

[6]  L. Myer,et al.  Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design , 2005, AIDS.

[7]  P. Wright,et al.  Antiretroviral therapy in a thousand patients with AIDS in Haiti. , 2005, The New England journal of medicine.

[8]  I. Thior,et al.  Initial Response to Highly Active Antiretroviral Therapy in HIV-1C-Infected Adults in a Public Sector Treatment Program in Botswana , 2005, Journal of acquired immune deficiency syndromes.

[9]  M. Egger,et al.  Response to Highly Active Antiretroviral Therapy at 6 Months and Long-Term Disease Progression in HIV-1 Infection , 2005, Journal of acquired immune deficiency syndromes.

[10]  J. Simon,et al.  Hard choices: rationing antiretroviral therapy for HIV/AIDS in Africa , 2005, The Lancet.

[11]  M. Peeters,et al.  Effectiveness and safety of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine in HIV-1-infected adults in Cameroon: open-label multicentre trial , 2004, The Lancet.

[12]  G. Maartens,et al.  Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa , 2004, AIDS.

[13]  D. Richman,et al.  Baseline Predictors of CD4 T‐Lymphocyte Recovery With Combination Antiretroviral Therapy , 2002, Journal of acquired immune deficiency syndromes.

[14]  D. Cooper,et al.  The extent of HIV-1-related immunodeficiency and age predict the long-term CD4 T lymphocyte response to potent antiretroviral therapy , 2002, AIDS.

[15]  H. Fleury,et al.  Predictors of long-term increase in CD4(+) cell counts in human immunodeficiency virus-infected patients receiving a protease inhibitor-containing antiretroviral regimen. , 2002, The Journal of infectious diseases.

[16]  F. Maggiolo,et al.  Discordant immunological response in HIV-positive patients on non-nucleoside reverse transcriptase inhibitor-based regimens. , 2002, AIDS (London).

[17]  D. Redelmeier,et al.  Prognostic indices in clinical practice. , 2001, JAMA.

[18]  J. Margolick,et al.  Immunologic and virologic response to highly active antiretroviral therapy in the Multicenter AIDS Cohort Study , 2001, AIDS.

[19]  Mardge H. Cohen,et al.  The relationship between virus load response to highly active antiretroviral therapy and change in CD4 cell counts: A report from the Women's interagency HIV study. , 2000, The Journal of infectious diseases.

[20]  B. Yip,et al.  Full suppression of viral load is needed to achieve an optimal CD4 cell count response among patients on triple drug antiretroviral therapy , 2000, AIDS.

[21]  G H Guyatt,et al.  Users' guides to the medical literature: XXII: how to use articles about clinical decision rules. Evidence-Based Medicine Working Group. , 2000, JAMA.

[22]  L. Jagodzinski,et al.  Use of Calibrated Viral Load Standards for Group M Subtypes of Human Immunodeficiency Virus Type 1 To Assess the Performance of Viral RNA Quantitation Tests , 2000, Journal of Clinical Microbiology.

[23]  M. Holodniy Viral load monitoring in HIV Infection , 1999, Current infectious disease reports.

[24]  M. Kazatchkine,et al.  Discrepant responses to triple combination antiretroviral therapy in advanced HIV disease , 1998, AIDS.

[25]  Amalio Telenti,et al.  CD4-cell count in HIV-1-infected individuals remaining viraemic with highly active antiretroviral therapy (HAART) , 1998, The Lancet.

[26]  I. Stiell,et al.  Implementation of the Ottawa Knee Rule for the use of radiography in acute knee injuries. , 1997, JAMA.

[27]  M. Hughes,et al.  Monitoring Plasma HIV-1 RNA Levels in Addition to CD4+ Lymphocyte Count Improves Assessment of Antiretroviral Therapeutic Response , 1997, Annals of Internal Medicine.

[28]  S. Hammer Advances in antiretroviral therapy and viral load monitoring. , 1996, AIDS.

[29]  B. Efron Estimating the Error Rate of a Prediction Rule: Improvement on Cross-Validation , 1983 .

[30]  C. Dolea,et al.  World Health Organization , 1949, International Organization.

[31]  C.G.A. Mcgregor Progress on Global Access to HIV Antiretroviral Therapy , 2006 .

[32]  James Curran,et al.  Scaling Up Antiretroviral Therapy in Resource-Limited Settings: Treatment Guidelines for a Public Health Approach , 2005 .

[33]  V. Stone,et al.  Primary care guidelines for the management of persons infected with human immunodeficiency virus: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.