Am J Epidemiol 2003; 158:687-694.
Copyright © 2003 by Johns
Hopkins Bloomberg School of Public Health
ORIGINAL CONTRIBUTIONS |
Effect of Highly Active Antiretroviral Therapy on Time to Acquired Immunodeficiency Syndrome or Death using Marginal Structural Models
1 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
2 Department of Epidemiology, School of Public Health, Harvard University, Boston, MA.
3 Department of Biostatistics, School of Public Health, Harvard University, Boston, MA.
4 Lincoln Medical and Mental Health Center, New York, NY.
5 Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
6 Department of Epidemiology, School of Public Health, University of California, Los Angeles, Los Angeles, CA.
7 Kenneth Norris Jr. Cancer Hospital, Los Angeles, CA.
8 Department of Preventive Medicine and Community Health, Health Science Center at Brooklyn, State University of New York, Brooklyn, Brooklyn, NY.
9 Departments of Medicine and Epidemiology, University of California, San Francisco, San Francisco, CA.
10 Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
11 Division of Infectious Diseases, Georgetown University Hospital, Washington, DC.
12 Cook County Hospital, Chicago, IL.
To estimate the net (i.e., overall) effect of highly active antiretroviral therapy (HAART) on time to acquired immunodeficiency syndrome (AIDS) or death, the authors used inverse probability-of-treatment weighted estimation of a marginal structural model, which can appropriately adjust for time-varying confounders affected by prior treatment or exposure. Human immunodeficiency virus (HIV)-positive men and women (n = 1,498) were followed in two ongoing cohort studies between 1995 and 2002. Sixty-one percent (n = 918) of the participants initiated HAART during 6,763 person-years of follow-up, and 382 developed AIDS or died. Strong confounding by indication for HAART was apparent; the unadjusted hazard ratio for AIDS or death was 0.98. The hazard ratio from a standard time-dependent Cox model that included time-varying CD4 cell count, HIV RNA level, and other time-varying and fixed covariates as regressors was 0.81 (95% confidence interval: 0.61, 1.07). In contrast, the hazard ratio from a marginal structural survival model was 0.54 (robust 95% confidence interval: 0.38, 0.78), suggesting a clinically meaningful net benefit of HAART. Standard Cox analysis failed to detect a clear net benefit, because it does not appropriately adjust for time-dependent covariates, such as HIV RNA level and CD4 cell count, that are simultaneously confounders and intermediate variables.
acquired immunodeficiency syndrome; antiretroviral therapy, highly active; causality; confounding factors (epidemiology)
Abbreviations: Abbreviations: AIDS, acquired immunodeficiency syndrome; CI, confidence interval; HAART, highly active antiretroviral therapy; HIV, human immunodeficiency virus; HR, hazard ratio; NRTI, nucleoside reverse transcriptase inhibitor; PCP, Pneumocystis carinii pneumonia.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Argyropoulos, C.-C. H. Chang, L. Plantinga, N. Fink, N. Powe, and M. Unruh Considerations in the Statistical Analysis of Hemodialysis Patient Survival J. Am. Soc. Nephrol., September 1, 2009; 20(9): 2034 - 2043. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Walensky, L. L. Wolf, R. Wood, M. O. Fofana, K. A. Freedberg, N. A. Martinson, A. D. Paltiel, X. Anglaret, M. C. Weinstein, E. Losina, et al. When to Start Antiretroviral Therapy in Resource-Limited Settings Ann Intern Med, August 4, 2009; 151(3): 157 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Palella Jr., C. Armon, K. Buchacz, S. R. Cole, J. S. Chmiel, R. M. Novak, K. Wood, A. C. Moorman, J. T. Brooks, and for the HOPS (HIV Outpatient Study) Investigators The Association of HIV Susceptibility Testing With Survival Among HIV-Infected Patients Receiving Antiretroviral Therapy: A Cohort Study Ann Intern Med, July 21, 2009; 151(2): 73 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. E. Cain, S. R. Cole, S. Greenland, T. T. Brown, J. S. Chmiel, L. Kingsley, and R. Detels Effect of Highly Active Antiretroviral Therapy on Incident AIDS Using Calendar Period as an Instrumental Variable Am. J. Epidemiol., May 1, 2009; 169(9): 1124 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. THAMER, M. A. HERNAN, Y. ZHANG, D. COTTER, and M. PETRI Prednisone, Lupus Activity, and Permanent Organ Damage J Rheumatol, March 1, 2009; 36(3): 560 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A Hernan, M. McAdams, N. McGrath, E. Lanoy, and D. Costagliola Observation plans in longitudinal studies with time-varying treatments Statistical Methods in Medical Research, February 1, 2009; 18(1): 27 - 52. [PDF]
|
|
|
|
|
|
S. R. Cole and M. A. Hernan Constructing Inverse Probability Weights for Marginal Structural Models Am. J. Epidemiol., September 15, 2008; 168(6): 656 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ishani, C. A. Solid, E. D. Weinhandl, D. T. Gilbertson, R. N. Foley, and A. J. Collins Association between number of months below K/DOQI haemoglobin target and risk of hospitalization and death Nephrol. Dial. Transplant., May 1, 2008; 23(5): 1682 - 1689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Fairall, M. O. Bachmann, G. M. C. Louwagie, C. van Vuuren, P. Chikobvu, D. Steyn, G. H. Staniland, V. Timmerman, M. Msimanga, C. J. Seebregts, et al. Effectiveness of Antiretroviral Treatment in a South African Program: A Cohort Study Arch Intern Med, January 14, 2008; 168(1): 86 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Cole, M. A. Hernan, K. Anastos, B. D. Jamieson, and J. M. Robins Determining the Effect of Highly Active Antiretroviral Therapy on Changes in Human Immunodeficiency Virus Type 1 RNA Viral Load using a Marginal Structural Left-censored Mean Model Am. J. Epidemiol., July 15, 2007; 166(2): 219 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H Lopez-Gatell, S. Cole, N. Hessol, A. French, R. Greenblatt, S Landesman, S Preston-Martin, and K Anastos Effect of Tuberculosis on the Survival of Women Infected with Human Immunodeficiency Virus Am. J. Epidemiol., May 15, 2007; 165(10): 1134 - 1142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Goldie, Y. Yazdanpanah, E. Losina, M. C. Weinstein, X. Anglaret, R. P. Walensky, H. E. Hsu, A. Kimmel, C. Holmes, J. E. Kaplan, et al. Cost-Effectiveness of HIV Treatment in Resource-Poor Settings -- The Case of Cote d'Ivoire N. Engl. J. Med., September 14, 2006; 355(11): 1141 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Nuesch, P. Srasuebkul, J. Ananworanich, K. Ruxrungtham, P. Phanuphak, C. Duncombe, and on behalf of the HIV-NAT Study Team Monitoring the toxicity of antiretroviral therapy in resource limited settings: a prospective clinical trial cohort in Thailand J. Antimicrob. Chemother., September 1, 2006; 58(3): 637 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A Hernan and J. M Robins Estimating causal effects from epidemiological data. J Epidemiol Community Health, July 1, 2006; 60(7): 578 - 586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Burke-Miller, J. A. Cook, M. H. Cohen, N. A. Hessol, T. E. Wilson, J. L. Richardson, P. Williams, and S. J. Gange Longitudinal Relationships Between Use of Highly Active Antiretroviral Therapy and Satisfaction With Care Among Women Living With HIV/AIDS Am J Public Health, June 1, 2006; 96(6): 1044 - 1051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Hernan Invited Commentary: Hypothetical Interventions to Define Causal Effects--Afterthought or Prerequisite? Am. J. Epidemiol., October 1, 2005; 162(7): 618 - 620. [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Bacon, V. von Wyl, C. Alden, G. Sharp, E. Robison, N. Hessol, S. Gange, Y. Barranday, S. Holman, K. Weber, et al. The Women's Interagency HIV Study: an Observational Cohort Brings Clinical Sciences to the Bench Clin. Vaccine Immunol., September 1, 2005; 12(9): 1013 - 1019. [Full Text] [PDF]
|
|
|
|
|
|
S. R. Cole, M. A. Hernan, J. B. Margolick, M. H. Cohen, and J. M. Robins Marginal Structural Models for Estimating the Effect of Highly Active Antiretroviral Therapy Initiation on CD4 Cell Count Am. J. Epidemiol., September 1, 2005; 162(5): 471 - 478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Mortimer, R. Neugebauer, M. van der Laan, and I. B. Tager An Application of Model-Fitting Procedures for Marginal Structural Models Am. J. Epidemiol., August 15, 2005; 162(4): 382 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Teng, M. Wolf, M. N. Ofsthun, J. M. Lazarus, M. A. Hernan, C. A. Camargo Jr, and R. Thadhani Activated Injectable Vitamin D and Hemodialysis Survival: A Historical Cohort Study J. Am. Soc. Nephrol., April 1, 2005; 16(4): 1115 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lindblad, J. Lagergren, and L. A. Garcia Rodriguez Nonsteroidal Anti-inflammatory Drugs and Risk of Esophageal and Gastric Cancer Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 444 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Bodnar, M. Davidian, A. M. Siega-Riz, and A. A. Tsiatis Marginal Structural Models for Analyzing Causal Effects of Time-dependent Treatments: An Application in Perinatal Epidemiology Am. J. Epidemiol., May 15, 2004; 159(10): 926 - 934. [Abstract] [Full Text] [PDF]
|
|