American Journal of Epidemiology Advance Access originally published online on May 2, 2007
American Journal of Epidemiology 2007 166(2):219-227; doi:10.1093/aje/kwm047
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ORIGINAL CONTRIBUTIONS |
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
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 Montefiore Medical Center, Bronx, NY
4 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
5 Department of Biostatistics, School of Public Health, Harvard University, Boston, MA
Correspondence to Dr. Stephen Cole, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Room E7640, Baltimore, MD 21205 (e-mail: scole{at}jhsph.edu).
Received for publication August 16, 2006. Accepted for publication January 17, 2007.
Highly active antiretroviral therapy (HAART) dramatically reduces the load of circulating human immunodeficiency virus type 1 (HIV-1) by blocking replication at multiple points in the viral life cycle, but the long-term effect of HAART on viral load remains unclear. In the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study, 918 HIV-1-infected men and women who were not using antiretroviral therapy were followed for a median of 5.8 years between 1996 and 2005. Follow-up yielded 3,629 person-years of observation, during which 286 (31%) of the participants initiated HAART. A marginal structural left-censored linear model for semiannual repeated assessments of viral load showed a 1.9 log10 decrease in viral load after HAART initiation as compared with nonuse (95% confidence interval: 1.7, 2.2), which remained stable over the course of follow-up but was stronger among men (interaction p < 0.001). This association was attenuated by 10% when the authors ignored the left-censoring of viral load measurements (which comprised 20% of measurements (1,420/7,258)) and attenuated by 57% when the authors adjusted for time-varying covariates in a standard fashion rather than using the marginal structural model. In conclusion, the clinically important protective effect of HAART on dampening viral load appears to be rapid, present at CD4 cell counts greater than 350 cells/mm3, and sustained beyond 6 years.
acquired immunodeficiency syndrome; antiretroviral therapy, highly active; bias (epidemiology); causality; confounding factors (epidemiology); HIV-1; viral load
Abbreviations: AIDS, acquired immunodeficiency syndrome; CI, confidence interval; HAART, highly active antiretroviral therapy; HIV-1, human immunodeficiency virus type 1; IPTC, inverse probability-of-treatment-and-censoring; SE, standard error
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