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Increases in Duration of First Highly Active Antiretroviral Therapy Over Time (1996–2009) and Associated Factors in the Multicenter AIDS Cohort Study

Slama, Laurence MD*,‖; Li, Xiuhong MAS; Brown, Todd MD, PhD; Jacobson, Lisa P. ScD, ScM; Pialoux, Gilles MD*; Macatangay, Bernard MD§; Bolan, Robert K. MD; Phair, John MD; Palella, Frank J. Jr MDfor the Multicenter AIDS cohort Study

JAIDS Journal of Acquired Immune Deficiency Syndromes: January 1st, 2014 - Volume 65 - Issue 1 - p 57–64
doi: 10.1097/QAI.0b013e3182a99a0d
Clinical Science

Background: Antiretroviral therapy (ART) regimens changes occur frequently among HIV-infected persons. Duration and type of initial highly active antiretroviral therapy (HAART) and factors associated with regimen switching were evaluated in the Multicenter AIDS Cohort Study.

Methods: Participants were classified according to the calendar period of HAART initiation: T1 (1996–2001), T2 (2002–2005), and T3 (2006–2009). Kaplan–Meier curves depicted time from HAART initiation to first regimen changes within 5.5 years. Cox proportional hazards regression models were used to examine factors associated with time to switching.

Results: Of 1009 participants, 796 changed regimen within 5.5 years after HAART initiation. The percentage of participants who switched declined from 85% during T1 to 49% in T3. The likelihood of switching in T3 decreased by 50% (P < 0.01) compared with T1 after adjustment for pre-HAART ART use, age, race, and CD4 count. Incomplete HIV suppression decreased over time (P < 0.01) but predicted switching across all time periods. Lower HAART adherence (≤95% of prescribed doses) was predictive of switching only in T1. In T2, central nervous system symptoms predicted switching [relative hazard (RH) = 1.7; P = 0.012]. Older age at HAART initiation was associated with increased switching in T1 (RH = 1.03 per year increase) and decreased switching in T2 (RH = 0.97 per year increase).

Conclusions: During the first 15 years of the HAART era, initial HAART regimen duration lengthened and regimen discontinuation rates diminished. Both HIV RNA nonsuppression and poor adherence predicted switching before 2001 while side effects that were possibly ART related were more prominent during T2.

*Tenon Hospital, Division of Infectious Diseases, Pierre and Marie Curie University, Paris, France;

Department of Epidemiology and

Division of Endocrinology and Metabolism, John Hopkins University, Baltimore, MD;

§School of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA;

L.A. Gay & Lesbian Center, Los Angeles, CA; and

Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL.

Correspondence to: Laurence Slama, MD, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, 645 N Michigan Avenue, Suite 1014, Chicago, IL 60611 (e-mail: laurence.slama@northwestern.edu).

The Multicenter AIDS cohort Study is funded by the National Institute of Allergy and Infectious Diseases. L.S. was supported by an unrestricted grant for the study from Gilead, a grant from the International AIDS Education Project Inc and by a grant from AMEVIH (not for profit foundations), a grant from Jansen, Roche, and Merck to support her visiting scholar position at Northwestern University.

T.B. is on a board membership for EMD-Serono and consults for the following commercial entities: ViiV Healthcare, Merck, Gilead, BMS, and Abbott. J.P. serves on a Data Safety and Monitoring Board for Pfizer. F.J.P. is on the speakers' bureau and consults for the following commercial entities: Gilead Sciences, Bristol Myers Squibb, Janssen Pharmaceuticals, and Merck. G.P. serves a board from the following: Abbott, BMS, Gilead, MSD, Tibotec-Janssen, and ViiV Healthcare and participated on symposium organized by Abbott, Boehringer-Ingelheim, BMS, GSK, Gilead, MSD, Pfizer, Roche, Nephrotec, Tibotec-Janssen, and ViiV Healthcare. He was also invited to national and international meeting by Abbott, BMS, Gilead, and ViiV Healthcare. The remaining authors have no conflicts of interest to disclose.

# The Multicenter AIDS Cohort Study includes the following: Baltimore: The Johns Hopkins University Bloomberg School of Public Health: J. B. Margolick (PI), B. Crain, A. Dobs, H. Farzadegan, J. Gallant, L. Johnson-Hill, M. Plankey, N. Sacktor, O. Selnes, J. Shepard, C. Thio. Chicago: Feinberg School of Medicine, Northwestern University, and Cook County Bureau of Health Services: S. M. Wolinsky (PI), J. P. Phair, S. Badri, M. O'Gorman, D. Ostrow, F. Palella, A. Ragin. Los Angeles: University of California, University of California, Los Angeles Schools of Public Health and Medicine: R. Detels (PI), O. Martínez-Maza (Co-PI), A. Aronow, R. Bolan, E. Breen, A. Butch, B. Jamieson, E. N. Miller, J. Oishi, H. Vinters, D. Wiley, M. Witt, O. Yang, S. Young, Z. Feng Zhang. Pittsburgh: University of Pittsburgh, Graduate School of Public Health: C. R. Rinaldo (PI), L. A. Kingsley (Co-PI), J. T. Becker, R. D. Cranston, J. J. Martinson, J. W. Mellors, A. J. Silvestre, R. D. Stall. Data coordinating center: The Johns Hopkins University Bloomberg School of Public Health: L. P. Jacobson (PI), A. Munoz (Co-PI), Alison, Abraham, Keri Althoff, C. Cox, G. D’Souza, E. Golub, J. Schollenberger, E. C. Seaberg, S. Su. National Institutes of Health: National Institute of Allergy and Infectious Diseases: R. E. Huebner; National Cancer Institute: Geraldina Dominguez. UO1-AI-35042, UM-AI-35043, UO1-AI-35039, UO1-AI-35040, and UO1-AI-35041. Web site located at http://www.statepi.jhsph.edu/macs/macs.html.

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Received May 20, 2013

Accepted August 04, 2013

© 2014 by Lippincott Williams & Wilkins