Effect of Medication Adherence on Survival of HIV-Infected Adults Who Start Highly Active Antiretroviral Therapy When the CD4⁺ Cell Count Is 0.200 to 0.350 x 10⁹ cells/L

18 November 2003 | Volume 139 Issue 10 | Pages 810-816

Background: The safety of delaying highly active antiretroviral therapy (HAART) in HIV-infected patients is uncertain when the CD4⁺ cell count declines below 0.350 x 10⁹ cells/L.

Objective: To evaluate the effect of baseline CD4⁺ cell count and adherence to HAART on survival rates.

Design: Prospective observational study.

Setting: Province-wide Canadian HIV/AIDS treatment program.

Patients: 1422 HIV-infected persons initiating HAART between 1 August 1996 and 31 July 2000 and followed through 31 March 2002.

Measurements: Patients were stratified by baseline CD4⁺ cell count and adherence level. Cumulative mortality rates were evaluated by using Kaplan–Meier methods and Cox regression–estimated adjusted relative hazards.

Results: Kaplan–Meier analyses showed no survival benefit of starting HAART at a CD4⁺ count of 0.200 x 10⁹ cells/L or greater among adherent patients. Adjusted analysis showed that compared with adherent patients who initiated HAART at a CD4⁺ cell count of 0.350 x 10⁹ cells/L or greater, nonadherent patients who initiated HAART when the CD4⁺ cell count was 0.200 to 0.349 x 10⁹ cells/L had statistically elevated mortality rates (adjusted relative hazard, 2.56 [95% CI, 1.36 to 4.84]; P = 0.004). However, compared with adherent patients who initiated HAART at a CD4⁺ cell count of 0.350 x 10⁹ cells/L or greater, adherent patients who initiated HAART when the CD4⁺ cell count was 0.200 to 0.349 x 10⁹ cells/L had statistically similar mortality rates (adjusted relative hazard, 0.82 [CI, 0.45 to 1.49]; P > 0.2).

Conclusions: Delaying HAART until the CD4⁺ cell count falls to 0.200 x 10⁹ cells/L does not increase the mortality rate in HIV-infected patients with good medication adherence. Mortality rates increase if HAART is initiated below 0.200 x 10⁹ cells/L. Also, nonadherent patients have higher mortality rates than adherent patients with similar CD4⁺ cell counts. Above a CD4⁺ cell count of 0.200 x 10⁹ cells/L, medication adherence is the critical determinant of survival, not the CD4⁺ cell count at which HAART is begun.

Editors' Notes Context Highly active antiretroviral therapy (HAART) improves outcomes in HIV-infected patients. When is the best time to start this therapy? Contribution 1422 HIV-infected adults were followed for 2 to 6 years after starting HAART. Adherent patients who started treatment with lower (0.200 to 0.349 x 109 cells/L) and higher ( 0.350 x 109 cells/L) CD4+ cell counts had statistically similar mortality rates. Nonadherent patients had higher mortality rates than adherent patients, regardless of baseline CD4+ cell count of 0.200 to 0.349 x 109 cells/L or 0.350 x 109 cells/L or greater. Implications In HIV-infected patients, adherence, rather than when therapy is initiated before a CD4+ cell count of 0.200 x 109 cells/L, may be the most important determinant of survival. –The Editors

 

Author and Article Information

From St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.

Acknowledgments: The authors thank Bonnie Devlin, Elizabeth Ferris, Nada Gataric, Kelly Hsu, Myrna Reginaldo, Chandra Lips, and Peter Vann for their research and administrative assistance and Kathy Li, Kevin Craib, and Martin Schechter for their advice on the statistical methods.

Grant Support: Evan Wood is supported by the Michael Smith Foundation for Health Research. Robert Hogg is supported by the Michael Smith Foundation for Health Research through a Career Investigator Award and by Canadian Institutes of Health Research through an Investigator Award.

Potential Financial Conflicts of Interest:Honoraria: R.S. Hogg (AIDS Research Program, St. Paul's Hospital); Grants received: J.S.G. Montaner (Abbott Laboratories, Agouron Pharmaceuticals, Shire Biochem, Boehringer Ingelheim Pharmaceuticals, Belgium International GmbH, Bristol-Myers Squibb, DuPont Pharma, Gilead Sciences, Glaxo Wellcome, Hoffman-LaRoche, Kucera Pharmaceutical Co., Merck Frosst Laboratories, Pharmacia & Upjohn, Trimeris); Patents received: J.S.G. Montaner (PCT/EP 02/.05151: Co-inventor, along with Boehringer Ingelheim International GmbH, of "Use of nevirapine to treat or prevent lipid abnormalities in patients with HIV that is resistant to nevirapine"); Patents pending: J.S.G. Montaner (PCT/CA02/00796: "Pharmacological applications of mitochondrial DNA assays," filed 29 May 2002; U.S. patent application for "Pharmacological applications of mitochondrial DNA analysis," filed 29 May 2002; U.S. provincial application for "Sepsis").

Requests for Single Reprints: Julio S.G. Montaner, MD, FRCPC, AIDS Research Program, University of British Columbia/St. Paul's Hospital, 667-1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada; e-mail, jmontaner{at}hivnet.ubc.ca.

Current Author Addresses: Drs. Wood, Hogg, Harrigan, O'Shaughnessy, and Montaner and Ms. Yip: University of British Columbia/St. Paul's Hospital, 667-1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada.

Author Contributions: Conception and design: E. Wood, R.S. Hogg, B. Yip, J.S.G. Montaner.

Analysis and interpretation of the data: E. Wood, R.S. Hogg, B. Yip, J.S.G. Montaner.

Drafting of the article: E. Wood, R.S. Hogg, B. Yip, P.H. Harrigan, J.S.G. Montaner.

Critical revision of the article for important intellectual content: E. Wood, R.S. Hogg, B. Yip, P.H. Harrigan, M.V. O'Shaughnessy, J.S.G. Montaner.

Final approval of the article: E. Wood, R.S. Hogg, M.V. O'Shaughnessy, J.S.G. Montaner.

Statistical expertise: E. Wood, M.V. O'Shaughnessy.

Obtaining of funding: R.S. Hogg, M.V. O'Shaughnessy, J.S.G. Montaner.

Administrative, technical, or logistic support: E. Wood, R.S. Hogg, B. Yip, P.H. Harrigan, M.V. O'Shaughnessy, J.S.G. Montaner.

Collection and assembly of data: B. Yip.