Jean B. Nachega, MD, MPH; Michael Hislop, MSc; David W. Dowdy, ScM; Richard E. Chaisson, MD; Leon Regensberg, MBChB; Gary Maartens, MBChB
Note: This paper was given in part as an oral presentation at the 13th Conference on Retroviruses and Opportunistic Infections, Denver, Colorado, 5–8 February 2006 (MonOrAb#62).
Acknowledgments: The authors thank Steven G. Deeks, MD, PhD; Marc Mendelson, MD, PhD; and Mark Van Natta, MHS, for critical reading of the manuscript. They also thank Joanna Downer, PhD, and Rod Graham, MA, for technical and administrative support.
Grant Support: Drs. Nachega, Chaisson, and Maartens received support from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (R01 AI 5535901 and R01 AI 016137). Dr. Nachega is the recipient of a National Institute of Allergy and Infectious Diseases, National Institutes of Health, Mentored Patient-Oriented Research Career Award (K23 AI068582-01). Mr. Dowdy is supported by the National Institutes of Health Medical Scientist Training Program Award (5 T32 GMO7309).
Potential Financial Conflicts of Interest: Consultancies: R.E. Chaisson (Bristol-Myers Squibb); Honoraria: J.B. Nachega (GlaxoSmithKline, Merck-Sharp-Dohme for continuing medical education lectures), G. Maartens (Merck-Sharp-Dohme); Grants received: G. Maartens (Merck-Sharp-Dohme); Other: J.B. Nachega (Aspen Pharmaceuticals for conferences and travel grants).
Requests for Single Reprints: Jean B. Nachega, MD, MPH, Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Suite W5031, Baltimore, MD 21205; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Nachega: Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Suite W5031, Baltimore, MD 21205.
Mr. Hislop and Dr. Regensberg: Aid for AIDS Disease Management Programme (Pty) Ltd., PO Box 38597, Howard Place, 7450 Cape Town, South Africa.
Mr. Dowdy: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205.
Dr. Chaisson: Johns Hopkins School of Medicine, 1550 Orleans Street, Baltimore, MD 21231.
Dr. Maartens: Department of Medicine, Division of Clinical Pharmacology, University of Cape Town, Groote Schuur Hospital, K45 Old Main Building, Observatory, 7925 Cape Town, South Africa.
Author Contributions: Conception and design: J.B. Nachega, M. Hislop, R.E. Chaisson, L. Regensberg, G. Maartens.
Analysis and interpretation of the data: J.B. Nachega, M. Hislop, L. Regensberg, D.W. Dowdy, R.E. Chaisson.
Drafting of the article: J.B. Nachega, M. Hislop, D.W. Dowdy, G. Maartens.
Critical revision of the article for important intellectual content: J.B. Nachega, D.W. Dowdy, R.E. Chaisson, G. Maartens.
Final approval of the article: J.B. Nachega, D.W. Dowdy, R.E. Chaisson, L. Regensberg, G. Maartens.
Provision of study materials or patients: M. Hislop, L. Regensberg.
Statistical expertise: J.B. Nachega, D.W. Dowdy.
Administrative, technical, or logistic support: R.E. Chaisson, L. Regensberg.
Adherence of 95% or more to unboosted protease regimens is required for optimal virologic suppression in HIV-1–infected patients. Whether the same is true for nonnucleoside reverse transcriptase inhibitor (NNRTI)–based therapy is unclear.
To assess the relationship between adherence to NNRTI–based therapy and viral load in treatment-naive patients.
Observational cohort study.
Private-sector HIV and AIDS disease management program in South Africa.
2821 adults infected with HIV who began NNRTI–based therapy between January 1998 and March 2003 (2764 patients [98%] were enrolled after December 2000).
Adherence was assessed by monthly pharmacy claims. The primary end point was sustained viral load suppression (<400 copies/mL) in 100% of recorded viral load measurements throughout follow-up. Secondary end points included time to initial viral load suppression and time to subsequent virologic failure (>400 copies/mL).
The median follow-up period was 2.2 years (interquartile range, 1.7 to 2.7 years). The proportion of patients with sustained viral load suppression ranged from 13% (41 of 325 patients) in patients who filled less than 50% of antiretroviral drug prescriptions to 73% (725 of 997 patients) in those who filled 100% of antiretroviral drug prescriptions. Each 10% increase in pharmacy claim adherence greater than 50% was associated with a mean absolute increase of 0.10 in the proportion of patients with sustained virologic suppression (P < 0.001). Predictors for shorter time to virologic failure after initial suppression in multivariable Cox regression included CD4+ T-cell counts of 0.50 × 109 cells/L or less (hazard ratio, 1.60 [95% CI, 1.22 to 2.10] vs. CD4+ T-cell counts >0.20 × 109 cells/L), baseline viral load greater than 105 copies/mL (hazard ratio, 1.39 [CI, 1.14 to 1.70]), nevirapine-based regimen (hazard ratio, 1.43 [CI, 1.16 to 1.75]), and low pharmacy claim adherence (hazard ratio, 1.58 [CI, 1.48 to 1.69], per 10% decrease in adherence to 50%).
Observational study with adherence stratification at study end and lack of standardized timing for outcome measurement.
Virologic outcomes improve in a linear dose–response manner as adherence to NNRTI–based regimens increases beyond 50%.
Nachega JB, Hislop M, Dowdy DW, et al. Adherence to Nonnucleoside Reverse Transcriptase Inhibitor–Based HIV Therapy and Virologic Outcomes. Ann Intern Med. 2007;146:564–573. doi: 10.7326/0003-4819-146-8-200704170-00007
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Published: Ann Intern Med. 2007;146(8):564-573.
HIV, Infectious Disease.
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