Adherence to Nonnucleoside Reverse Transcriptase Inhibitor–Based HIV Therapy and Virologic Outcomes

17 April 2007 | Volume 146 Issue 8 | Pages 564-573

Background: 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.

Objective: To assess the relationship between adherence to NNRTI–based therapy and viral load in treatment-naive patients.

Design: Observational cohort study.

Setting: Private-sector HIV and AIDS disease management program in South Africa.

Patients: 2821 adults infected with HIV who began NNRTI–based therapy between January 1998 and March 2003 (2764 patients [98%] were enrolled after December 2000).

Measurements: 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).

Results: 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 x 10⁹ cells/L or less (hazard ratio, 1.60 [95% CI, 1.22 to 2.10] vs. CD4⁺ T-cell counts >0.20 x 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%).

Limitations: Observational study with adherence stratification at study end and lack of standardized timing for outcome measurement.

Conclusion: Virologic outcomes improve in a linear dose–response manner as adherence to NNRTI–based regimens increases beyond 50%.

Editors' Notes Context It is unclear whether HIV treatment regimens that contain nonnucleoside reverse transcriptase inhibitors (NNRTIs) require the same high level of adherence for optimal viral suppression as regimens that do not contain these agents. Contribution This study evaluated adherence and viral suppression among 2821 HIV-1–infected patients who began NNRTI–based therapy between 1998 and 2003. The proportion of patients with sustained viral load suppression was 25% for those who had 50% to 60% adherence, increasing linearly to 73% for those who had 90% to 100% adherence. Implication Although maximal adherence to NNRTI–based therapy is optimal, it often leads to sustained viral suppression at moderate levels of adherence. —The Editors

 

Author and Article Information

From Johns Hopkins Bloomberg School of Public Health and Johns Hopkins School of Medicine, Baltimore, Maryland, and Groote Schuur Hospital, University of Cape Town, and Aid for AIDS Disease Management Programme (Pty) Ltd., Cape Town, South Africa.

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, jnachega{at}jhsph.edu.

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.

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