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Comparative Outcomes of Tenofovir-Based and Zidovudine-Based Antiretroviral Therapy Regimens in Lusaka, Zambia

Chi, Benjamin H. MD, MSc*,†; Mwango, Albert MD; Giganti, Mark J. MS*,†; Sikazwe, Izukanji MD‡,§; Moyo, Crispin MD; Schuttner, Linnaea BA*; Mulenga, Lloyd B. MD, MSc*; Bolton-Moore, Carolyn MD*,†; Chintu, Namwinga T. MD*,†; Sheneberger, Robert MD§; Stringer, Elizabeth M. MD, MSc*,†; Stringer, Jeffrey S. A. MD*,†

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15th, 2011 - Volume 58 - Issue 5 - p 475–481
doi: 10.1097/QAI.0b013e31823058a3
Epidemiology and Prevention

Background Although tenofovir (TDF) is a common component of antiretroviral therapy (ART), recent evidence suggests inferior outcomes when it is combined with nevirapine (NVP).

Methods We compared outcomes among patients initiating TDF + emtricitabine or lamivudine (XTC) + NVP, TDF + XTC + efavirenz (EFV), zidovudine (ZDV) + lamuvidine (3TC) + NVP, and ZDV + 3TC + EFV. We categorized drug exposure by initial ART dispensation by a time-varying analysis that accounted for drug substitutions and by predominant exposure (>75% of drug dispensations) during an initial window period. Risks for death and program failure were estimated using Cox proportional hazard models. All regimens were compared with ZDV + 3TC + NVP.

Results Between July 2007 and November 2010, 18,866 treatment-naive adults initiated ART: 18.2% on ZDV + 3TC + NVP, 1.8% on ZDV + 3TC + EFV, 36.2% on TDF + XTC + NVP, and 43.8% on TDF + XTC + EFV. When exposure was categorized by initial prescription, patients on TDF + XTC + NVP [adjusted hazard ratio (AHR): 1.45; 95% confidence interval (CI): 1.03 to 2.06] had a higher post–90-day mortality. TDF + XTC + NVP was also associated with an elevated risk for mortality when exposure was categorized as time-varying (AHR: 1.51; 95% CI: 1.18 to 1.95) or by predominant exposure over the first 90 days (AHR: 1.91, 95% CI: 1.09 to 3.34). However, these findings were not consistently observed across sensitivity analyses or when program failure was used as a secondary outcome.

Conclusion TDF + XTC + NVP was associated with higher mortality when compared with ZDV + 3TC + NVP but not consistently across sensitivity analyses. These findings may be explained in part by inherent limitations to our retrospective approach, including residual confounding. Further research is urgently needed to compare the effectiveness of ART regimens in use in resource-constrained settings.

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*Centre for Infectious Disease Research in Zambia, Lusaka, Zambia

Department of Obstetrics and Gynecology, University of Alabama at Birmingham School of Medicine, Birmingham, AL

Zambian Ministry of Health, Lusaka, Zambia

§Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD

The work reported herein was supported in part by the President's Emergency Plan for AIDS Relief through a multicountry grant to the Elizabeth Glaser Pediatric AIDS Foundation from the US Department of Health and Human Services and Centers for Disease Control and Prevention's Global AIDS Program (cooperative agreement U62/CCU12354). Additional investigator salary or trainee support was provided by the National Institutes of Health (D43-TW001035, P30-AI027767, R24-TW007988) and a Clinical Scientist Development Award from the Doris Duke Charitable Foundation (2007061).

The funding agencies played no role in study design, data collection, data analysis, or article writing.

The findings and conclusions included herein are solely the responsibility of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions this article on the journal's Web site (

Correspondence to: Dr Benjamin H. Chi, MD, MSc, Plot 1275 Lubutu Road, PO Box 34681, Lusaka, Zambia (e-mail:

Received April 9, 2011

Accepted July 19, 2011

© 2011 Lippincott Williams & Wilkins, Inc.