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Tenofovir in Second-Line ART in Zambia and South Africa: Collaborative Analysis of Cohort Studies

Wandeler, Gilles MD, MSc*,†; Keiser, Olivia PhD*; Mulenga, Lloyd MD‡,§; Hoffmann, Christopher J. MD, MPH‖,¶; Wood, Robin MD#; Chaweza, Thom MD**; Brennan, Alana MPH††,‡‡; Prozesky, Hans MD§§; Garone, Daniela MD‖‖; Giddy, Janet MD¶¶; Chimbetete, Cleophas MD##; Boulle, Andrew MD***; Egger, Matthias MD, MSc*for the IeDEA Southern Africa Collaboration

JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1st, 2012 - Volume 61 - Issue 1 - p 41–48
doi: 10.1097/QAI.0b013e3182632540
Clinical Science

Objectives: Tenofovir (TDF) is increasingly used in second-line antiretroviral treatment (ART) in sub-Saharan Africa. We compared outcomes of second-line ART containing and not containing TDF in cohort studies from Zambia and the Republic of South Africa (RSA).

Methods: Patients aged 16 years and older starting protease-inhibitor–based second-line ART in Zambia (1 cohort) and RSA (5 cohorts) were included. We compared mortality, immunological failure (all cohorts), and virological failure (RSA only) between patients receiving and not receiving TDF. Competing risk models and Cox models adjusted for age, sex, CD4 count, time on first-line ART, and calendar year were used to analyze mortality and treatment failure, respectively. Hazard ratios (HRs) were combined in fixed-effects meta-analysis.

Findings: 1687 patients from Zambia and 1556 patients from RSA, including 1350 (80.0%) and 206 (13.2%) patients starting TDF, were followed over 4471 person-years. Patients on TDF were more likely to have started second-line ART in recent years and had slightly higher baseline CD4 counts than patients not on TDF. Overall, 127 patients died, 532 were lost to follow-up, and 240 patients developed immunological failure. In RSA, 94 patients had virologic failure. Combined HRs comparing TDF with other regimens were 0.60 (95% confidence interval [CI]: 0.41 to 0.87) for immunologic failure and 0.63 (0.38–1.05) for mortality. The HR for virologic failure in RSA was 0.28 (0.09–0.90).

Conclusions: In this observational study, patients on TDF-containing second-line ART were less likely to develop treatment failure than patients on other regimens. TDF seems to be an effective component of second-line ART in southern Africa.

*Division of International and Environmental Health, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland

Clinic for infectious diseases, University Hospital Bern, Bern, Switzerland

Centre for Infectious Disease Research in Zambia, Lusaka, Zambia

§Department of Internal Medicine, Adult Infectious Disease Centre, University Teaching Hospital, Lusaka, Zambia

Aurum Institute for Health Research, Johannesburg, South Africa

Johns Hopkins University School of Medicine, Baltimore, MD

#The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

**Lighthouse Trust Clinic, Kamuzu Central Hospital, Lilongwe, Malawi

††Center for Global Health and Development, Boston University, Boston, MA

‡‡Health Economics and Epidemiology Research Office, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

§§Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa

‖‖Khayelitsha ART Programme, Médecins Sans Frontières, Cape Town, South Africa

¶¶McCord Hospital, Durban, South Africa

##Newlands Clinic, Harare, Zimbabwe

***School of Public Health and Family Medicine, University of Cape Town, South Africa.

Correspondence to: Gilles Wandeler, MD, MSc, Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, CH-3012 Bern, Switzerland (e-mail:

Supported by the National Institute of Allergy and Infectious Diseases Grant 5U01-AI069924-05.

Presented in part at the 13th European AIDS Conference, October 12–15, 2011, Belgrade, Serbia.

The authors have no conflicts of interest to disclose.

G. Wandeler, O. Keiser, and M. Egger designed the study. G. Wandeler and O. Keiser performed the statistical analyses. G. Wandeler and M. Egger wrote the first draft of the manuscript. All authors contributed to the interpretation of the results and to the final version of the manuscript. G. Wandeler had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Received March 26, 2012

Accepted June 5, 2012

© 2012 Lippincott Williams & Wilkins, Inc.