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Has the phasing out of stavudine in accordance with changes in WHO guidelines led to a decrease in single-drug substitutions in first-line antiretroviral therapy for HIV in sub-Saharan Africa?

Brennan, Alana T.; Davies, Mary-Ann; Bor, Jacob; Wandeler, Gilles; Stinson, Kathryn; Wood, Robin; Prozesky, Hans; Tanser, Frank; Fatti, Geoffrey; Boulle, Andrew; Sikazwe, Izukanji; Wools-Kaloustian, Kara; Yiannoutsos, Constantin; Leroy, Valériane; de Rekeneire, Nathalie; Fox, Matthew P.

doi: 10.1097/QAD.0000000000001307
CLINICAL SCIENCE: Epidemiology and Social

Objective: We assessed the relationship between phasing out stavudine in first-line antiretroviral therapy (ART) in accordance with WHO 2010 policy and single-drug substitutions (SDS) (substituting the nucleoside reverse transcriptase inhibitor in first-line ART) in sub-Saharan Africa.

Design: Prospective cohort analysis (International epidemiological Databases to Evaluate AIDS-Multiregional) including ART-naive, HIV-infected patients aged at least 16 years, initiating ART between January 2005 and December 2012. Before April 2010 (July 2007 in Zambia) national guidelines called for patients to initiate stavudine-based or zidovudine-based regimen, whereas thereafter tenofovir or zidovudine replaced stavudine in first-line ART.

Methods: We evaluated the frequency of stavudine use and SDS by calendar year 2004–2014. Competing risk regression was used to assess the association between nucleoside reverse transcriptase inhibitor use and SDS in the first 24 months on ART.

Results: In all, 33 441 (8.9%; 95% confience interval 8.7–8.9%) SDS occurred among 377 656 patients in the first 24 months on ART, close to 40% of which were amongst patients on stavudine. The decrease in SDS corresponded with the phasing out of stavudine. Competing risks regression models showed that patients on tenofovir were 20–95% less likely to require a SDS than patients on stavudine, whereas patients on zidovudine had a 75–85% decrease in the hazards of SDS when compared to stavudine.

Conclusion: The decline in SDS in the first 24 months on treatment appears to be associated with phasing out stavudine for zidovudine or tenofovir in first-line ART in our study. Further efforts to decrease the cost of tenofovir and zidovudine for use in this setting is warranted to substitute all patients still receiving stavudine.

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aDepartment of Global Health, Boston University, Boston, Massachusetts, USA

bHealth Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

cDepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA

dCentre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa

eDepartment of Infectious Diseases, Bern University Hospital, University of Bern

fInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland

gThe Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town

hDivision of Infectious Diseases, Department of Medicine, University of Stellenbosch & Tygerberg Academic Hospital, Cape Town

iAfrica Center for Health and Population Studies, University of Kwazulu-Natal

jKheth’Impilo AIDS Free Living, Cape Town

kDepartment of Health, Provincial Government of the Western Cape, Cape Town, South Africa

lCenter for Infectious Disease Research in Zambia, Lusaka, Zambia

mIndiana University School of Medicine, Indianapolis

nRichard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, USA

oINSERM U1027, Université Paul Sabatier Toulouse 3, Toulouse

pUniversité Bordeaux, ISPED, Centre INSERM U1219 Epidémiologie-Biostatistique, Bordeaux, France.

Correspondence to Alana T. Brennan, Department of Global Health Boston University Crosstown Center, 3rd Floor, 801 Massachusetts Ave, Boston, MA 02118, USA. Tel: +1 617 414 1179; e-mail:

Received 18 May, 2016

Revised 22 September, 2016

Accepted 5 October, 2016

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