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?

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

OBJECTIVE:: We assessed the relationship between phasing out stavudine in first-line antiretroviral therapy(ART) in accordance with World Health Organization 2010 policy and single-drug substitutions (SDS)(substituting the nucleoside reverse transcriptase inhibitor(NRTI) in first-line ART) in sub-Saharan Africa. DESIGN:: Prospective cohort analysis (IeDEA-Multiregional) including ART-naïve, HIV-infected patients ≥16 years initiating ART between January 2005-December 2012. Before April 2010 (July 2007 in Zambia) national guidelines called for patients to initiate stavudine-based or zidovudine-based regimen, while after 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 NRTI use and SDS in the first 24 months on ART. RESULTS:: 33,441 (8.9%; 95% CI: 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% to 95% less likely to require a SDS than patients on stavudine, while patients on zidovudine had a 75% to 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.

Original languageEnglish (US)
JournalAIDS
DOIs
StateAccepted/In press - Oct 20 2016

Fingerprint

Drug Substitution
Stavudine
Africa South of the Sahara
Tenofovir
HIV
Guidelines
Zidovudine
Therapeutics
Reverse Transcriptase Inhibitors
Nucleosides
Zambia
Cohort Studies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

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; Wool-Kaloustian, Kara; Yiannoutsos, Constantin; Leroy, Valériane; de Rekeneire, Nathalie; Fox, Matthew P.

In: AIDS, 20.10.2016.

Research output: Contribution to journalArticle

Brennan, AT, Davies, MA, Bor, J, Wandeler, G, Stinson, K, Wood, R, Prozesky, H, Tanser, F, Fatti, G, Boulle, A, Sikazwe, I, Wool-Kaloustian, K, Yiannoutsos, C, Leroy, V, de Rekeneire, N & Fox, MP 2016, '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?', AIDS. https://doi.org/10.1097/QAD.0000000000001307
Brennan, Alana T. ; Davies, Mary Ann ; Bor, Jacob ; Wandeler, Gilles ; Stinson, Kathryn ; Wood, Robin ; Prozesky, Hans ; Tanser, Frank ; Fatti, Geoffrey ; Boulle, Andrew ; Sikazwe, Izukanji ; Wool-Kaloustian, Kara ; Yiannoutsos, Constantin ; Leroy, Valériane ; de Rekeneire, Nathalie ; Fox, Matthew P. / 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?. In: AIDS. 2016.
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title = "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?",
abstract = "OBJECTIVE:: We assessed the relationship between phasing out stavudine in first-line antiretroviral therapy(ART) in accordance with World Health Organization 2010 policy and single-drug substitutions (SDS)(substituting the nucleoside reverse transcriptase inhibitor(NRTI) in first-line ART) in sub-Saharan Africa. DESIGN:: Prospective cohort analysis (IeDEA-Multiregional) including ART-na{\"i}ve, HIV-infected patients ≥16 years initiating ART between January 2005-December 2012. Before April 2010 (July 2007 in Zambia) national guidelines called for patients to initiate stavudine-based or zidovudine-based regimen, while after 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 NRTI use and SDS in the first 24 months on ART. RESULTS:: 33,441 (8.9{\%}; 95{\%} CI: 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{\%} to 95{\%} less likely to require a SDS than patients on stavudine, while patients on zidovudine had a 75{\%} to 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.",
author = "Brennan, {Alana T.} and Davies, {Mary Ann} and Jacob Bor and Gilles Wandeler and Kathryn Stinson and Robin Wood and Hans Prozesky and Frank Tanser and Geoffrey Fatti and Andrew Boulle and Izukanji Sikazwe and Kara Wool-Kaloustian and Constantin Yiannoutsos and Val{\'e}riane Leroy and {de Rekeneire}, Nathalie and Fox, {Matthew P.}",
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T1 - 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?

AU - Brennan, Alana T.

AU - Davies, Mary Ann

AU - Bor, Jacob

AU - Wandeler, Gilles

AU - Stinson, Kathryn

AU - Wood, Robin

AU - Prozesky, Hans

AU - Tanser, Frank

AU - Fatti, Geoffrey

AU - Boulle, Andrew

AU - Sikazwe, Izukanji

AU - Wool-Kaloustian, Kara

AU - Yiannoutsos, Constantin

AU - Leroy, Valériane

AU - de Rekeneire, Nathalie

AU - Fox, Matthew P.

PY - 2016/10/20

Y1 - 2016/10/20

N2 - OBJECTIVE:: We assessed the relationship between phasing out stavudine in first-line antiretroviral therapy(ART) in accordance with World Health Organization 2010 policy and single-drug substitutions (SDS)(substituting the nucleoside reverse transcriptase inhibitor(NRTI) in first-line ART) in sub-Saharan Africa. DESIGN:: Prospective cohort analysis (IeDEA-Multiregional) including ART-naïve, HIV-infected patients ≥16 years initiating ART between January 2005-December 2012. Before April 2010 (July 2007 in Zambia) national guidelines called for patients to initiate stavudine-based or zidovudine-based regimen, while after 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 NRTI use and SDS in the first 24 months on ART. RESULTS:: 33,441 (8.9%; 95% CI: 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% to 95% less likely to require a SDS than patients on stavudine, while patients on zidovudine had a 75% to 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.

AB - OBJECTIVE:: We assessed the relationship between phasing out stavudine in first-line antiretroviral therapy(ART) in accordance with World Health Organization 2010 policy and single-drug substitutions (SDS)(substituting the nucleoside reverse transcriptase inhibitor(NRTI) in first-line ART) in sub-Saharan Africa. DESIGN:: Prospective cohort analysis (IeDEA-Multiregional) including ART-naïve, HIV-infected patients ≥16 years initiating ART between January 2005-December 2012. Before April 2010 (July 2007 in Zambia) national guidelines called for patients to initiate stavudine-based or zidovudine-based regimen, while after 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 NRTI use and SDS in the first 24 months on ART. RESULTS:: 33,441 (8.9%; 95% CI: 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% to 95% less likely to require a SDS than patients on stavudine, while patients on zidovudine had a 75% to 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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