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?


Authors

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.


Journal

AIDS. 2016 Oct 20. [Epub ahead of print]


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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