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.
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.
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.
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.
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.
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.