Background: Although tenofovir and stavudine have performed equally well with respect to viral suppression, tenofovir has been associated with less toxicity than stavudine. We investigated whether single-drug substitutions have decreased with the introduction of tenofovir into standard first-line therapy in South Africa in 2010. Methods: Prospective cohort analysis examining the yearly trend in single-drug substitutions from April 2004-June 2011 at the Themba Lethu Clinic in Johannesburg, South Africa. First-line ART prior to April 2010 consisted of stavudine or zidovudine with lamivudine and efavirenz or nevirapine. In April 2010, tenofovir was substituted for stavudine. A single-drug substitution is defined as changing one or more drugs without initiating a protease inhibitor. Log-binomial regression was used to identify predictors of one-year single-drug substitutions. Results: 17,907 treatment naïve patient, >18 initiated ART. 2,255 (12.6%; 95% CI: 12.1-13.1) single-drug substitutions occurred over follow-up. Prior to 2010 one year rates of single-drug substitutions ranged from 13.1-14.9% (Table). In 2010, when the switch to tenofovir occurred, a slight decrease occurred (11.0%) and a substantial drop in 2011 (6.1%). We observed fewer substitutions amongst patients on a tenofovir-based regimen (5.5%; 95%CI: 4.7-6.4%) vs. zidovudine- (12.6%; 95% CI: 10.5-14.9%) and stavudine-based (13.9%; 95%CI: 13.4-14.6%). The most common reasons for substitutions were stavudine related drug toxicities neuropathy (22.8%), hyperlactatemia/lactic acidosis (9.8%) and lipodystrophy (8.8%). We also identified tenofovir (3.3% renal insufficiency) and zidovudine (2.0% anemia) related toxicities. Between 2005 and 2011, neuropathy decreased from 35% to 1.2%, hyperlactatemia/lactic acidosis from 13.3% to 0% and lipodystrophy from 14.4% to 1.7%. Adjusted models showed females (RR 1.5; 95% CI: 1.4-1.7), patients <40 years of age (RR 1.1; 95% CI: 1.0-1.2) and those on a zidovudine-based (RR 2.7; 95% CI: 1.9-3.9) or stavudine-based (RR 3.6; 95% CI: 2.8-4.6) regimens were at increased risk of a single-drug substitution (vs. tenofovir-based regimens) in the first 12-months on ART. Conclusions: A decline in one-year rates of single-drug substitutions coincided with a switch to tenofovir over stavudine in first-line regimens. The increased use of tenofovir could lead to improved regimen durability in resource-limited settings.
Conference: IWHOD 2013, Cavtat, Croatia