The Effect of 30 vs. 40mg of Stavudine vs. Tenofovir on Treatment Outcomes amongst HIV-positive Patients in Johannesburg, South Africa

By  Alana Brennan  Dr Mhairi Maskew  Professor Ian Sanne  Dr. Matthew Fox  |  | 


Background: In 2007 the WHO recommended reducing stavudine (d4T) dosage from 40 to 30mg for all HIV-positive adults on antiretroviral therapy (ART) and in 2009 recommended discontinuing d4T for initial HIV treatment due to side effects. Although many resource-limited countries have changed treatment guidelines to substitute tenofovir (TDF) for d4T, in others, d4T is still used. Therefore, determining the effect on treatment outcomes, specifically single-drug substitutions, of reduced dose d4T vs. TDF remains important. Methods: Prospective cohort analysis examining the association between TDF and d4T (30mg and 40mg) on single-drug substitutions from January 2007 to May 2011 at the Themba Lethu Clinic in Johannesburg, South Africa. A substitution is defined as replacing d4T with zidovudine, TDF or abacavir and TDF with d4T, zidovudine or abacavir without initiating a protease inhibitor. For d4T patients we restricted the analysis to those weighing >60kg at baseline. Log-binomial regression was used to identify predictors of single-drug substitutions in the first year on ART. Results: 5,952 treatment naïve patients >18 years were eligible for our analysis, 2,765 (46.5%) initiated TDF, 2,667 (44.8%) 30mg d4Tand 520 (8.7%) 40mg d4T, respectively. The trend in d4T- and TDF-based initiating regimens were in-line with WHO recommendations. A total of 516 (8.7%; 95% CI: 8.0-9.4%) single-drug substitutions occurred over follow-up, 76 (2.7%; 95% CI: 2.2-3.4%) occurred amongst TDF patients, 348 (13.1%; 95% CI: 11.8-14.4%) and 92 (17.7%; 95% CI: 14.6-21.2%) amongst those on 30 and 40mgs of d4T, respectively. The most common reasons for substitutions were d4Trelated toxicities; neuropathy (15.7%), lipodystrophy (14.5%) and hyperlactatemia/lactic acidosis (10.1%). D4T related toxicities were greater among those on 40mg vs. 30mg; neuropathy-31.2% vs. 10.3%, hyperlactatemia/lactic acidosis-13.0% vs. 3.1% and lipodystrophy-17.4% vs. 13.0%, respectively. Adjusted log-binomial regression model showed patients on 30mg (RR 7.4; 95%CI: 5.0-10.9) and 40mg (RR 11.0; 95%CI: 6.7-18.0) of d4T were at higher risk of single-drug substitutions vs. TDF patients in the first 12-months on ART.  Conclusion: In resource-limited settings where drug alternatives are not available, treatment simplification with TDF may lower drug related adverse events and reduce the need for clinical expert supervision.

Conference: CROI conference 2013, Atlanta, USA

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