Article type
Year
Abstract
Background: Stavudine remains an alternative component of combination antiretroviral therapy (ART) in resource-constrained countries due to limited options, despite attempts to phase it out in order to reduce toxicities. Where stavudine is still in use, it is recommended at a dose lower than the standard dose to reduce toxicities.
Objectives: To compare the safety and virologic efficacy of low-dose versus high-dose stavudine for treating HIV-1 infection.
Methods: A comprehensive search strategy identified randomised controlled trials that compared use of low- versus high-dose stavudine from 1996 to 2014.
Results: 3952 abstracts identified were scanned for relevance. Three trials met the inclusion criteria; all were conducted in developed countries; participants were ART-experienced and all had sustained virologic suppression at baseline. A total of 157 participants were recruited to the trials. Sample sizes ranged from 24 to 92, and more than 79% of participants were male.The studies were at a high risk of selection, performance/detection and selective outcome reporting biases. In light of variation in the design and follow-up of the study results, no meta-analysis was performed and the results of single studies are presented. There was no significant difference in virologic suppression in the included studies (Milinkovic 2007; McComsey 2008; Sanchez-Conde 2005); Risk Ratio (RR) 1.09 (95% CI 0.93 to 1.28), 0.94 (95% CI 0.59 to 1.50) and 1.03 (95% CI 0.90 to 1.18), respectively. Symptomatic hyperlactatemia was seen in the high-dose arm of the Milinkovic 2007 study; RR 0.21 (95% CI 0.01 to 4.66), in no participants in the McComsey 2008 trial. McComsey 2008 and Milinkovic 2007 demonstrated a reduction in bone mineral density, reduction in limb fat and an increase in triglycerides in the high-dose arms.
Conclusions: All three trials identified were conducted in developed countries and none reported from developing countries; enrolled participants were treatment-experienced with sustained virologic suppression and so existing data cannot be generalized to settings where stavudine is currently used in ART-naive patients with high viral loads.
Objectives: To compare the safety and virologic efficacy of low-dose versus high-dose stavudine for treating HIV-1 infection.
Methods: A comprehensive search strategy identified randomised controlled trials that compared use of low- versus high-dose stavudine from 1996 to 2014.
Results: 3952 abstracts identified were scanned for relevance. Three trials met the inclusion criteria; all were conducted in developed countries; participants were ART-experienced and all had sustained virologic suppression at baseline. A total of 157 participants were recruited to the trials. Sample sizes ranged from 24 to 92, and more than 79% of participants were male.The studies were at a high risk of selection, performance/detection and selective outcome reporting biases. In light of variation in the design and follow-up of the study results, no meta-analysis was performed and the results of single studies are presented. There was no significant difference in virologic suppression in the included studies (Milinkovic 2007; McComsey 2008; Sanchez-Conde 2005); Risk Ratio (RR) 1.09 (95% CI 0.93 to 1.28), 0.94 (95% CI 0.59 to 1.50) and 1.03 (95% CI 0.90 to 1.18), respectively. Symptomatic hyperlactatemia was seen in the high-dose arm of the Milinkovic 2007 study; RR 0.21 (95% CI 0.01 to 4.66), in no participants in the McComsey 2008 trial. McComsey 2008 and Milinkovic 2007 demonstrated a reduction in bone mineral density, reduction in limb fat and an increase in triglycerides in the high-dose arms.
Conclusions: All three trials identified were conducted in developed countries and none reported from developing countries; enrolled participants were treatment-experienced with sustained virologic suppression and so existing data cannot be generalized to settings where stavudine is currently used in ART-naive patients with high viral loads.