Efficacy and tolerability of low dose stavudine in HIV-infected patients attending a Referral Hospital in Kenya

Abstract

Background Stavudine is widely used in developing countries due to its low cost, availability in fixed dose combinations and better initial tolerability compared to zidovudine. However, it is associated with mitochondrial toxicity which leads to peripheral neuropathy, lipodystrophy and lactic acidosis. To minimize these toxicities, the Kenyan government adopted the 2007 WHO recommendations on use of stavudine at a reduced dose of 30mg twice daily in all HIV infected adults irrespective of weight. However the efficacy and safety of this reduced dose has only been evaluated in Western settings in ART-experienced patients with stable CD4 counts and viral loads using some regimens which are different from those recommended by the WHO for use in developing countries. Therefore studies to evaluate the efficacy and tolerability of stavudine at the reduced dose in ART-naIve patients on standard first line regimens in Kenya are necessary. Objective To compare the efficacy and tolerability of 40 mg and 30 mg twice daily stavudine in ART-naIve HIV-infected adult patients. Study design This was a retrospective cohort study carried out at the Kenyatta National Hospital Comprehensive Care Centre. Population The study population was ART-naive adult patients initiated on standard first line regimens containing stavudine between January 2006 and December 2008. The study population was divided into three groups. The first two groups comprised patients weighing > 60 kg and treated with either 30 mg or 40 mg twice daily stavudine. The third group included patients weighing < 60 kg treated with 30 mg twice daily stavudine. pie size The minimum sample size was calculated as 235 patients in each treatment group. A total of 810 patients met the inclusion criteria for the study. Data analysis Data collected were analyzed using SPSS 13.0 software. Descriptive data analysis was done on all variables and compared across the study arms. The Chi-squared test was used to compare the proportion of categorical variables across and within study arms. Association effects were determined by use of Chi-square tests and controlling for the variable using Mantel and Haenszel tests. Cox proportional hazard models (PHM) were used to determine the effects of independent variables upon the time an event was observed. In patients weighing > 60 kg, the incidence of peripheral neuropathy was higher in the group treated with 40 mg compared to those treated with 30 mg twice daily stavudine (23.3 % versus 13 %, HR=1.81, CI=1.06-3.08, p=0.003). It was also observed that in patients treated with 30 mg stavudine, those weighing < 60 kg had a higher incidence of peripheral neuropathy compared to those weighing > 60 kg (24.2 versus13%, HR=2.19, CI=1.34 - 3.58, p=0.002). There was no statistically significant difference in median change in CD4 cell counts between the three treatment groups (p=0.795). Conclusion Treatment with 30 mg stavudine in patients weighing > 60 kg led to improved tolerability and similar efficacy compared to the 40 mg stavudine. This finding further augments the current WHO recommendation to reduce the dose of stavudine from 40 mg to 30 mg in patients weighing > 60 kg, However in patients weighing < 60 kg, treatment with 30 mg stavudine is still associated with high incidences of peripheral neuropathy and lipodystrophy compared to patients treated with the same dose weighing > 60 kg. There is therefore a need to evaluate efficacy and tolerability of lower doses of stavudine in this treatment group.