Abstract
Objectives: To compare the immunological and clinical effects of a further reduction of stavudine dose to 30 mg once-daily with that of a standard zidovudine containing antiretroviral therapy (ART) regimen in a prospective, open-label randomized controlled study. Methods: Naive HIV infected patients were equally randomized to receive either stavudine 30 mg once-daily or a standard dose zidovudine containing regimen. CD4+ T-cell counts, Haemoglobin (Hb), alanine aminotransferase (ALT), Body Mass Index (BMI), WHO stage and patients’ morbidity at baseline, three and six months were determined. Changes between baseline and three as well as six months follow-up were compared within-and between-groups. Results: Five hundred and twenty patients aged ≥ 18 years were included. Males were 159 (30.6%), with the mean (SD) age of 39 (9) years. Within group comparison indicated that there were statistically significant increases in mean CD4+ cell counts, BMI, and Hb (p<0.0001) at 3 and 6 months from the values at baseline in both groups, but there were not significantly different between groups. Furthermore, there was no statistically significant difference between groups in terms of occurrence of opportunistic infections (OIs) however, there was significant decrease of OIs for subsequent follow up time points compared to baseline status. The overall median adherence rate was 94% (IQR 94%, 98%) in both groups, but patients in the stavudine group had better adherence compared to those in the zidovudine group, p<0.0001. Additionally, liver damage at 6 months, as indicated by elevated ALT, was more likely with the zidovudine based regimen, p <0.0001. There was no statistically significant difference in ALT elevations between the groups at 3 months. Conclusion: The immunological and clinical outcomes following a regimen employing a reduced dose of stavudine to 30 mg once-daily were similar to those of a standard zidovudine-based antiretroviral regimen.
Highlights
Stavudine has been widely used for HIV treatment in resource-limited countries due to its low cost [1,2], favorable early tolerability, convenient drug administration, and minimal requirements for laboratory monitoring [3].Stavudine inhibits mitochondrial DNA polymerase of adipocyte tissue, heart, nerve, liver and pancreatic cells [4], and this inhibition causes cumulative toxicity resulting in lipodystrophy especially lipoatrophy [5]
Peripheral neuropathy (PNP) and lactic acidosis are mostly encountered by patients on stavudine based regimen [6] while the other stavudine related adverse effects include cardiomyopathy, headache, rashes and pancreatitis [1,7]
Allocation of patients to a particular study group was randomly generated by a randomization software developed by Saghaei [17].While the software did a random allocation of 520 patients in a ratio of 1:1, block randomization was done in the blocks of twentieths, each block maintained the ration of 1:1
Summary
Stavudine has been widely used for HIV treatment in resource-limited countries due to its low cost [1,2], favorable early tolerability, convenient drug administration, and minimal requirements for laboratory monitoring [3].Stavudine inhibits mitochondrial DNA polymerase of adipocyte tissue, heart, nerve, liver and pancreatic cells [4], and this inhibition causes cumulative toxicity resulting in lipodystrophy (known as HIV lipodystrophy) especially lipoatrophy [5]. Stavudine has been widely used for HIV treatment in resource-limited countries due to its low cost [1,2], favorable early tolerability, convenient drug administration, and minimal requirements for laboratory monitoring [3]. While there is concern about stavudine related toxicity, some low income countries are still using stavudine based regimens among their combinations, because of budgetary constraints [2,10]. Complete phasing out of stavudine based regimens in countries like Tanzania which has serious budgetary constraints will likely limit access to antiretroviral therapy, and may raise HIV infection incidence and HIV/AIDS related deaths. A change from stavudine based regimens to other regimens has about 50% or more increase in the cost per person per annum [11], and in some countries phasing out of stavudine has not been implemented completely [8,10]
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