Deoxythymidine nucleoside analogue
| Clinical Use|
| Use in Initial vs Subsequent Therapy|
Treatment guidelines of the U.S. Department of Health and Human Services state that stavudine is "not recommended" for initial treatment of HIV infection because of a high rate of toxicity, including peripheral neuropathy, lipoatrophy, and lactic acidosis.
A direct comparison of stavudine with zidovudine, each in combination with lamivudine and indinavir as initial therapy, found no difference in the two regimens in maintaining viral load suppression at 48 weeks.(1) Although rates of serious adverse events were not significantly different between treatment arms, there was increased nausea and vomiting in the zidovudine-containing arm, and increased diarrhea and rash in the stavudine-containing arm.
A comparison of stavudine with tenofovir, each combined with lamivudine and efavirenz in initial therapy, showed similar rates of viral suppression at 48 and 96 weeks (HIV RNA <50 copies/mL in 74% of stavudine recipients vs 78% of tenofovir recipients at 96 weeks), but higher rates of adverse effects in the stavudine group.(2)
A comparison of stavudine with emtricitabine, each combined with didanosine and efavirenz in antiretroviral-naive patients, showed significantly lower rates of virologic suppression at 48 weeks in the stavudine arm (HIV RNA <50 copies/mL in 59% of stavudine recipients vs 78% of emtricitabine recipients; p < .001). The mean CD4 increase was lower in stavudine recipients, but this difference was not statistically significant (120 cells/µL in the stavudine group vs 153 cells/µL in the emtricitabine group; p = .15).(3)
| Potential Adverse Effects|
Symptomatic side effects of stavudine include peripheral neuropathy, which may range in severity from mild to disabling, and pancreatitis. Nucleoside analogues are associated with mitochondrial toxicity leading to potentially serious long-term side effects such as lactic acidosis, lipodystrophy, and disorders of lipid metabolism.(4) Stavudine appears to contribute to these disorders more often than other nucleoside analogues.(2,5,6) The combination of stavudine + didanosine has additive toxicity and should be avoided, when possible; in particular, this combination should not be used in pregnant women if other options are available.(3,6,7,8) It is important to assess patient motivation and discuss possible side effects and strategies for their management before treatment with stavudine is initiated.
| Interactions with Other Drugs|
Clinically significant drug-drug interactions involving stavudine appear to be uncommon, but stavudine should not be administered concurrently with certain medications because of potential additive or overlapping adverse effects. For example, the combination of stavudine and didanosine should be avoided because of increased risk of peripheral neuropathy and hyperlactatemia, and should not be used for pregnant women because of reports of lactic acidosis with pancreatitis or hepatic steatosis.
Patients receiving stavudine together with other potentially neurotoxic drugs (such as ribavirin, isoniazid, or vincristine) should be monitored closely for the development of neuropathic symptoms.
Stavudine and zidovudine should not be used in combination because they compete with each other for activation by intracellular phosphorylation, resulting in diminished antiviral activity.(9)
|| || Squires KE, Gulick R, Tebas P, et al. A comparison of stavudine plus lamivudine versus zidovudine plus lamivudine in combination with indinavir in antiretroviral naive individuals with HIV infection: selection of thymidine analog regimen therapy (START I). AIDS. 2000 Jul 28;14(11):1591-600.|
|| || Gallant JE, Staszewski S, Pozniak AL, et al; 903 Study Group.Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA. 2004 Jul 14;292(2):191-201.|
|| || Saag MS, Cahn P, Raffi F, et al; FTC-301A Study Team. Efficacy and safety of emtricitabine vs stavudine in combination therapy in antiretroviral-naive patients: a randomized trial. JAMA. 2004 Jul 14;292(2):180-9.|
|| || Moyle G. Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity. Clin Ther. 2000 Aug;22(8):911-36; discussion 898.|
|| || Joly V, Flandre P, Meiffredy V, et al. Increased risk of lipoatrophy under stavudine in HIV-1-infected patients: results of a substudy from a comparative trial. AIDS. 2002 Dec 6;16(18):2447-54.|
|| || Boubaker K, Flepp M, Sudre P, et al. Hyperlactatemia and antiretroviral therapy: the Swiss
HIV Cohort Study. Clin Infect Dis. 2001 Dec 1;33(11):1931-7.|
|| || Robbins GK, De Gruttola V, Shafer RW, et al. Comparison of sequential three-drug regimens as
initial therapy for HIV-1 infection. N Engl J Med. 2003 Dec 11;349(24):2293-303.|
|| ||ZERIT (stavudine) package insert, Bristol-Myers Squibb Virology.|
|| || Havlir DV, Tierney C, Friedland GH, et al. In vivo antagonism with zidovudine plus stavudine combination therapy. J Infect Dis. 2000 Jul;182(1):321-5.|