Stavudine:pharmacology,clinical use and future role

Abstract

Stavudine is a nucleoside analogue reverse transcriptase inhibitor of HIV-1 and HIV-2 and demonstrates in vitro activity with an acceptable therapeutic index in a range of T-lymphocyte and haematopoietic precursor cell lines. It is additive or synergistic in vitro with a range of other antiretrovirals, including the proteinase inhibitor saquinavir, in two- and three-way combinations and is active against zidovudine (ZDV)-resistant virus. It exhibits excellent oral bioavailability, with cerebrospinal fluid (CSF)/plasma penetration. In clinical use, stavudine monotherapy exhibits similar antiretroviral activity to ZDV, and is of proven clinical benefit in ZDV-pre-treated patients. In combination with ddI and/or nelfinavir it results in more substantial and durable responses in immunological and virological markers than reported with either drug alone. Further data on stavudine in combination with other antiretrovirals are now awaited. Comparative trials in ZDV-experienced patients suggest a similar frequency of adverse events to that observed with ZDV. Peripheral neuropathy is the most common dose-limiting toxicity, with haematological and hepatic function disturbance being infrequent. Resistance to stavudine develops slowly in vitro and in vivo but may lead to co-resistance to ZDV or ddI. Stavudine will be used clinically as a combination agent both in initial therapy and in patients with prior ZDV experience.

A secondary data analysis of qualitative study of individualized treatment regimen for North Indians living with human immunodeficiency virus-1

“…Stavudine exhibits antiretroviral activity as a monotherapy or combination therapy to manage the adults with HIV infection [20] The rate of treatment failure for stavudine/lamivudine /nevirapine was determined in Asian region [21]. In this study, out of 11 North Indian patients on SLE/SLN combination therapy, 9 North Indian patients were developed resistance to stavudine.…”

A secondary data analysis of qualitative study of individualized treatment regimen for North Indians living with human immunodeficiency virus-1

“…Stavudine exhibits antiretroviral activity as a monotherapy or combination therapy to manage the adults with HIV infection 20 . The rate of treatment failure for stavudine/lamivudine /nevirapine was determined in Asian region 21 .…”

Stavudine Resistance: An Update on Susceptibility following Prolonged Therapy

“…The only notable dose-limiting toxicity is peripheral neuropathy; mild macrocytosis and hepatic function disturbances are seen occasionally. These sideeffects are observed largely in patients with advanced HIV disease [25][26][27][28]. The drug has been shown in several clinical trials to increase CD4 cell numbers and decrease viral titres in HIV-infected individuals [25][26][27][28][29].…”

“…These sideeffects are observed largely in patients with advanced HIV disease [25][26][27][28]. The drug has been shown in several clinical trials to increase CD4 cell numbers and decrease viral titres in HIV-infected individuals [25][26][27][28][29]. It is particularly effective when used in combination with another nucleoside analogue and a protease inhibitor [30].…”