HIV-infected adults aged 65 years or older. However, among 12,000 people over the age of 65, 30% developed peripheral neuropathy. Additionally, since the elderly are more likely to have decreased renal function, they are more likely to develop toxic side effects. Adverse events Common side effects Nausea Vomiting Diarrhea Headache Upset stomach Severe side effects Peripheral neuropathy Lactic acidosis Pancreatitis Hepatotoxicity Hepatomegaly with steatosis Lipoatrophy/lipodystrophy (fat redistribution/accumulation) Individuals are monitored for the development of these serious adverse effects. The development of peripheral neuropathy is shown to be dose related, and may be resolved if the drug is discontinued. Individuals with advanced HIV-1 disease, a history of peripheral neuropathy, or individuals on other drugs that have association with neuropathy develop this side effect more often. Stavudine has been shown in laboratory test to be genotoxic, but with clinical doses its carcinogenic effects are non-existent. Hyperlactatemia, bone mineral density (BMD) loss, reduction in limb fat and an increase in triglycerides were found when administered in high dosages. It is also one of the most likely antiviral drugs to cause lipodystrophy, and for this reason it is no longer considered an appropriate treatment for most patients in developed countries. HLA-B*4001 may be used as a genetic marker to predict which patients will develop stavudine-associated lipodystrophy, to avoid or shorten the duration of stavudine according to a study in Thailand. It is still used as first choice in first line therapy in resource poor settings such as in India. Only in case of development of peripheral neuropathy or pregnancy is it changed to the next choice, zidovudine. Safety and effectiveness of dosage titration was not reported in treatment naive patients. It was only reported in those patients with sustained virologic suppression. These findings are not generalized to Stavudine used in ART naive patients who have high viral loads. On Monday 30 November 2009, the World Health Organization stated that "[The WHO] recommends that countries phase out the use of Stavudine, or d4T, because of its long-term, irreversible side-effects. Stavudine is still widely used in first-line therapy in developing countries due to its low cost and widespread availability. Zidovudine (AZT) or tenofovir (TDF) are recommended as less toxic and equally effective alternatives." Mechanism of action Stavudine is a nucleoside analog of thymidine. It is phosphorylated by cellular kinases into an active triphosphate. Stavudine triphosphate inhibits HIV's reverse transcriptase by competing with the natural substrate, thymidine