Long-term administration of 3?-Azido-2?,3?-dideoxythymidine to patients with AIDS-related neurological disease

Abstract

3'-Azido-2',3'-dideoxythymidine (AZT) has been administered to 7 patients with human immunodeficiency virus-associated neurological disease: 3 with dementia, 2 with peripheral neuropathy, 1 with dementia and peripheral neuropathy, and 1 with T-10 paraplegia. Six of the patients showed improvement in their neurological dysfunction on being administered AZT, as assessed by clinical evaluation, neuropsychological testing, nerve conduction studies, and/or positron emission tomographic scans. Three of these 6 patients showed sustained improvement 5 to 18 months after the initiation of AZT therapy. These results suggest that certain human immunodeficiency virus-associated neurological abnormalities are at least partially reversible following the administration of antiretroviral therapy and provide a rationale for further studies using antiretroviral chemotherapy.

Use of Accelerator Mass Spectrometry to Measure the Pharmacokinetics and Peripheral Blood Mononuclear Cell Concentrations of Zidovudine

“…6,7 The US FDA approved ZDV in 1987 for the treatment of patients with HIV infection, and it remains a component of many recommended initial treatment regimens.…”

Brain Targeting of anti-HIV Nucleosides:in vitro and in vivoEvaluation of 6-chloro-2′,3′-dideoxypurine, a Lipophilic Prodrug of 2′,3′-dideoxyinosine

“…Regardless of the mechanism of the origin of the dementia, it is widely believed that the development of anti-HIV drugs that penetrate the blood-brain barrier and suppress viral multiplication is needed. Zidovudine (AZT) has been shown partially to reverse dementia in AIDS patients (Klecker et al, 1987;Fiala et al, 1988;Yarchoan et al, 1988). However, it is not known to what extent AZT penetrates the blood-brain barrier and, furthermore, whether the levels of AZT are sufficient for suppression of HIV replication in the brain.…”

AIDS dementia complex

“…Several controlled clinical studies are now under way to assess its role in halting the progression oflllV -induced brain disease and to determine if the neurologic disturbances of AIDS dementia complex can be reversed by its use. [10][11][12] Summary A common complication of acquired immunodeftclency syndrome (AIDS) is being increasingly recognized. Known as AIDS dementia complex, the disorder is characterized by global impairment of intellectual and cognitive functions, personality and behavioral disturbances, and motor dysfunction manifested by impaired speech, gait, and coordination.…”