Treatment Of Human Immunodeficiency Virus Disease Research Articles

Clinical pharmacokinetics of zidovudine. An update.

The battle against the acquired immune deficiency syndrome (AIDS) is now into its second decade, and substantial advancements have been made in our understanding of the complex life cycle of, and the immunopathology associated with, human immunodeficiency virus (HIV) infection, as well as of the drugs used to modify the course of disease. Zidovudine was the first agent approved for treatment of HIV disease, and since its widespread availability in 1987 the pharmacokinetic disposition and clinical effects of zidovudine have been extensively evaluated. This article reviews the absorption, distribution, metabolism and elimination characteristics of zidovudine, focusing on more recent information. In addition, factors that may or may not affect zidovudine disposition are discussed. These include selected drug interactions and concomitant disease states such as renal and hepatic insufficiency. Issues such as bodyweight normalisation, maternal-fetal transfer, pregnancy and intracellular phosphorylation are discussed in relation to the pharmacokinetics and clinical efficacy of zidovudine. Finally, information regarding the clinical pharmacodynamics of zidovudine is presented. This includes possible relationships between zidovudine pharmacokinetics and markers of efficacy and toxicity, and the significance of linking pharmacokinetic and pharmacodynamic information.

Diagnosis and treatment of substance use disorders in patients with HIV infection

Drug users infected with the human immunodeficiency virus (HIV) are a rapidly growing group of patients whose optimal medical and psychiatric care requires that the substance use disorders are assessed and treated. Drug users have high rates of other psychiatric disorders even in the absence of HIV infection. The effects of acute and chronic drug use complicate the assessment of psychiatric symptoms. There is evidence that in the early stages of HIV disease, drug use plays a larger role in producing psychiatric disorders than does HIV itself. In general, neuropsychiatric problems do not appear to progress more rapidly in drug users than in HIV infected homosexual men. However, compliance with and adherence to medical care are major problems in the treatment of drug users. The combined treatment of substance use and psychiatric disorders may improve the likelihood that patients will receive adequate medical treatment of HIV disease, particularly if integrated systems of care are in place.

Rehabilitation management of the lower extremity in HIV disease.

The sequelae of human immunodeficiency virus (HIV) disease include a host of devastating conditions involving the lower extremity. These include rheumatologic dysfunction, Kaposi's sarcoma, peripheral neuropathies, and skin ulcers. Pain, weakness, and loss of range of motion caused by these conditions can lead to changes in gait pattern, loss of mobility and function, and limited quality of life. The role of the rehabilitation specialist in the care and treatment of HIV disease as it affects the lower extremity, and the treatment strategies, precautions, and suggestions will be discussed.

Regulation of HIV expression by viral genes and cytokines.

The human immunodeficiency virus (HIV) is the causative agent of the acquired immunodeficiency syndrome (AIDS), a leading cause of death among young individuals. As a complex pathogenic retrovirus, HIV is characterized in vitro and in vivo by the ability to establish either a latent or productive infection of CD4+ T lymphocytes and mononuclear phagocytes (MPs). Viral latency and expression are under the control of both viral genes and several host-related factors. Among these latter, several proinflammatory and immunoregulatory cytokines profoundly affect HIV replication in T lymphocytes and MPs in vitro. Because many of these cytokines have been found to be elevated in HIV-infected individuals, it is likely that they act as regulators of viral expression in vivo. Both viral genes and cytokines regulate transcriptional and posttranscriptional steps in HIV replication. Thus, it is likely that common regulatory pathways between these two distinct classes of regulator molecules will be identified in the near future and will provide potential targets for pharmacologic intervention and treatment of HIV disease.