Back to Browse Journals » Neurobehavioral HIV Medicine » Volume 3

Anti-HIV-1 drug toxicity and management strategies

Authors Sharma B

Published Date April 2011 Volume 2011:3 Pages 27—40

DOI http://dx.doi.org/10.2147/NBHIV.S11748

Published 28 April 2011

Bechan Sharma
Department of Biochemistry, University of Allahabad, Allahabad, India

Abstract: Antihuman immunodeficiency virus type 1 (anti-HIV-1) medications have helped millions of HIV-1-infected people lead longer and healthier lives. The goal of HIV-1 treatment is to reduce the number of virions in the body of infected individuals and to prevent rapid destruction of CD4+ T-lymphocyte cells, thus protecting the immune system. Most of the anti-HIV-1 drugs in practice are designed using viral reverse transcriptase (HIV-1RT), protease, and integrase as targets. These drugs that inhibit the activities of HIV-1RT, viral protease, and integrase are therefore known as anti-HIV-1RT, antiprotease, and anti-integrase molecules, respectively. The US Food and Drug Administration has approved 22 anti-HIV-1/acquired immunodeficiency syndrome (AIDS) drugs for clinical use by HIV-1-infected individuals and AIDS patients. Among the drugs, most of the nucleoside analogs (excluding two isomers of 3TC, (-)3TC and (+)3TC, which are shown to be less toxic in cell culture) exhibit clinical complications that pose a threat to chemotherapy. The toxicity of these molecules arises due to their negative impact on the activities of human mitochondrial chromosomal DNA polymerases (a, d, ß, and e) in general and DNA polymerase γ in particular. Other anti-HIV-1 regimens are also reported to cause toxicity. The range of toxicity extends from mild to life-threatening levels. The prolonged use of zidovudine (3′-azido-3′-deoxythymidine [AZT] or Retrovir), which was first approved in 1987 as a nucleoside analog reverse transcriptase inhibitor, has been reported to cause severe hematologic toxicity, including severe anemia, granulocytopenia, and symptomatic myopathy. Many other drugs that are often used in combination with AZT have similar toxicities. The newer antiretrovirals (ARVs), such as 2′,3′-dideoxycytidine, 2′,3′-dideoxyinosine, and 2′,3′-dideoxy-2′,3′-didehydrothymidine, which exhibit analogous mechanisms of action and similar toxicities to AZT, have not been studied extensively. Acyclovir and gancyclovir can cause severe nausea and vomiting. Some of these ARVs when taken during pregnancy may generate teratogenic effects. Similarly, use of antiproteases in highly active ARV therapy causes hepatotoxicity, which poses a severe risk to the patients. In addition, application of fusion inhibitors and anti-integrases induces strong side effects in HIV-1-infected or AIDS patients. The present review illustrates a comprehensive analysis of the existing literature on the toxicity of anti-HIV-1/AIDS drugs, their mechanisms of action, and possible management strategies to combat this problem.

Keywords: HIV-1, AIDS, anti-HIV-1RT drugs, antiproteases, anti-integrases, fusion inhibitors, dosage, toxicity, management

Download Article [PDF] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Other article by this author:

Readers of this article also read:

Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors

Eduardo Pimenta, Suzanne Oparil

Vascular Health and Risk Management 2009, 5:453-463

Published Date: 19 May 2009

Exploring patients’ perceptions for insulin therapy in type 2 diabetes: a Brazilian and Canadian qualitative study

Camila Guimarães, Carlo A Marra, Sabrina Gill, et al

Patient Preference and Adherence 2010, 4:171-179

Published Date: 29 June 2010

The use of anti-tuberculosis therapy for latent TB infection

Justin T Denholm, Emma S McBryde

Infection and Drug Resistance 2010, 3:63-72

Published Date: 21 July 2010

Progress in antiretroviral drug delivery using nanotechnology

Rama Mallipeddi, Lisa Cencia Rohan

International Journal of Nanomedicine 2010, 5:533-547

Published Date: 22 July 2010

Development of neurocognitive disorders in HIV/AIDS

Brandon C Dennis, Sidney A Houff, Dong Y Han, et al

Neurobehavioral HIV Medicine 2011, 3:9-18

Published Date: 10 March 2011

The neuro-ophthalmology of HIV-AIDS review of Neurobehavioral HIV Medicine

Sudhakar P, Kedar S, Berger JR

Neurobehavioral HIV Medicine 2012, 4:99-111

Published Date: 18 September 2012