Journal of Analytical & Bioanalytical Techniques
Open Access

Abstract

The emergence of drug resistance variants has been the main stumbling blockade to the favorable clinical outcome of chemotherapy. The resistance to one drug often results in cross-resistance to many, if not all, others in the same class. Failure of the current HAART regimen due to drug resistance can severely limit second-line, third-line, and salvage treatment options. The prime causes of drug resistance primarily include the inadequate exposure of the virus to antiretroviral agents, poor adherence to complicated regimens and variability in drug pharmacokinetics. A number of mutations due to application of almost all therapeutic antiHIV-1 drugs especially with nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), anti-proteases and/or a combination of these regimens such as HAART have been selected into different regions of pol gene of HIV-1 encoding the viral enzymes (HIV-1RT, protease and integrase). These mutations alter the function of the target proteins of HIV-1, thus allowing the virus to replicate efficiently even in the presence of antiretroviral agents. Very recently, it is known that these compounds also induce emergence of a compensatory mutation, which is found to be located far from the active site of the enzyme protein. It repairs the functions of altered protein in a way that helps return them back to near normal. It is presumed that these mutations influence the activity of the enzyme by inducing conformational flexibility; however, the detailed mechanistic aspect of this event is still unclear. The present paper includes molecular mechanisms involved in anti-HIV-1 drugs resistance, the development of new drugs that could be active against antiHIV-1 drugs resistant mutants, new targets for effectively arresting the viral replication in human cells and other strategies to combat the scourge.

Biography

Bechan Sharma has completed his Ph.D. from Banaras Hindu University-Varanasi and Central Drug Research Institute-Lucknow, India in 1988. He has been visiting scientist fo three years at University of Medicine and Dentistry of New Jersey-NJ Medical School, Newark, USA (2000-2002); and as a Visiting Professor for two to four months at Italy, France, Thailand, Brazil, Germany and other countries. He is currently working as a senior Professor and Ex-Chairman of Departments of Biochemistry and Biotechnology at the University of Allahabad, a premier Central University of India. He has published more than 90 research papers in peer reviewed international journals of repute and one US patent to his credit. His Book on `Recent Trends in Biotechnology` has been published in two volumes by Nova Publishers-NY, USA. He is on the reviewer panel of 65 International / National Journals and working as Chief-Editor/ Guest Editor/ Associate Editorial / Member Editorial Board of 26 International/ National journals. He has produced 10 Ph.D. students in different areas of Biochemistry/Molecular Biology.