Polymorphism in HIV-1 non-subtype B protease and reverse transcriptase and its potential impact on drug susceptibility and drug resistance evolution.
HIV-1 non-subtype B viruses are predominant worldwide. At least 9 different HIV-1 group M subtypes and 14 circulating recombinant forms differ from one another by 10-15% in their pol gene, which includes the coding regions for the viral protease and reverse transcriptase (RT), the current targets of antiretroviral drugs. Inter-subtype genotypic diversity includes polymorphism at amino acid residues known to be related to drug resistance in HIV-1 subtype B. Whether polymorphism alters protease and RT function, drug susceptibility, or clinical response to treatment, is unclear. Worldwide dissemination of non-subtype B viruses and increasing availability of antiretroviral drugs in the developing world will expand drug use and the likelihood of drug resistance in non-subtype B viruses. In this review we define and characterize inter-subtype RT and protease polymorphism, and examine the evidence for genotypic and phenotypic differences between HIV-1 subtypes as well as the potential for different clinical responses and evolution of drug resistance among non-B infected individuals.
Kantor
Rami
R
Division of Infectious Diseases and AIDS Research, Stanford University, Stanford, CA, USA. rkantor@stanford.edu
Katzenstein
David
D
D019380:Anti-HIV Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000235:genetics*; D019143:Evolution, Molecular; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease