Polymorphisms in HIV-1 subtype C proteases and the potential impact on protease inhibitors.
OBJECTIVE
(i) To review data on the genetic profile of the protease (PR) gene of human immunodeficiency virus (HIV)-1-C primary isolates relative to HIV-1-B; (ii) to examine data on the susceptibility of HIV-1-C isolates harbouring polymorphisms to PR inhibitors (PI) and the development of resistance; and (iii) to identify gaps required for an improved understanding of the role of polymorphisms in resistance development of HIV-1-C to PI.


METHODS
Literature review.


RESULTS
Significant differences exist between the baseline nucleotide and amino acid sequences of PR of HIV-1-B and HIV-1-C. Some of the amino acid substitutions seen in HIV-1-B when exposed to PI occur naturally in HIV-1-C isolates. Studies used different methodologies and interpretation systems to evaluate the phenotypic significance of polymorphisms seen in subtype C viruses, with conflicting outcomes. The evolutionary path to the resistance of HIV-1-C to PI may be different from that of HIV-1-B.


CONCLUSIONS
Infection with HIV-1-C is driving the AIDS epidemic in regions of the world with the most urgent needs for the management of the disease. More and more individuals will require PR inhibitors in second-line therapies, as access to antiretrovirals progresses. It is proposed that a standardized protocol be adopted to evaluate the phenotypic significance of the highly polymorphic HIV-1-C PR to PR inhibitors with the aim of better informing the tailoring of treatment regimens for optimal clinical benefit.
Bessong
Pascal Obong
PO
University of Venda, Thohoyandou, South Africa. bessong@univen.ac.za
D019943:Amino Acid Substitution; D024882:Drug Resistance, Viral / Q000235:genetics*; D014644:Genetic Variation; D015658:HIV Infections / Q000453:epidemiology / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000145:classification / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D017720:Molecular Epidemiology; D011110:Polymorphism, Genetic; D017211:Treatment Failure
D017320:HIV Protease Inhibitors; D016333:HIV Protease