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Polymorphisms in HIV‐1 subtype C proteases and the potential impact on protease inhibitors
Author(s) -
Bessong Pascal Obong
Publication year - 2008
Publication title -
tropical medicine and international health
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.056
H-Index - 114
eISSN - 1365-3156
pISSN - 1360-2276
DOI - 10.1111/j.1365-3156.2007.01984.x
Subject(s) - protease , human immunodeficiency virus (hiv) , biology , virology , proteases , phenotype , drug resistance , single nucleotide polymorphism , virus , genetics , gene , medicine , genotype , enzyme , biochemistry
Summary Objectives (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. Method 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.