Polymorphisms in HIV-1 subtype C proteases and the potential impact on protease inhibitors

Abstract

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.