Protease inhibition in African subtypes of HIV-1

Adrián Velázquez-Campoy, Sonia Vega, Erin Fleming, Usman Bacha, Yasien Sayed, Heini W. Dirr, Ernesto Freire

Research output: Contribution to journalReview articlepeer-review

Abstract

Of the 42 million people infected with HIV-1 worldwide, 30 million are in Africa. However, the HIV-1 subtypes prevalent in Africa are not the same that are prevalent in North America and Western Europe. In these developed regions, subtype B is responsible for the vast majority of HIV infections, whereas in sub-Saharan Africa subtypes A and C, and to a lesser extent subtype G, account for most of the infections. These subtypes exhibit genomic differences as large as 30% with respect to subtype B. These differences involve current drug targets, including the HIV-1 protease. Since protease inhibitors have been developed and tested against the HIV-1 B subtype, and proteases from other subtypes carry up to ten amino acid polymorphisms, it is important to assess the influence of these naturally occurring polymorphisms on the potency of existing inhibitors, as well as their synergistic interactions with mutations known to cause drug resistance. This review will examine the effects of naturally occurring polymorphisms on the efficacy of current protease inhibitors and the effects of well characterized drug-resistant mutations within the framework of non-B subtypes. At the biochemical level, non-B-subtype polymorphisms lower the binding affinities of existing clinical inhibitors, but not to the point of causing drug resistance. However, these polymorphisms amplify the effects of mutations causing drug resistance and may play a role in the long-term viability of these inhibitors.

Original languageEnglish (US)
Pages (from-to)165-171
Number of pages7
JournalAIDS Reviews
Volume5
Issue number3
StatePublished - Jul 1 2003

Keywords

  • AIDS
  • Africa
  • Calorimetry
  • Drug resistance
  • Non-B subtypes
  • Protease inhibitors

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Protease inhibition in African subtypes of HIV-1'. Together they form a unique fingerprint.

Cite this