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HIV-1 resistant to protease inhibitors in vitro due to one point mutation in pol gene.




 

Int Conf AIDS. 1994 Aug 7-12;10(2):115 (abstract no. PA0339). Unique

OBJECTIVE: To study the possibility of emergence of HIV-1 strains resistant to protease inhibitors and explore the mechanism of resistance. METHODS: A. An HIV-1 clone was maintained in gradually increasing doses of a protease inhibitor in vitro. The resulting resistant mutant was characterized in terms of: 1) sensitivity to the agent; 2) infectivity and cytopathogenicity; 3) genetic changes in gag and pol genes. B. An HIV-1 infectious DNA clone with the detected point mutation in pol gene was constructed and also characterized. RESULTS: 1) The resistant mutant had one point mutation in pol gene resulting in one amino acid change in the protease enzyme. 2) The DNA infectious clone having this point mutation was also resistant to the protease inhibitor. 3) This point mutation resulted in a significant loss of the virus infectivity and cytopathogenicity. CONCLUSION: 1) HIV-1 will be able to escape the effect of protease inhibitors by just one point mutation, so combined therapy must be used in vivo. 2) There is a relation between HIV-1 protease structure and its acute infectivity.

Cytopathogenic Effect, Viral/GENETICS Drug Resistance, Microbial/GENETICS Drug Therapy, Combination Genes, gag *Genes, pol Human HIV Infections/DRUG THERAPY HIV Protease Inhibitors/ADMINISTRATION & DOSAGE/*PHARMACOLOGY HIV-1/*DRUG EFFECTS/*GENETICS/PATHOGENICITY In Vitro Point Mutation Virulence/GENETICS/PHYSIOLOGY ABSTRACT



 




Information in this article was accurate in December 30, 1994. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.