Analysis of HIV-1 CRF_01 A/E protease inhibitor resistance: structural determinants for maintaining sensitivity and developing resistance to atazanavir.

A series of HIV-1 protease mutants has been designed in an effort to analyze the contribution to drug resistance provided by natural polymorphisms as well as therapy-selective (active and non-active site) mutations in the HIV-1 CRF_01 A/E (AE) protease when compared to that of the subtype B (B) protease. Kinetic analysis of these variants using chromogenic substrates showed differences in substrate specificity between pretherapy B and AE proteases. Inhibition analysis with ritonavir, indinavir, nelfinavir, amprenavir, saquinavir, lopinavir, and atazanavir revealed that the natural polymorphisms found in A/E can influence inhibitor resistance.

Sequence variability of the HIV type 1 protease gene in thai patients experienced with antiretroviral therapy.

One hundred sequences of HIV-1 protease with the two flanking cleavage sites from 10 antiretroviral drug-treated Thai patients were examined for residue variability and for mutations at positions associated with the resistance to protease inhibitors. Seven patients were infected with CRF01_AE, two with subtype B, and one with a strain that did not belong to any of the currently identified subtypes or recombinant forms. A total of 46 out of the 99 positions (46%) in HIV-1 protease showed at least one amino acid change as compared with the HXB2 subtype B protease.