Isolation and Molecular Characterization of a Nelfinavir (NFV)-Resistant Human Immunodeficiency Virus Type 1 That Exhibits NFV-Dependent Enhancement of Replication

Broad Antiretroviral Activity and Resistance Profile of the Novel Human Immunodeficiency Virus Integrase Inhibitor Elvitegravir (JTK-303/GS-9137)

“…These results indicate that mutations associated with resistance to IN inhibitors can have various effects on viral replication capacity. The reduced replication capacity of EVG-resistant variants was not rescued in the presence of the inhibitor (data not shown), as was observed previously for NFV-resistant variants in the presence of NFV (35). Thus, the reduced replication capacity of IN inhibitorresistant variants may present a barrier to their emergence in vivo.…”

Azido-Containing Diketo Acid Derivatives Inhibit Human Immunodeficiency Virus Type 1 Integrase In Vivo and Influence the Frequency of Deletions at Two-Long-Terminal-Repeat-Circle Junctions

“…It is conceivable that because the T66I/ S153Y mutations of HIV-1 IN were selected in the presence of a DKA, the geometry of the active site of the drug-resistant enzyme is optimal for catalysis only when a DKA is bound to HIV-1 IN. The phenomenon of drug-dependent viral replication has been previously described (47); these studies also suggest that viruses containing drug resistance mutations evolved to enhance viral replication in the presence of the drug. The azido-containing DKAs could serve as useful tools for understanding the mechanisms by which these drug-resistant variants replicate more efficiently in the presence of the DKAs, the mechanisms by which DKAs inhibit HIV-1 integration, and the mechanisms of viral drug resistance.…”

HIV‐1 Proteases from Drug‐Naive West African Patients Are Differentially Less Susceptible to Protease Inhibitors

“…Second, our drug assay was performed simply by utilizing protease-cassette vector viruses carrying only patient-derived protease genes, although several studies have suggested that the PI susceptibility is affected, not only by changes in the protease per se, but also by changes in other regions, such as p1/p6 gag and p17 gag [35,36]. Therefore, we also constructed a recombinant virus clone (pNL-Luc-AG2gp; see Patients and Methods) that harbored an A/G recombinant-derived gag-pol gene and tested its drug susceptibility.…”