ADS-J1 inhibits HIV-1 entry by interacting with gp120 and does not block fusion-active gp41 core formation.

We had shown that virus resistance to ADS-J1 was associated with amino acid changes in the envelope glycoprotein, mostly located in the gp120 coding region. Time-of-addition and endocytic virus transfer assays clearly demonstrated that ADS-J1 behaved as a gp120 inhibitor. ADS-J1-resistant virus was cross-resistant to the polyanion dextran sulfate, and recombination of gp120 recovered only the ADS-J1-resistant phenotype.

Different selection patterns of resistance and cross-resistance to HIV-1 agents targeting CCR5.

Objectives: Identification of CCR5 as an antiretroviral target led to the development of several CCR5 antagonists in clinical trials and the approval of maraviroc. Evaluating the mechanism of drug resistance to CCR5 agents may have implications in the clinical development of this class of agents. We have analysed the resistance profile of two R5 HIV-1 strains [BaL and a clinical isolate (CI)] after long-term passage in cell culture in the presence of TAK-779, the first developed non-peptidic small molecule targeting CCR5.