[The in vitro HAART pharmacodynamics study with dolutegravir as the "anchor"].
This study is to evaluate the HAART pharmacodynamics with dolutegravir as the "anchor" in vitro. A nucleoside reverse transcriptase inhibitors (NRTIs) resistant recombinant virus model (VSVG/HIV-1(RT-D67N,K70R,T215F)) and an integrase inhibitors (INIs) resistant recombinant virus model (VSVG/HIV-1(IN-G140S,QI48H)) were constructed and established. The anti-viral pharmacodynamics was evaluated with drug combinations including two NRTIs along with one INI or one NNRTI. The results showed that the combination with an INI gave a stronger synergism on wild type HIV-1 replication comparing to that with an NNRTI. Comparing the two INIs as the "anchor" for HAART, DTG exhibited an equivalent CI to that of RAL on wild type HIV-1 replication; but a greater synergy than RAL on INI-resistant HIV-1 replication. Besides of the pharmacodynamics results of DTG-based drug combination, the results may contribute to clinical antiviral therapy.
Jia-mei
JM
Guo
Ying
Y
Guo
D023241:Antiretroviral Therapy, Highly Active; D002478:Cells, Cultured; D024882:Drug Resistance, Viral; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D006801:Humans; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D014779:Virus Replication / Q000187:drug effects; D000099226:Dolutegravir
D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D000099226:Dolutegravir