Lack of antagonism between abacavir, lamivudine, and tenofovir against wild-type and drug-resistant HIV-1.
Potential contributors to the high rate of virologic failure observed for tenofovir, abacavir, and lamivudine include a low genetic barrier to resistance for this regimen and antagonistic drug-drug interactions. To examine the second possibility, we tested combinations of abacavir, tenofovir, and lamivudine against wild-type and drug-resistant HIV-1 in vitro using peripheral blood mononuclear cells and MT-4 cells. Antagonistic interactions were not detected for any combination. If the systems examined accurately reflect the in vivo situation, antagonism does not substantially contribute to the poor efficacy of this triple combination.
Lanier
E Randall
ER
GlaxoSmithKline, Research Triangle Park, NC 27705, USA. ernest.r.lanier@gsk.com
Hazen
Richard
R
Ross
Lisa
L
Freeman
Andy
A
Harvey
Robert
R
D000225:Adenine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002461:Cell Line, Transformed; D015224:Dideoxynucleosides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009154:Mutation; D063065:Organophosphonates / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000068698:Tenofovir; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D019259:Lamivudine; D063065:Organophosphonates; D000068698:Tenofovir; D000099227:Abacavir