Lamivudine or stavudine in two- and three-drug combinations against human immunodeficiency virus type 1 replication in vitro.
Two- and three-drug combinations of lamivudine or stavudine with other antiretroviral drugs were evaluated for activity against human immunodeficiency virus type 1 (HIV-1) activity in peripheral blood mononuclear cells. Other agents included zidovudine, didanosine, nevirapine, and saquinavir. Paired zidovudine-sensitive and -resistant clinical HIV-1 isolates were used. Additive or synergistic interactions were observed against the zidovudine-sensitive isolate with the following combinations: lamivudine-zidovudine, lamivudine-stavudine, lamivudine-saquinavir, lamivudine-nevirapine, stavudine-zidovudine, stavudine-didanosine, stavudine-saquinavir, stavudine-nevirapine, lamivudine-zidovudine-saquinavir, lamivudine-zidovudine-stavudine, stavudine-zidovudine-nevirapine, lamivudine-zidovudine-nevirapine, and stavudine-zidovudine-saquinavir. Against the zidovudine-resistant isolate, additive or synergistic interactions were seen with most two- and three-drug combinations, but the combination of stavudine-zidovudine was antagonistic. The clinical implications of these in vitro observations should be explored.
Merrill
D P
DP
Infectious Disease Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Moonis
M
M
Chou
T C
TC
Hirsch
M S
MS
D000998:Antiviral Agents / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D054303:HIV Reverse Transcriptase; D006679:HIV Seropositivity / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D018119:Stavudine / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000998:Antiviral Agents; D004338:Drug Combinations; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D016047:Zalcitabine; D018119:Stavudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase