Md. Oh et al., SEQUENTIAL VERSUS SIMULTANEOUS COMBINATION ANTIRETROVIRAL REGIMENS FOR THE TREATMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION IN-VITRO, The Journal of infectious diseases, 176(2), 1997, pp. 510-514
Two-, three-, and four-drug antiretroviral combinations in either simu
ltaneous or sequential regimens were evaluated for their ability to su
ppress human immunodeficiency virus (HIV) type 1 replication in vitro.
Zidovudine, lamivudine, saquinavir, and nevirapine were used at IC(90
)s, IC(99)s, or IC(greater than or equal to 99)s in a CD4-positive hum
an lymphoblastoid cell line (H9 cells) acutely infected with HIV-1. In
sequential regimens, drugs were added at weekly intervals. In simulta
neous regimens, all drugs were added on day 0. Increasing the number o
f drugs in a combination regimen both increased the degree of viral in
hibition and delayed the time of breakthrough viral replication. Simul
taneous regimens provided more profound and earlier viral inhibition t
han did sequential regimens. However, sequential addition provided rel
atively more durable viral inhibition than did simultaneous regimens w
hen drug concentrations were low. The relative effectiveness of differ
ent HIV-1 therapeutic strategies depends on both the numbers and conce
ntrations of the drugs used.